Diagnostic Approach To Children and Adolescents With Short Stature

Diagnostic approach to children and adolescents with short stature - UpToDate 25/07/21 06.
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Diagnostic approach to children and adolescents with short stature

Authors: Erick J Richmond, MD, Alan D Rogol, MD, PhD
Section Editor: Mitchell E Geffner, MD
Deputy Editor: Alison G Hoppin, MD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jun 2021. | This topic last updated: May 11, 2021.
INTRODUCTION
Short stature is defined as a height that is 2 standard deviations (SD) or more below the mean height for individuals of the same sex and
chronologic age in a given population. This translates to a height that is below the 2.3rd percentile.
The most common causes of short stature beyond the first year or two of life are familial (genetic) short stature and constitutional short stature
(also known as constitutional delay of growth and puberty [CDGP]), which are normal nonpathologic variants of growth. These growth patterns
often can be distinguished from one another, but some children have features of both (see "Causes of short stature", section on 'Normal variants
of growth'). The goal of the evaluation of a child with short stature is to identify the subset of children with pathologic causes, such as Turner
syndrome, inflammatory bowel disease or other underlying systemic disease, or hormonal abnormality. The evaluation also assesses the severity
of the short stature and likely growth trajectory to facilitate decisions about intervention, if appropriate. Some components of the evaluation can
reasonably be performed in the primary care setting, including initial interpretation of the growth chart and growth potential (based on
measured heights of the child's parents), calculation of height velocity (HV), and initial laboratory screening for an underlying systemic or
endocrine disease, if suspected based on symptoms. If HV is slow, then bone age determination should be performed, if expert interpretation is
available. Other components of the evaluation, including review of the bone age results and the detailed evaluation for causes of short stature,
are typically performed by a pediatric endocrinologist, if available.
Referral patterns reveal substantial sex differences in the evaluation and treatment of children with short stature [1-4]. Boys are referred for
evaluation more often, at younger ages, and for less severe height deficits compared with girls. As an example, in one retrospective review of 288
children referred to a single center for assessment of short stature, the male:female ratio was 1.9:1 [1]. At the time of referral, the height deficit
was significantly greater for girls than boys (median height Z-score -2.4 versus -1.9) and organic disease was more common among girls (40
versus 15 percent). Similarly, studies of growth hormone registries have shown preferential treatment of boys compared with girls with an
approximate ratio of 2:1 [2,3,5].
This apparent gender bias may be due to underappreciation of growth problems in girls, leading to fewer evaluations of girls for short stature.
Alternatively, it may be due to increased societal pressure for tall stature in boys, leading to increased referral and growth hormone treatment of
boys without organic causes of short stature. These findings emphasize the need for accurate growth monitoring during the health care
maintenance of all children to ensure appropriate referral and treatment.
This topic will review the diagnostic approach to children with short stature, beginning with a brief review of normal growth and development.
The causes of short stature are discussed separately. (See "Causes of short stature".)
NORMAL GROWTH
Serial measurements of growth are an important parameter in monitoring the health of children. A normal pattern of growth usually suggests
good general health, while growth that is slower than normal raises the possibility of an underlying subacute or chronic illness, including an
endocrinologic cause of growth failure.
Statural growth is a continuous but not linear process. There are three phases of postnatal growth (infantile, childhood, and pubertal), each of
which has a distinctive pattern [6]. The phases are similar for boys and girls, but the timing and pace of growth differ, particularly during puberty.
● Intrauterine – Size at birth is determined more by maternal nutrition and intrauterine and placental factors than by genetic makeup. Not all
the genes that affect growth may be expressed at birth. As a result, the correlation coefficient between birth length and adult height is only
0.25 [7].
● Infancy – During the first two years of life (infantile phase), linear growth initially is very rapid and gradually decelerates. Overall growth
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Diagnostic approach to children and adolescents with short stature - UpToDate 25/07/21 06.41
during this period is approximately 30 to 35 cm. The length (and weight) of premature infants must be corrected for gestational age, at least
for the first year. However, growth is often accelerated during the second one-half of the first year in otherwise healthy children born early.
An infant's height curve often crosses percentile lines during the first 24 months of life as the growth moves away from the influences of the
intrauterine environment and toward the child's genetic potential. As examples, infants born small because of placental or uterine constraint
may move upwards across percentile curves ("channeling up"), whereas infants born large because of maternal-fetal overnutrition may cross
downward across percentile curves ("channeling down"). After this adjustment period, the correlation between length at two years and adult
height is 0.80 [7].
● Childhood – The childhood phase is characterized by linear growth at a relatively constant velocity, with some slowing in later childhood.
Most children grow at the following rates (representing the 10th to 90th percentiles):
• Age two to four years – 5.5 to 9 cm/year (2.2 to 3.5 inches/year)

• Age four to six years – 5 to 8.5 cm/year (2 to 3.3 inches/year)
• Age six years to puberty:
- 4 to 6 cm/year for boys (1.6 to 2.4 inches/year)
- 4.5 to 6.5 cm/year for girls (1.8 to 2.6 inches/year)
● Adolescence – The pubertal phase is characterized by a growth spurt of 8 to 14 cm per year due to the synergistic effects of increasing
gonadal steroids and growth hormone [8]. In girls, the pubertal growth spurt typically starts around age 10 but may start as early as age 8
for early maturing girls. In boys, the pubertal growth spurt typically starts around age 12 but may start as early as age 10 in early maturing
boys [9].
The "rule of fives" incorporates these typical phases of growth and provides an estimate for normal height and height velocity (HV) in a given age
group, as shown in the table ( figure 1). Actual height and HV in a healthy child can vary substantially around these approximations.
EVALUATION OF GROWTH
Evaluation of a child suspected of having short stature is guided by answering the following questions. Although the causes and clinical
presentation of short stature vary by age group, the same questions are relevant for children of any age:
● How short is the child?

● Is the child's height velocity (HV) impaired?
● What is the child's likely (predicted) adult height?
The answers to these questions guide a focused history and physical examination and, in some cases, laboratory evaluation to determine the
cause(s) and appropriate management of the child with short stature ( algorithm 1).
Is the child short? — Accurate measurement of length or height is essential; inaccurate measurements or aberrant plotting is one of the more
common causes of apparent growth failure. Length is measured lying down and should be used for infants and children up to 24 months of age;
height is measured standing and should be used for children two years and older (if possible) ( figure 2).
● Standard approach using height-for-age growth curves – The child's length or height should be plotted on the growth chart that is
appropriate for the child's age and gender (children <24 months ( figure 3A-B); children two years and older ( figure 4A-B)). Weight
should also be measured to provide additional information about the child's nutritional status. (See "Measurement of growth in children".)
Percentiles and Z-scores can be calculated using a calculator for recumbent length (calculator 1) or standing height for boys (calculator 2) or
for girls (calculator 3). For the purposes of an endocrine evaluation, short stature is defined as a length or height more than 2 standard
deviations (SD) below the mean (ie, a Z-score <-2), which corresponds to a height that is <2.3rd percentile.
• Height above the 2.3rd percentile (>-2 SD) – These children generally do not require further specific evaluation unless there are additional
reasons for concern, such as progressively decreasing height percentiles (implying growth failure), dysmorphic features, or evidence of
underlying systemic disease, or if they are growing well below their genetic potential (eg, they are children of very tall parents).
• Height below the 2.3rd percentile (≤-2 SD) – These children have short stature and should undergo a more detailed evaluation, starting
with evaluation of HV, as outlined in the following sections. The first steps of this evaluation usually can be performed in the primary
care setting. Early referral to a specialist is appropriate if the HV is very slow.
• Height less than the 1st percentile (≤-2.25 SD) – These children have extreme short stature and usually should be referred to an
appropriate subspecialist for a detailed evaluation, where available. The first steps in the evaluation will be similar, but a higher index of
suspicion for pathologic causes of growth faltering is appropriate.
●Tanner-stage-adjusted (TSA) growth curves (for selected patients) – For children with late puberty for their age (including those whose
puberty is delayed because of medical illness or puberty-suppressing therapy), use of standard height-for-age growth references may exaggerate
the child's degree of short stature. For these children, growth potential may be more accurately assessed by using special TSA growth standards,
which are captured in this online calculator or by plotting the child's growth on a TSA-adjusted growth curve, selected for their stage of pubertal
development (sexual maturity rating) [10].
Is the child's height velocity impaired? — Determination of the child's HV is an essential component of the evaluation of a child for short
stature and can be considered a "vital sign" ( algorithm 1). This requires serial measurements of height, which should be measured along with
weight at each well-child visit. Serial measurements help to determine whether the child's HV is within normal range and whether it progressively
deviates from its previous growth channel (or percentile curve). The HV should be calculated (in cm/year) using accurate measurements of height
and an interval between measurements of at least six months. Plotting height and HV immediately after the measurement is taken on the child's
growth chart is important because this may help identify a measurement error and permit remeasurement. The data can be easily plotted using
the growth charts included in an electronic health record.
For children two years and older, growth failure is likely if:
● The height-for-age curve has deviated downward across two major height percentile curves (eg, from above the 25th percentile to below the
10th percentile).
● Or, if the child is growing slower than the following rates:
• Age two to four years – HV less than 5.5 cm/year (<2.2 inches/year)
• Age four to six years – HV less than 5 cm/year (<2 inches/year)
- HV less than 4 cm/year for boys (<1.6 inches/year)
- HV less than 4.5 cm/year for girls (<1.8 inches/year)
Short children with HV above these cut points usually have a nonpathologic cause of short stature, such as familial short stature or constitutional
delay of growth. For these children, a basic evaluation for short stature usually is sufficient, consisting of a focused history, physical examination,
adult height prediction, and bone age determination, as outlined in the following sections [11]. (See 'Prediction of adult height' below and 'Bone
age determination' below.)
Short children with HV below these cut points are more likely to have a pathologic cause of short stature and warrant additional attention. In
addition to the basic evaluation outlined above, laboratory screening for pathologic causes of growth failure is warranted. The clinician should be
particularly alert for subtle symptoms of underlying systemic disease (eg, Crohn disease) and for evidence of Turner syndrome in girls [11,12].
The detailed evaluation may be most appropriately performed by a pediatric endocrinologist, if available. (See 'Laboratory and imaging studies'
below.)
Short children with HV substantially below these cut points are most likely to have a pathologic cause of short stature and should undergo a
detailed evaluation for pathologic causes of growth failure by a pediatric subspecialist, if available.
Alternatively, for a more precise assessment, the child's HV can be plotted on an HV chart ( figure 5A-B) to determine the HV percentile (or SD
[Z-score]) for the child's age and gender (note that this is different from the height-for-age percentile). In general, HV between the 10th and 25th
percentile should raise concern for possible growth failure and an HV below the 10th percentile warrants a thorough evaluation for growth
failure.
Prediction of adult height — Adult height is determined by a combination of genetic potential and many other factors that influence somatic
growth and biologic maturation. No method accurately predicts adult height, and there is wide variation in predicted adult height among the
different methods. However, an estimate of adult height can be developed using information about heights in the biologic family, combined with
information about the child's own growth and level of skeletal development. The results help to guide decisions about evaluation and treatment
and also provide some information about the possible causes of short stature in a particular patient.
Is the child's growth within the range for the family? — The next step is to determine the height range expected for the child's biologic
family and compare it with the child's growth trajectory. In most populations, a predicted adult height that is <63 inches (160 cm) for men and
<59 inches (150 cm) for women is considered short stature, corresponding to more than 2 SD below the mean (<2.3rd percentile) for adults of the
same population and gender.
● Midparental height – An estimate of a child's genetic height potential can be obtained by calculation of the midparental height, which is
based upon the heights of both parents and adjusted for the sex of the child ( algorithm 1). This estimate is also known as the "target
height." Whenever possible, the parents' heights should be directly measured rather than self-reported. The calculation can be performed
using a calculator (calculator 4) or the following equation:
• For girls, 13 cm (or 5 inches) is subtracted from the father's height and averaged with the mother's height
• For boys, 13 cm (or 5 inches) is added to the mother's height and averaged with the father's height
• For both girls and boys, 8.5 cm (3.3 inches) on either side of this calculated value (target height) represents the 3rd to 97th percentiles for
anticipated adult height [13]
In this calculation, the 13 cm (or 5 inches) represent the average difference in the average height of adult men and women. Thus, the child
grows, on average, to the midparental height percentile.
If there is a large discrepancy between parents' heights, with one very short parent, the possibility of a dominantly inherited disorder should
be considered, perhaps within a gene affecting the growth plate [14,15]. (See "Causes of short stature", section on 'Genetic diseases with
primary effects on growth'.)
● Projected height – The projected height for a child older than two years is determined by extrapolating the child's growth along the current
channel to the 18- to 20-year mark ( figure 6). If the child's bone age is delayed or advanced, then the projected height should be plotted
based on the bone age rather than the chronologic age. (See 'Bone age determination' below.)
The child's projected height is then compared with the range calculated from the midparental (target) height.
● If the child's projected height is within 8.5 cm (2 SD) of the midparental height, then the child's height is within the expected range for the
family. This child probably has familial short stature, which is considered a variant of normal growth. (See "Causes of short stature", section
on 'Familial short stature'.)
● If the projected height is more than 8.5 cm (2 SD) below the midparental height, then the child can be considered abnormally short for his or
her family.
Is there evidence of delayed or accelerated growth? — Most children with severe short stature (height <-2.25 SD) or growth failure should
undergo a radiographic determination of bone age. This helps to determine whether the child's growth is delayed or accelerated compared with
his or her chronologic age.
Bone age determination — Bone age (also known as skeletal age) is typically determined from a radiograph of the left hand and wrist and
requires expert interpretation. The methods used most commonly for determining skeletal age are the Greulich and Pyle Atlas [16] and the
Tanner-Whitehouse 3 (TW3) method [17]. In general, TW3 is considered to be more accurate, based on studies in predominantly White European
populations [18]. However, bone ages obtained from these methods are less generalizable to other groups of children; Black or African American
children tend to have advanced bone age, and Southeast Asian children tend to have delayed bone age, compared with their White peers [19,20].
The bone age determination informs estimates of the child's growth potential and likely adult height, as follows:
● Delayed or advanced bone age is defined as a bone age that is 2 SD or more below or above the mean, respectively. This is approximately 20
percent below or above the chronologic age. This translates to a difference between bone age and chronologic age of approximately 12
months between 2 and 4 years of chronologic age, 18 months between 4 and 12 years, and 24 months after age 12 ( figure 7A-B). If the
bone age is delayed or advanced near or beyond these parameters, then the projected height should be recalculated based on the bone age
rather than the chronologic age. This will provide a more accurate assessment of projected height. As an example, if an eight-year-old boy is
117 cm tall and has a bone age of 6.5 years, this corresponds to the 3rd percentile for chronologic age but to the 35th percentile for skeletal
age, suggesting that the child may have constitutional delay of growth.
● The bone age can be used to predict the child's adult height. The technique developed by Bayley-Pinneau (BP) is most commonly used for
children approximately six years and older [21]. This technique employs a table to translate the child's bone age and chronologic age to a
decimal fraction of adult height (eg, 0.75). To predict adult height, the present height is divided by the fraction of adult height.
Other methods use different algorithms to predict adult height from height measurements and bone age data and include the TW3, Roche-
Wainer-Thissen (RWT), and Khamis-Roche (KR) methods. RWT and KR incorporate midparental height in addition to bone age, and TW3 uses
a skeletal maturity score. Comparison of these methods reveals a wide range of adult height predictions. Overall, the TW3 method (or the
previous version, TW2) either underpredicts or overpredicts adult height in approximately 30 percent of individuals [22,23], while the BP and
RWT methods tend to overpredict adult height in boys [24]. The BP method is most likely to identify a short child as a candidate for growth
hormone therapy [25]. Methods that incorporate bone age are generally more accurate in predicting adult height than the simple
midparental height method. However, there is a wide variation in height prediction, and the same method may yield significantly different
adult height predictions at different ages [24].
The results of the bone age determination also provide important information about possible causes of the short stature ( algorithm 1):
● A significantly delayed bone age is consistent with constitutional delay of growth and puberty (CDGP), which is considered a variant of
normal growth. However, significantly delayed bone age is also seen in many types of pathologic growth failure, including nutritional
deficiency, underlying systemic disease (such as inflammatory bowel disease), and growth hormone deficiency. The HV helps to distinguish
between these categories: Children with CDGP tend to have normal or low-normal HV until they reach bone age of 11 years in girls or 13
years in boys. By contrast, children with underlying systemic or endocrine disease tend to have progressive decreases in HV. Children with
significantly delayed bone age should undergo a focused history and physical examination to evaluate for symptoms and signs of systemic
or endocrine disease (see 'Additional evaluation for causes of short stature' below). Their growth should also be carefully monitored.
● A normal bone age is consistent with several diagnostic possibilities: In a child with short parents, a normal bone age supports the diagnosis
of familial short stature. However, a normal bone age is also seen in younger girls with Turner syndrome. Moreover, bone age may be only
mildly delayed in early or mild forms of some of the systemic diseases that cause growth failure. Therefore, a bone age that is within normal
limits suggests that underlying genetic or systemic disease is unlikely but not impossible.
● Advanced bone age is occasionally seen in older children and adolescents with short stature, especially those with precocious puberty and
hyperthyroidism. These children usually experience accelerated early growth but are at risk for early epiphyseal closure, resulting in short
stature as an adult if not properly diagnosed and treated. Children with autosomal dominant short stature due to aggrecan mutations also
have short stature with advanced bone age [26]. (See "Causes of short stature", section on 'Sexual precocity' and "Causes of short stature",
section on 'Skeletal dysplasias/growth plate abnormalities'.)
ADDITIONAL EVALUATION FOR CAUSES OF SHORT STATURE
In addition to the evaluation of growth outlined above, a focused history and physical examination contribute information that helps to
categorize the cause of short stature ( table 1 and algorithm 1). The key information is organized here according to the diagnostic category
of the short stature. Further details about each cause of short stature are presented in the linked topic review. (See "Causes of short stature".)
Are there features that suggest that this is a normal variant of short stature? — The two most common causes of short stature are familial
(genetic) short stature and constitutional delay of growth and puberty (CDGP; also termed constitutional short stature for prepubertal children).
These growth patterns often can be distinguished from one another, but some children have features of both ( table 2). Unless there are signs
or symptoms of underlying disease, children with these growth patterns usually require only a basic evaluation, including a focused history,
physical examination, and bone age determination. (See 'Laboratory and imaging studies' below.)
● In familial short stature, height velocity (HV) and bone age are within the normal range and one or both parents are short. (See "Causes of
short stature", section on 'Familial short stature'.)
● In CDGP, the child's growth rate is appropriate for his or her bone age, which is delayed compared with chronologic age. If the height is
plotted using the bone age rather than chronologic age, the projected height is within the range predicted for the family and often within
the normal range for the population (ie, adult height that is ≥63 inches [160 cm] for men and ≥59 inches [150 cm] for women). There is often
a family history of delayed growth and/or puberty (a parent who was a "late bloomer"). (See "Causes of short stature", section on
'Constitutional delay of growth and puberty'.)
Are there features suggesting pathologic growth failure? — The history, review of systems, and physical examination should include the
following elements to assess for a variety of pathologic causes of short stature ( table 1 and algorithm 1). The findings may influence
selection of laboratory tests and/or imaging.
Features suggesting underlying systemic disease — A variety of systemic diseases is associated with attenuated growth during childhood,
usually with delayed bone age. This is particularly true for inflammatory disease processes (such as Crohn disease or juvenile idiopathic arthritis),
diseases that cause malabsorption or malnutrition, or those that increase energy needs (cardiac or immune defects). Therefore, a complete
medical history and review of systems are important to the assessment of short stature.
Key elements of the history include (see "Causes of short stature", section on 'Systemic disorders with secondary effects on growth'):
● Gastrointestinal symptoms, including appetite, abdominal pain, diarrhea, and rectal bleeding – Suggests the possibility of Crohn disease or
celiac disease.
● Pulmonary symptoms, including severe asthma, recurrent infections – Suggests the possibility of cystic fibrosis or immunodeficiency.
● Recurrent infections – Suggests the possibility of immunodeficiency; recurrent otitis media with the need for myringotomy tubes is
associated with Turner syndrome.
● Arthralgia or arthritis – Consistent with inflammatory bowel disease, rheumatic diseases (eg, juvenile idiopathic arthritis), or celiac disease.
● Medications – Prolonged or frequent use of glucocorticoids (including inhaled glucocorticoids) may contribute to growth failure (see "Causes
of short stature", section on 'Glucocorticoid therapy'). Use of stimulants for attention deficit hyperactivity disorder also has been associated
with mild delay in growth, although this effect usually is transient. (See "Causes of short stature", section on 'Systemic disorders with
secondary effects on growth' and "Pharmacology of drugs used to treat attention deficit hyperactivity disorder in children and adolescents",
section on 'General adverse effects'.)
Key elements of the physical examination include:
● Weight loss, poor weight gain, underweight for height, and/or delayed puberty – These findings are consistent with many underlying
systemic diseases, psychosocial deprivation, or food restriction. By contrast, most endocrine causes of short stature are associated with
overweight for height.
● Oral ulcers or large anal skin tags – These findings are common in Crohn disease and may be the presenting symptoms.
Features suggesting genetic or endocrine disease — Endocrine disorders are relatively uncommon causes of short stature but important to
diagnose because they respond to specific treatment(s). These endocrine disorders are often characterized by delayed bone age. An exception is
precocious puberty, in which accelerated early growth may be accompanied by early epiphyseal maturation and adult short stature.
Key elements of the history relevant to endocrine disease include (see "Causes of short stature", section on 'Endocrine causes of growth failure'):
● Sluggishness, lethargy, cold intolerance, constipation – These symptoms suggest hypothyroidism.
● Developmental delay/learning disabilities – Problems with nonverbal learning skills are common in Turner syndrome. Developmental delay is
common in Noonan or Russell-Silver syndrome and in pseudohypoparathyroidism. Acquired hypothyroidism is often associated with altered
school performance. Many syndromes with developmental delay also include short stature, such as Down, Prader-Willi, and Bloom
syndromes.
● Neuropsychological changes – Symptoms of psychiatric disease occur in over one-half of patients with Cushing syndrome of any etiology.
Key elements of the physical examination include:
● Increased weight for height – Obesity is nearly universal in Cushing syndrome (with central fat distribution). Increased weight for height is
also consistent with hypothyroidism, growth hormone deficiency, or pseudohypoparathyroidism.
● Facial dysmorphism
• Hypertelorism, downward eye slant, low-set ears – Noonan syndrome.
• Prominent forehead, triangular face, downturned corners of the mouth – Russell-Silver syndrome.
• Midface hypoplasia, frontal bossing – Achondroplasia.
• Midline defects – Associated with hypothalamic-pituitary hormone deficiencies.
● Optic discs – Papilledema suggests a central nervous system mass effect. Optic nerve hypoplasia suggests septo-optic dysplasia, which is
associated with pituitary hormone deficiencies. In optic nerve hypoplasia, the optic disc is small, often pale, and surrounded by a yellowish
halo, bordered by a ring of pigmentation (double-ring sign) ( picture 1).
● Neck and chest

• Goiter – Hypothyroidism.
• Webbed neck, shield chest ( picture 2) – Characteristic findings in Turner syndrome.
• Webbed neck, pectus excavatum – Seen in Noonan syndrome.
• Suprascapular fat pad (buffalo hump) and supraclavicular fat pads – Suggests Cushing syndrome. Mild forms of this fat distribution are
seen in simple obesity (sometimes termed "pseudo-Cushingoid"), but exogenously obese children are often of normal or slightly
increased stature.
● Limbs
• Cubitus valgus (increased carrying angle of the arm), genu valgum – Commonly seen in Turner syndrome or SHOX gene (short stature
homeobox) mutations.
• Madelung deformity of the forearm (focal dysplasia of the distal radial physis, leading to a prominent ulna and wrist pain) ( picture 3
and image 1) – Commonly seen in Turner syndrome or SHOX mutations.
• Stocky build – Often seen in Turner syndrome or SHOX mutations.
• Long limbs compared with trunk – Spondyloepiphyseal dysplasia.
• Short limbs (especially upper arms) compared with trunk – Achondroplasia.

• Trident hands (broad, space between middle fingers) – Achondroplasia.
● Skin – Atrophied skin and purple-colored striae are characteristic of Cushing syndrome, sometimes with hyperpigmentation.
● Delayed or accelerated puberty or hypogonadism – Most women with Turner syndrome have absent breast development; some have
delayed puberty. Hypothyroidism tends to cause pubertal delay, although, on rare occasion, this disorder may present with precocious
puberty. Early puberty is occasionally found in children with congenital virilizing adrenal hyperplasia or Cushing disease. Microphallus or
cryptorchidism suggest central hypothalamic-pituitary deficiencies.
● Decreased deep tendon reflexes – Suggests hypothyroidism.
LABORATORY AND IMAGING STUDIES
There is some controversy about the extent of testing that should be performed for children and adolescents with presumed idiopathic short
stature. In otherwise healthy children, the yield of testing is extremely low. One study described the clinical evaluation of 235 children who were
referred for short stature and had height <3rd percentile but normal growth rate and no symptoms [27]. In this group of low-risk short children,
nearly 99 percent were ultimately diagnosed with variants of normal growth (23 percent with familial short stature, 41 percent with constitutional
delay of growth, and 36 percent with idiopathic short stature). The cost per new diagnosis identified was more than $100,000, although most
patients did not undergo all of the screening tests that have been recommended in consensus guidelines [11]. Because of the low diagnostic
yield and high cost, we suggest performing laboratory testing only selectively in otherwise asymptomatic children, as outlined below.
● A basic evaluation consisting of a bone age determination is appropriate for children with short stature, normal growth rate (eg, height
velocity [HV] at least 5 cm/year between four and six years of age and at least 4 cm/year between six years and puberty), and no other
symptoms. The bone age determination provides a more accurate assessment of adult height and clarifies the type of growth defect, as
described above (see 'Is there evidence of delayed or accelerated growth?' above). Screening for celiac disease is also reasonable for children
with gastrointestinal symptoms or first-degree relatives with celiac disease.
● Broader testing may be warranted if the child is severely short (eg, height ≤-2.5 standard deviations [SD], ie, 0.6th percentile), has growth
failure (eg, height-for-age curve crossing two major percentile lines, or HV <5 cm/year between four and six years of age and <4 cm/year
between six years and puberty), or if the history or physical examination raised suspicion for a specific systemic, endocrine, or genetic
disorder. Decisions regarding the extent of testing should be made in conjunction with a pediatric subspecialist but vary with the child's
presenting symptoms and the clinical setting. We perform the following battery of tests to screen for several pathologic causes of short
stature ( table 1), as outlined in a consensus statement [11]:
• Complete blood count (CBC) and erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP).
• Electrolytes, creatinine, bicarbonate, calcium, phosphate, alkaline phosphatase, albumin.
• Celiac serologies (eg, tissue transglutaminase [tTG] immunoglobulin A [IgA] and total IgA) – Several guidelines recommend celiac
screening for short stature, as well as for other indications. This test is relatively cost-effective and screens for a common disease. Some
celiac disease test panels include a measurement of total IgA to exclude the unlikely possibility of a false-negative test in a patient with
selective IgA deficiency. (See "Diagnosis of celiac disease in children", section on 'Whom to test'.)
• Thyroid-stimulating hormone (TSH), free thyroxine (T4), insulin-like growth factor 1 (IGF-1), and insulin-like growth factor binding protein-
3 (IGFBP-3). IGFBP-3 has higher sensitivity for predicting the diagnosis of growth hormone deficiency in children <10 years of age as
compared with IGF-1.
• Karyotype or comparative genomic hybridization should be performed in all girls to rule out Turner syndrome and in boys with
associated genital abnormalities.
● Additional testing for monogenic causes of short stature (eg, chromosomal microarrays targeted to specific collections of candidate
genes) may be useful in selected patients [28,29]. Candidates for this more intensive genetic testing may include children with [30]:
• Severe growth hormone deficiency

• Severe short stature (height below -3 SD)
• Multiple pituitary hormone deficiency
• Unequivocal growth hormone insensitivity
• Children born small for gestational age who do not experience catch-up growth
• Additional congenital anomalies or dysmorphic features
• Evidence of a skeletal dysplasia

• Associated intellectual disability or microcephaly
(See "Tools for genetics and genomics: Cytogenetics and molecular genetics", section on 'Detecting known mutations'.)
● Morning luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in children with signs of sexual precocity ("ultrasensitive" assays
should be used for pediatric patients, and samples should be drawn in the early morning for optimal sensitivity). (See "Definition, etiology,
and evaluation of precocious puberty".)
Additional testing for specific disorders is appropriate if the history and physical examination suggest a particular diagnosis, such as precocious
puberty or an endocrine, skeletal, or syndromic cause of growth failure, as described above. (See 'Are there features suggesting pathologic
growth failure?' above and "Causes of short stature", section on 'Pathologic causes of growth failure' and "Skeletal dysplasias: Approach to
evaluation".)
Patients with reduced HV, low IGF-1 and/or IGFBP-3, and delayed bone age should be evaluated for growth hormone deficiency using provocative
tests. (See "Diagnosis of growth hormone deficiency in children".)
Contrast-enhanced magnetic resonance imaging of the brain is appropriate for children with established growth hormone deficiency or in those
with signs or symptoms suggesting hypothalamic-pituitary dysfunction (eg, hypoglycemia, microphallus, cryptorchidism, septo-optic dysplasia,
intracranial tumor, or history of cranial irradiation).
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See
"Society guideline links: Turner syndrome" and "Society guideline links: Growth hormone deficiency and other growth disorders".)
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written
in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics
patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and
are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can
also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
● Basics topic (see "Patient education: My child is short (The Basics)")
SUMMARY AND RECOMMENDATIONS
● Short stature is defined as height that is 2 standard deviations (SD) or more below the mean height for children of that sex and chronologic
age in a given population. This translates to a height that is below the 2.3rd percentile. The clinical significance of the short stature depends
on many factors, including genetic potential and changes in stature over time (height velocity [HV]). (See 'Is the child short?' above.)
● Determination of the child's growth, or HV, is an essential component of the evaluation for short stature. For children two years and older,
growth failure is suggested by a growth pattern that has deviated downward across two major height percentile curves or by growth slower
than the following rates:
• Age two to four years – HV less than 5.5 cm/year (<2.2 inches/year)
• Age four to six years – HV less than 5 cm/year (<2 inches/year)
- HV less than 4 cm/year for boys (<1.6 inches/year)
- HV less than 4.5 cm/year for girls (<1.8 inches/year)
(See 'Is the child's height velocity impaired?' above.)
● An estimate of a child's adult height potential can be obtained by calculation of the midparental height (target height), adjusted for the sex of
the child (calculator 4). For boys and girls, 8.5 cm (3.3 inches) on either side of this calculated value represents the 3rd to 97th percentiles for
anticipated adult height. (See 'Is the child's growth within the range for the family?' above.)
● The history and physical examination should include (see 'Additional evaluation for causes of short stature' above):
• Family history of growth and pubertal onset

• Review of systems for features suggestive of gastrointestinal, pulmonary, immunologic, or other systemic disease
• Dysmorphic features, especially webbed neck, cubitus valgus, and absent puberty in girls (suggests Turner syndrome), or
disproportionate short stature (ie, short limbs compared with trunk)
● The two most common causes of short stature are familial (genetic) short stature and constitutional delay of growth and puberty (CDGP),
which are variants of normal growth. These growth patterns often can be distinguished from one another, but some children have features
of both ( table 2). (See 'Are there features that suggest that this is a normal variant of short stature?' above.)
● Important pathologic causes of growth failure that may present with short stature and/or delayed puberty include Crohn disease, celiac
disease, and Turner syndrome ( table 1). (See 'Are there features suggesting pathologic growth failure?' above.)
● Laboratory evaluation for a child with short stature depends on the results of the above evaluation ( algorithm 1).
• For children with short stature, normal growth rate (eg, HV at least 5 cm/year between four and six years of age and at least 4 cm/year
between six years and puberty), and no other symptoms, we suggest a basic evaluation including bone age determination. The bone
age result can then be used to refine the estimate for the child's adult height and also informs the evaluation for possible causes of
short stature. (See 'Bone age determination' above and 'Laboratory and imaging studies' above.)
• Children with severe short stature (eg, height ≤-2.5 SD [0.6th percentile]) or growth failure should be further evaluated with a complete
blood count (CBC), erythrocyte sedimentation rate (ESR), tissue transglutaminase (tTG) immunoglobulin A (IgA), creatinine, electrolytes,
thyroid-stimulating hormone (TSH), free thyroxine (T4), insulin-like growth factor 1 (IGF-1), and insulin-like growth factor binding protein-
3 (IGFBP-3). A karyotype or comparative genomic hybridization should be performed in all girls with unexplained short stature (to
evaluate for Turner syndrome) and in short boys with associated genital abnormalities. Abnormal results of these tests and/or
symptoms are signs that a disorder causing growth failure warrants further investigation. (See 'Laboratory and imaging studies' above
and "Causes of short stature", section on 'Endocrine causes of growth failure'.)
Use of UpToDate is subject to the Subscription and License Agreement.
REFERENCES
1. Grimberg A, Kutikov JK, Cucchiara AJ. Sex differences in patients referred for evaluation of poor growth. J Pediatr 2005; 146:212.
2. August, GP, Lippe, BM, Blethen, SL. et al. Growth hormone treatment in the United States demographic and diagnostic features of 2331 child
ren. In: National cooperative growth study (NCGS) advisory group, Growth Hormone: Science, Research, and the NCGS: 10 years of research,
Gardiner-Caldwell SynerMedCalifon, NJ, 1996. p. 179.
3. Chatelain P. Trends in the diagnosis and treatment of short stature as revealed by KIGS. In: Growth Hormone Therapy in KIGS: 10 Years' Expe
rience, Ranke, MB, Wilton, P (Eds), Johann Ambrosius Barth Verlag, Heidelberg, 1999. p. 11.
4. Grimberg A, Feemster KA, Pati S, et al. Medically underserved girls receive less evaluation for short stature. Pediatrics 2011; 127:696.
5. Grimberg A, Huerta-Saenz L, Grundmeier R, et al. Gender Bias in U.S. Pediatric Growth Hormone Treatment. Sci Rep 2015; 5:11099.
6. Karlberg J. A biologically-oriented mathematical model (ICP) for human growth. Acta Paediatr Scand Suppl 1989; 350:70.
7. HEALY MJ, LOCKHART RD, MACKENZIE JD, et al. Aberdeen growth study. I. The prediction of adult body measurements from measurements
taken each year from birth to 5 years. Arch Dis Child 1956; 31:372.
8. Kerrigan JR, Rogol AD. The impact of gonadal steroid hormone action on growth hormone secretion during childhood and adolescence.
Endocr Rev 1992; 13:281.
9. Tanner JM, Davies PS. Clinical longitudinal standards for height and height velocity for North American children. J Pediatr 1985; 107:317.
10. Miller BS, Sarafoglou K, Addo OY. Development of Tanner Stage-Age Adjusted CDC Height Curves for Research and Clinical Applications. J
Endocr Soc 2020; 4:bvaa098.
11. Cohen P, Rogol AD, Deal CL, et al. Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary
of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric
Endocrinology Workshop. J Clin Endocrinol Metab 2008; 93:4210.
12. Alexandrou E, Cabrera-Salcedo C, Labilloy G, et al. Algorithm-Driven Electronic Health Record Notification Enhances the Detection of Turner
Syndrome. J Pediatr 2020; 216:227.
13. Tanner JM, Goldstein H, Whitehouse RH. Standards for children's height at ages 2-9 years allowing for heights of parents. Arch Dis Child
1970; 45:755.
14. Dauber A. Genetic Testing for the Child With Short Stature-Has the Time Come To Change Our Diagnostic Paradigm? J Clin Endocrinol Metab
2019; 104:2766.
15. Freire BL, Homma TK, Funari MFA, et al. Multigene Sequencing Analysis of Children Born Small for Gestational Age With Isolated Short
Stature. J Clin Endocrinol Metab 2019; 104:2023.
16. Greulich WW, Pyle SI. Radiographic atlas of skeletal development of the hand and wrist, Stanford University Press, Stanford 1976.
17. Tanner JM, Healy MJR, Goldstein H, Cameron N.. Assessment of Skeletal Maturity and Prediction of Adult Height (TW3 Method), 3rd Ed, WB Sa
unders, London 2001.
18. Pinchi V, De Luca F, Ricciardi F, et al. Skeletal age estimation for forensic purposes: A comparison of GP, TW2 and TW3 methods on an Italian
sample. Forensic Sci Int 2014; 238:83.
19. Creo AL, Schwenk WF 2nd. Bone Age: A Handy Tool for Pediatric Providers. Pediatrics 2017; 140.
20. Malina RM. Skeletal age and age verification in youth sport. Sports Med 2011; 41:925.
21. BAYLEY N, PINNEAU SR. Tables for predicting adult height from skeletal age: revised for use with the Greulich-Pyle hand standards. J Pediatr
1952; 40:423.
22. Bertaina C, Stasiowska B, Benso A, Vannelli S. Is TW3 height prediction more accurate than TW2? Preliminary data. Horm Res 2007; 67:220.
23. Gilli G, Hoppe W, Benso L. TW3 method for prediction of adult height in children with congenital renal diseases. Medimond: Proceedings of t
he 12th International Congress of Endocrinology, Lisbon, 2004; p. 1419-23.
24. Roemmich JN, Blizzard RM, Peddada SD, et al. Longitudinal assessment of hormonal and physical alterations during normal puberty in boys.
IV: Predictions of adult height by the Bayley-Pinneau, Roche-Wainer-Thissen, and Tanner-Whitehouse methods compared. Am J Hum Biol
1997; 9:371.
25. Topor LS, Feldman HA, Bauchner H, Cohen LE. Variation in methods of predicting adult height for children with idiopathic short stature.
Pediatrics 2010; 126:938.
26. Gkourogianni A, Andrew M, Tyzinski L, et al. Clinical Characterization of Patients With Autosomal Dominant Short Stature due to Aggrecan
Mutations. J Clin Endocrinol Metab 2017; 102:460.
27. Sisley S, Trujillo MV, Khoury J, Backeljauw P. Low incidence of pathology detection and high cost of screening in the evaluation of
asymptomatic short children. J Pediatr 2013; 163:1045.
28. Argente J, Tatton-Brown K, Lehwalder D, Pfäffle R. Genetics of Growth Disorders-Which Patients Require Genetic Testing? Front Endocrinol
(Lausanne) 2019; 10:602.
29. Mintz CS, Seaver LH, Irons M, et al. Focused Revision: ACMG practice resource: Genetic evaluation of short stature. Genet Med 2021; 23:813.
30. Dauber A, Rosenfeld RG, Hirschhorn JN. Genetic evaluation of short stature. J Clin Endocrinol Metab 2014; 99:3080.
Topic 5834 Version 37.0
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GRAPHICS
Estimates for normal growth rates in children
Normal length or height at various ages during childhood, and the growth rate between those timepoints, are approximated
by multiples of five when measured in centimeters (this is sometimes termed the "rule of fives"). Actual height and growth
rate in a healthy child can vary substantially around these approximations.
* Growth rates may be considerably higher in the later end of this age range for children who have entered their pubertal growth spurt.
In girls, the pubertal growth spurt typically starts around age 10 but may start as early as age 8 in early maturing girls. In boys, the
pubertal growth spurt typically starts around age 12 but may start as early as age 10 in early maturing boys.
Graphic 70382 Version 8.0
Algorithm for the evaluation of a child with short stature*
This algorithm describes the detailed evaluation of a child with short stature. Some components of the evaluation can reasonably be performed in the primary care setting, including initial
interpretation and height velocity, and initial laboratory screening for an underlying systemic disease, if suspected based on symptoms. Other components of the evaluation, including bone age
interpretation and the detailed evaluation for causes of short stature, are typically performed by a pediatric endocrinologist, if available.
GDPP: gonadotropin-dependent precocious puberty (central sexual precocity); GIPP: gonadotropin-independent precocious puberty (peripheral sexual precocity); ISS: idiopathic short stature; CDGP:
constitutional delay of growth and puberty; SD: standard deviation; GH: growth hormone.
* Short stature is defined as height that is 2 SD or more below the mean (Z-score ≤–2) for children of the same sex and chronologic age in a given population. This corresponds to a height that is below the 2.3 rd
percentile.
¶ Decreased height velocity is indicated by a growth rate <5.5 cm/year from 2 to 4 years of age, <5 cm/year from 4 to 6 years of age, <4 cm/year from age 6 years to puberty, or crossing 2 major percentile lines
on a standard height-by-age chart.
Δ Systemic diseases may present with signs and symptoms either before or after they affect height or height velocity. This is especially true for inflammatory diseases (Crohn disease, juvenile idiopathic arthritis)
or any disorder that affects nutrition.
◊ Bone age determination requires expert interpretation of the hand radiograph using the Greulich and Pyle Atlas. If bone age is delayed or advanced, the height velocity percentile and projected height should
be recalculated based on bone age.
§ Delayed or advanced bone age is defined as a bone age that is 2 SD or more below or above the mean, respectively. This translates to difference between bone age and chronologic age of approximately 12
months between 2 and 4 years of chronologic age, 18 months between 4 and 12 years, and 24 months after age 12.
¥ Evaluation for systemic, endocrine, or genetic disorders includes a focused history and physical examination (refer to topic review on evaluation for short stature). In addition, patients with growth failure
usually should have laboratory screening, including a complete blood count, erythrocyte sedimentation rate or C-reactive protein, tissue transglutaminase, creatinine, electrolytes, bicarbonate, calcium,
phosphate, alkaline phosphatase, albumin, thyroid-stimulating hormone, free thyroxine (T4) and insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3). A karyotype should
be performed in all girls with unexplained short stature and in short boys with associated genital abnormalities [1]. Some or all of this evaluation is typically performed by a pediatric subspecialist but varies with
the child's presenting symptoms and the clinical setting.
‡ CDGP is particularly likely if there is a family history of this growth pattern (eg, relatively late puberty).
Reference:
1. Cohen P, Rogol AD, Deal CL, et al. Consensus statement on the diagnosis and treatment of children with idiopathic short stature: A summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric
Endocrine Society, and the European Society for Paediatric Endocrinology Workshop. J Clin Endocrinol Metab 2008; 93:4210.
Height measurement technique
The child's shoes and any hats or hair ornaments are removed. The child faces
away from the wall with the heels together and the back as straight as possible.
The head, shoulders, buttocks, and heels should be in contact with the vertical
surface. With the child looking straight ahead, the head projection is placed at the
crown of the head. The child steps away from the wall, and the height
measurement is recorded to the nearest 0.1 cm.
Length-for-age percentiles, males 0 to 24 months, WHO growth standards
WHO: World Health Organization.
Reproduced from: Centers for Disease Control and Prevention based on data from the WHO Child Growth Standards.
Length-for-age percentiles, females 0 to 24 months, WHO growth standards
WHO: World Health Organization.
Reproduced from: Centers for Disease Control and Prevention based on data from the WHO Child Growth Standards.
Stature-for-age percentiles, males 2 to 20 years, CDC growth charts: United States
CDC: Centers for Disease Control and Prevention.
From National Health Center for Health Statistics in collaboration with the National Center for Chronic Disease
Prevention and Health Promotion (2000).
Stature-for-age percentiles, females 2 to 20 years, CDC growth charts: United

States
From National Health Center for Health Statistics in collaboration with the National Center for Chronic Disease
Prevention and Health Promotion (2000).
Height velocity in American boys
Height velocity by age for American boys. The main set of curves (black lines) is centered on the
population with average timing of peak growth velocity (around 13.5 years for boys) and show an
approximate trajectory for individual children with this average pubertal timing. The 2 other
curves outline a trajectory (50 th percentile) for a child with "early" (solid blue) or "late" (solid
orange) timing of peak growth velocity.
Other height velocity curves have been developed that reflect population averages (eg, Kelly A,
JCEM 2014, not shown here). Those curves are substantially flatter than the trajectory followed by
any individual patient. they are based on data from a more recent and ethnically diverse
population of children and are valuable for understanding overall growth patterns in the
population but are less appropriate for evaluation of the growth of an individual patient.
SD: standard deviations.
Reproduced with permission from: Tanner JM, Davies S. Clinical longitudinal standards for height and height
velocity for North American children. J Pediatr 1985; 107:317. Copyright © 1985 Elsevier.
Height velocity in American girls
Height velocity by age for American girls. The main set of curves (black lines) is centered on the
population with average timing of peak growth velocity (around 11.5 years for girls) and show an
approximate trajectory for individual children with this average pubertal timing. The 2 other
curves outline a trajectory (50 th percentile) for a child with "early" (solid blue) or "late" (solid
orange) timing of peak growth velocity.
Other height velocity curves have been developed that reflect population averages (eg, Kelly A,
JCEM 2014, not shown here). Those curves are substantially flatter than the trajectory followed by
any individual patient. they are based on data from a more recent and ethnically diverse
population of children and are valuable for understanding overall growth patterns in the
population but are less appropriate for evaluation of the growth of an individual patient.
SD: standard deviations.
Reproduced with permission from: Tanner JM, Davies S. Clinical longitudinal standards for height and height
velocity for North American children. J Pediatr 1985; 107:317. Copyright © 1985 Elsevier.
Estimated projected height using current growth channel
Projected height provides a crude estimate of adult height in healthy children. Projected height is
determined by extrapolating the child's growth along the current channel to the 18- to 20-year
mark. In the example above, the 6-year-old boy is 43.5 inches (point A), which is at the 10 th
percentile. His projected adult height is the 10 th percentile height for a 20-year-old (point B): 66
inches.
Projected height is only weakly correlated with actual adult height, especially for young children,
and has minimal predictive value for children younger than 2 years. Projected height does not
provide a valid estimate of adult height in children with delayed or advanced bone age or a variety
of pathologic causes of short stature.
From: National Health Center for Health Statistics in collaboration with the National Center for Chronic Disease
Prevention and Health Promotion.
Chronological age versus bone age for boys
This chart depicts bone age as compared with chronological age in boys. The normal range is represented by 2 standard
deviations (SD) above and below the mean (white area on this chart). Bone age is delayed if it is below this threshold
(blue area), and advanced if it is above this threshold (green area). In clinical practice, a bone age that is 20 percent
below or above the chronological age is considered abnormal. These data are based on the Brush Foundation Study,
performed in well-nourished White children in the 1930s and 1940s.
Reference:
1. Greulich WW, Pyle SI. Radiographic Atlas of Skeletal Development of the Hand and Wrist, 2nd Edition, Stanford, CA: Stanford
University Press and London, UK: Oxford University Press, 1959.
Data from: Gaskin CM, Kahn SL, Bertozzi JC, Bunch PM. Skeletal development of the hand and wrist. Oxford University Press, New York
2011. p.8.
Chronological age versus bone age for girls
This chart depicts bone age as compared with chronological age in girls. The normal range is represented by 2 standard
deviations (SD) above and below the mean (white area on this chart). Bone age is delayed if it is below this threshold
(blue area), and advanced if it is above this threshold (green area). In clinical practice, a bone age that is 20 percent below
or above the chronological age is considered abnormal. These data are based on the Brush Foundation Study, performed
in well-nourished White children in the 1930s and 1940s.
Reference:
1. Greulich WW, Pyle SI. Radiographic Atlas of Skeletal Development of the Hand and Wrist, 2nd Edition, Stanford, CA: Stanford
University Press and London, UK: Oxford University Press 1959.
Data from: Gaskin CM, Kahn SL, Bertozzi JC, Bunch PM. Skeletal development of the hand and wrist. Oxford University Press, New York 2011.
p.8.
Major causes of short stature
Distinguishing features Typical evaluation Treatment Bone age Height velocity
Normal variants of growth
Familial short stature* Short parent(s), often below Hx, PE, bone age. None needed. Reassurance; Normal Low-normal
the 10 th percentile. Adult monitor growth. Eg, from age 6 until puberty:
height short for population,
Girls about 4 to 5
but within the range predicted
cm/year
by parents' height.
Boys about 3.5 to 4.5
cm/year
Constitutional delay of Normal height for bone age Hx, PE, bone age. None needed. Reassurance; Delayed Slow during first 3 to 5 years
growth and puberty* but not for chronological age. Be alert for the monitor growth; +/– treatment of life; normal during
Often family history of delayed possibility of underlying with sex steroids during childhood; pubertal growth
growth and/or puberty. Adult systemic disease puberty. spurt is delayed but
height usually normal. Laboratory screening if prolonged, often resulting in
height velocity is slow normal adult height
SGA infant, with catch-up Most SGA infants catch up by Hx, PE, bone age. Monitor growth to distinguish Normal Normal
growth two years of age; the For prematurely born from the 10% of SGA infants
remainder have slower or infants, adjust height for who do not have catch-up
absent catch-up growth that gestational age (up to 1 growth.
can be considered pathologic. year of chronological
age)
Pathologic causes of growth failure
Systemic disorders or processes with secondary effects on growth
Undernutrition Low weight-for-height. Hx (including dietary and Reverse nutritional deficit. Delayed or normal Slow (eg, <4 cm/year)
social Hx), PE, bone age.
Glucocorticoid therapy Growth effects are dose Hx, PE. Minimize glucocorticoid dose Delayed Slow
related, greatest with systemic Assess contribution of or give on alternate days if
dosing. Mild effects may occur underlying disease to feasible; consider alternate
with long-term use of inhaled growth deficit drugs.
glucocorticoids.
GI disease (especially GI symptoms (diarrhea, Hx, PE, bone age. Diagnose and treat underlying Delayed Slow
Crohn disease and celiac abdominal pain). Crohn Screening laboratory disease, improve nutrition,
disease) disease may have oral ulcers tests including CBC, ESR avoid glucocorticoids.
and anal fissures/skin tags. or CRP, celiac serologies
Rheumatologic disease Fever, arthralgias, rash, Hx, PE, bone age. Diagnose and treat underlying Delayed Slow
(especially systemic lymphadenopathy. Screening laboratory disease, improve nutrition,
onset juvenile idiopathic tests including CBC and avoid glucocorticoids.
arthritis) ESR or CRP, ANA, RF
Renal disease (CKD, Growth impairment may Hx, PE, bone age. Diagnose and treat underlying Delayed Slow
renal tubular acidosis) precede the diagnosis of CKD. Screening laboratory disease, maximize nutrition;
Other symptoms of CKD may tests including BUN, GH if needed.
include polyuria, edema, creatinine, and urine
elevated creatinine, tea- analysis
colored urine, and
hypertension.
Cancer Any cancer: Multiple Hx, PE, bone age. Ensure adequate nutrition; Delayed Slow
mechanisms for growth For children with history treat any secondary pituitary
failure, including decreased of cancer, or with CNS hormone deficiencies (eg, GH
intake, increased energy symptoms or deficiency).
needs hypothalamic-pituitary
Brain cancer: Direct effects disease: Screening
on hypothalamic-pituitary laboratory tests to
function assess pituitary function
Cancer treated with CNS (free T4, IGF-I, IGFBP-3),
radiotherapy or +/– head MRI with
chemotherapy: May have contrast
direct effects on GH
production, with late
effects on growth
Pulmonary disease (eg, Respiratory symptoms, Hx, PE, bone age. Test for CF Diagnose and treat underlying Delayed Slow
cystic fibrosis, immune recurrent infections: and immune deficiencies. disease, ensure adequate
deficiencies with In CF: steatorrhea/GI nutrition, avoid
recurrent pulmonary symptoms, failure to glucocorticoids.
infections, or severe thrive
asthma)
Immunologic disease Recurrent infections Hx, PE, bone age. Diagnose and treat underlying Delayed Slow
(manifestations vary Work-up for immune disease.
depending on type of deficiencies (refer to
immunodeficiency). topic review on children
with recurrent
infections)
Endocrine causes of growth failure
Hypothyroidism Sluggishness, lethargy, cold Hx, PE, bone age. Thyroid hormone Delayed Slow
intolerance, constipation, TSH and free T4. If replacement.
decreased reflexes. hypothyroidism is
central (low TSH and low
T4), also assess for other
pituitary hormone
deficiencies.
Cushing syndrome Obesity with central fat Hx, PE, bone age. Diagnose and treat underlying Delayed Slow
distribution; buffalo hump; 24-hour urine collection disease.
purple striae. for free cortisol
GH deficiency Progressive growth failure. Hx, PE, bone age. rGH. Delayed Slow
May also have symptoms of Measurements of GH,
other pituitary hormone IGF-I, and IGFBP-3 ¶
deficiencies.
Precocious puberty Virilization. Hx, PE, bone age. Treatment depends on type of Advanced Initially fast, then stops early
LH, FSH ¶ precocious puberty.
Genetic diseases with primary effects on growth
Turner syndrome Square "shield" chest, webbed Karyotype analysis (for 45,X, Estrogen, GH. Normal Slow
neck, cubitus valgus Δ, genu structural abnormality of X, or
valgum, Madelung mosaic).
deformity ◊.
Up to 50% have only short
stature and absent pubertal
development.
SHOX mutations May have isolated short Molecular genetic testing for Consider GH. Normal Slow
stature (usually stocky SHOX abnormalities.
appearance) or additional
features: Shorter forearms
and lower legs, cubitus
valgus Δ, Madelung
deformity ◊, high arched
palate.
Noonan syndrome Minor facial dysmorphism, Molecular genetic testing for Consider GH. Normal Low-normal or slow
heart disease, intellectual PTPN11, SOS1, and other
disability, webbed neck, pectus genes. ¶
excavatum, cryptorchidism.
Silver-Russell syndrome Severe intrauterine growth Clinical diagnosis, supported Consider GH. Normal Slow
restriction and postnatal by molecular genetic testing. ¶
growth retardation. Prominent
forehead, triangular face,
downturned corners of the
mouth, and body asymmetry
(hemihypertrophy).
Skeletal dysplasias
Achondroplasia Short arms and legs, midface Clinical diagnosis. Management of Mildly delayed Slow
hypoplasia, trident hands. Genetic testing for FGFR3 complications, which may
Most cases identified mutations is available ¶ include craniocervical junction
prenatally or in early infancy. compression, sleep apnea,
spinal stenosis.
Hypochondroplasia Short arms and legs similar to Skeletal survey. Surveillance for spinal ? Normal Slow
but milder than in Genetic testing for FGFR3 stenosis, with surgery as
achondroplasia; lumbar mutations (positive in needed.
lordosis. May include 70%)
macrocephaly, epilepsy.
Spondyloepiphyseal Heterogeneous Anthropometrics; skeletal Surveillance for spinal ? Normal Slow

dysplasia manifestations; trunk survey. disorders and osteoarthritis,
disproportionately shortened with surgery as needed.
compared with limbs; may
develop scoliosis, kyphosis,
and osteoarthritis.
Osteogenesis Children with moderate to Skeletal survey. Bisphosphonates, fracture Normal Low-normal or slow
imperfecta severe disease are usually management.
recognized by recurrent
fractures but also develop
short stature. Blue sclerae,
scoliosis, and hearing loss may
be present.
Hx: history; PE: physical examination; SGA: small for gestational age; GI: gastrointestinal; CBC: complete blood count; ESR: erythrocyte sedimentation rate; CRP: c-reactive protein; ANA: anti-nuclear
antibodies; RD: rheumatoid factor; CKD: chronic kidney disease; BUN: blood urea nitrogen; GH: growth hormone; CNS: central nervous system; T4: thyroid hormone; IGF-I: insulin-like growth factor I; IGFBP-
3: insulin-like growth factor binding protein 3; MRI: magnetic resonance imaging; CF: cystic fibrosis; TSH: thyroid-stimulating hormone; rGH: recombinant growth hormone; LH: luteinizing hormone; FSH:
follicle-stimulating hormone; SHOX: short stature homoeobox.
* Some patients have features of both familial short stature and constitutional delay of growth and puberty.
¶ Evaluation of patients in whom this disorder is suspected usually is performed by a subspecialist (ie, a pediatric endocrinologist, gastroenterologist, or geneticist).
Δ Cubitus valgus is an increased carrying angle of the arm.
◊ Madelung deformity is focal dysplasia of the distal radial physis, which can result in a prominent ulna and wrist pain.
Differential features of familial short stature and constitutional delay of growth and puberty
Feature Familial short stature Constitutional delay
Parents' stature Small (1 or both) Average
Parents' puberty Usual timing Often delayed
Birth length Normal or low-normal Normal
Growth (0 to 2 years) Normal Slow from mid-infancy to mid-childhood
Growth (2 years to puberty) Normal Slow
Bone age Normal Delayed
Timing of puberty Normal Delayed
Pubertal growth Rate low-normal Growth spurt delayed, rate slightly diminished
Adult height Short Normal
Optic nerve hypoplasia
At first glance, the disc may appear pale, but the actual disc substance is within this
pale area. Arrows indicate actual nerve borders.
Courtesy of Karl C Golnik, MD.
Clinical features of Turner syndrome
Eleven-year-old with classical appearance of 45,X Turner syndrome, including short

stature, lack of breast development, and shield chest with widely spaced nipples.
Additional features may include webbed neck, cubitus valgus, and shortened
fourth metatarsals.
Reproduced with permission from: Rebar RW, Paupoo AAV. Puberty. In: Berek and Novak's
Gynecology, Berek, JS (Ed), Philadelphia: Lippincott Williams & Wilkins, 2012. Copyright © 2012
Lippincott Williams & Wilkins. www.lww.com.
Madelung deformity of the forearm
(A, B) Clinical photographs of a patient with Madelung deformity. Note the seemingly prominent ulnar head
and apparent volar subluxation of the wrist on the forearm.
Reproduced with permission from: Waters PM, Bae DS. Pediatric Hand and Upper Limb Surgery. Lippincott Williams & Wilkins,
Philadelphia 2012. Copyright © 2012 Lippincott Williams & Wilkins. www.lww.com.
Madelung deformity radiographs
Radiographs of a Madelung deformity.

(A) Anteroposterior view.
(B) Lateral view.
Reproduced with permission from: Waters PM, Bae DS. Pediatric Hand and Upper Limb Surgery. Lippincott Williams & Wilkins,
Philadelphia 2012. Copyright © 2012 Lippincott Williams & Wilkins. www.lww.com.
Contributor Disclosures
Erick J Richmond, MD Speaker's Bureau: Pfizer [Growth hormone]; NovoNordisk [Growth hormone]; Merk [Growth hormone]; Sandoz [Growth hormone]. Alan D
Rogol, MD, PhD Consultant/Advisory Boards: Anteres and Clarus [Androgens]; Ascendis, Lumos Pharma, and Tolmar [Growth]; Ultragenyx [Rare diseases]; United
States Anti-Doping Agency [Anti-doping]. Mitchell E Geffner, MD Grant/Research/Clinical Trial Support: Novo Nordisk [Growth]. Consultant/Advisory Boards: Adrenas,
Eton, and Neurocrine Biosciences [CAH]; Daiichi-Sankyo [Type 2 diabetes]; Novo Nordisk, Pfizer, QED, and Ascendis [Growth]; Gilead [Growth/HIV]. Other Financial
Interest: McGraw-Hill [Pediatric endocrinology textbook royalties]. Alison G Hoppin, MD Nothing to disclose
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process,
and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to
UpToDate standards of evidence.
Conflict of interest policy

Diagnostic Approach To Children and Adolescents With Short Stature - UpToDate

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Diagnostic Approach To Children and Adolescents With Short Stature - UpToDate

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Diagnostic approach to children and adolescents with short stature - UpToDate 25/07/21 06.

Official reprint from UpToDate®

• Age two to four years – 5.5 to 9 cm/year (2.2 to 3.5 inches/year)

● How short is the child?

suspicion for pathologic causes of growth faltering is appropriate.

● Or, if the child is growing slower than the following rates:

ADDITIONAL EVALUATION FOR CAUSES OF SHORT STATURE

Key elements of the physical examination include:

● Sluggishness, lethargy, cold intolerance, constipation – These symptoms suggest hypothyroidism.

Key elements of the physical examination include:

● Neck and chest

• Short limbs (especially upper arms) compared with trunk – Achondroplasia.

● Decreased deep tendon reflexes – Suggests hypothyroidism.

LABORATORY AND IMAGING STUDIES

• Electrolytes, creatinine, bicarbonate, calcium, phosphate, alkaline phosphatase, albumin.

• Severe growth hormone deficiency

• Evidence of a skeletal dysplasia

SOCIETY GUIDELINE LINKS

INFORMATION FOR PATIENTS

● Basics topic (see "Patient education: My child is short (The Basics)")

SUMMARY AND RECOMMENDATIONS

(See 'Is the child's height velocity impaired?' above.)

• Family history of growth and pubertal onset

Use of UpToDate is subject to the Subscription and License Agreement.

Graphic 70382 Version 8.0

Algorithm for the evaluation of a child with short stature*

Graphic 94743 Version 6.0

Height measurement technique

Graphic 56127 Version 1.0

Length-for-age percentiles, males 0 to 24 months, WHO growth standards

WHO: World Health Organization.

Graphic 67950 Version 6.0

Length-for-age percentiles, females 0 to 24 months, WHO growth standards

WHO: World Health Organization.

Graphic 80511 Version 4.0

Stature-for-age percentiles, males 2 to 20 years, CDC growth charts: United States

CDC: Centers for Disease Control and Prevention.

Graphic 63399 Version 7.0

Stature-for-age percentiles, females 2 to 20 years, CDC growth charts: United

CDC: Centers for Disease Control and Prevention.

Graphic 77249 Version 6.0

Height velocity in American boys

SD: standard deviations.

Graphic 96367 Version 7.0

Height velocity in American girls

SD: standard deviations.

Graphic 96366 Version 6.0

Estimated projected height using current growth channel

CDC: Centers for Disease Control and Prevention.

Graphic 64811 Version 6.0

Chronological age versus bone age for boys

Graphic 94179 Version 5.0

Chronological age versus bone age for girls

Graphic 94180 Version 3.0

Major causes of short stature

Distinguishing features Typical evaluation Treatment Bone age Height velocity

Normal variants of growth

Pathologic causes of growth failure

Systemic disorders or processes with secondary effects on growth

Endocrine causes of growth failure

Genetic diseases with primary effects on growth

Spondyloepiphyseal Heterogeneous Anthropometrics; skeletal Surveillance for spinal ? Normal Slow