English Case Presentation I To Whom respectfully

Michael Mettafortuna S. Mr/Mrs……

Turner Syndrome
Introduction
Turner Syndrome (TS), is a disease cause by a complete or partial absence of one
X chromosome in a phenotypic female. Usually accompanied by short stature and
gonadal dysgenesis. It is characterized by edema of hand and feet, low birth weight,
webbed neck, low hair line, small mandible prominent auricula, epicanthic fold,
wide sized thorax, widely spaced nipple, high arched palate, short stature, cubitus
valgus, gonadal dysgenesis, primary amenorrhoea,
The classic form of TS is associated with a 45,X karyotype and occurs in
approximately one half of individuals with this condition.1,2 The main phenotypic
characteristic of patients with TS is a short stature, which is common to all patients.
Other manifestations will found are pelvic kidney, horse shoe kidney, ureteric
duplication, ureteropelvic narrowing, hydronephrosis with urinary abnormalities
most commonly associated with Turner syndrome.3 Karyotyping is considered to
be the gold-standard technique for diagnosing TS but has limitations because of
long processing time, high cost, and requirement for specialized personnel.4 TS
requires some therapies such as growth hormone and estrogen.5
Turner syndrome is likely to have various complications involving the
metabolic, autoimmune, cardiovascular, urinary system, bone and joint,
otolaryngological, central nervous systems, and psychosocial diseases in addition
to manifestations such as short stature and amenorrhea.6 TS causes a variety of
autoimmune diseases such as thyroiditis, colitis, celiac disease, type 1 diabetes, and
psoriasis, though the most common is autoimmune thyroiditis.7 On a global scale,
recent TS cases have been a trend toward obesity, in which the BMI, total fat mass,
and visceral fat levels are high and the muscle mass is low. BMI level and
prevalence of obesity in TS were significantly higher than those of general female
population in each age group between 15 and 39 years.7 The aim for this case
presentation is to point out the clinical manifestation, diagnosis approach, and
management of Turner Syndrome in children.

1
Case Report
AN 14 years old girl came to outpatient clinic pediatric department of Dr. M. Djamil
Hospital in December 30th 2019 referred from Arifin Achmad Hospital Pekanbaru.

Chief complaint: Feeling short than the other friends.

Present illness history:
Patient looks shorter than her friends with the same age and feel unsatisfied since
she was 12 years old and also feels unsatisfied of her school performance. She
hasn’t got menarche yet, there is no development of the breast. She has no complain
of headache, cough, breathlessness, palpitations, diarrhea, fever, seizure, bleeding,
urinary and bowel complains, and her appetite was good. She consult to Obstetry
and Gynecology department in The Arifin Achmad hospital to ask about her
menstruation in 2018 and the doctor said that she was normal and asked to wait for
few years. Still felt unsatisfied the patient consult to pediatric department of Arifin
Achmad hospital Pekanbaru in the end of 2018. She referred to endocrinology
pediatric department. In Arifin Achmad hospital, she did some examinations such
as bone age, hormonal examination, and chromosome analysis. In October 2019,
the result were given. The chromosome analysis showed 45,XO. In december 2019,
she was asked to go to Dr. M. Djamil Hospital pediatric department to be checked
in Endocrinology department of pediatric. She got therapy of Growth Hormone for
three months.

Family Illness History

There is no family history who suffered from same condition. There are no data of
infertility history in the family.

History of Delivery, Immunization and Development

Patient was the first child from three siblings, spontaneous delivery, aterm with
birth weight 2600 gram and birth length 46 cm, vigorous. Basic immunization was
complete. Growth and developmental history were normal. No data of complaints
in neonatal period.

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Family and Social Economy History
Her mother was 35 years old, graduated from nurse department. Her father was 33
years old, graduated from technical department, work as a private employee with
income approximately Rp 7.000.000/month. Patient and her family live in their own
home, a semipermanent house with good hygiene and sanitation.

Physical examination
She appeared moderately ill, alert, blood pressure 100/60 mmHg, heart rate 90 times
per minute, respiratory rate 22 times per minute, body temperature 36,8oC, body
weight 33 kg, body height 134 cm, weight for age was 89%, height for age was
100%, weight for height was 89%, Height age was 9 years 6 months. Skin was
warm, no cyanotic. Head was round and symmetric. Webbed neck. Low posterior
hair line. Conjuctival was not anemic, sclera was not icteric, pupil isochor with
diameter 2mm/2mm, light reflex was positive normal. Ears and nose were normal.
Tonsil was T1-T1, not hyperemic and pharynx was not hyperemic. Mouth’s mucous
was wet. Distance of inter papil mamillary. Ictus of heart wasn’t seen, ictus palpated
at left midclavicularis line, intercostal space V, on auscultation there is regular
rhythm, no murmur. On examination of thorax was normochest, no retraction, no
lagging breath, fremitus was the same in the right and left side, sonor percussion
in hemithorax dextra and sinistra, vesicular breathsound in hemithorax dextra and
sinistra, no rales, no wheezing. There were no abdominal distension, peristaltic
sound was normal. No pubic hair, small of labia majora, puberty state A1M1P1, looks
like infant. Extremities was warm with good perfusion, cubitis valgus,
physiological reflexes were positive normal, pathological reflexes were negative.
Skin was multiple nevi.

3
 Picture 1. Turner Syndrome Growth Chart
W/A : 33/37 = 89%
H/A : 134/134 = 100%
W/H : 33/37 = 89%

4
 Picture 2. Growth Chart
W/A : 33/49 = 67%
H/A : 134/160 = 83%
W/H : 33/28 = 117%

5
 Picture 3. Bone Age
The range of bone of girls within the age 11 years 9 months and 15 years 9 months.
Bone age appropriate for 10 years old girl.
Conclusion: Average girls

List of Problem
1. Short stature
2. Wide of papillary mammae distance
3. Low posterior hairline
4. Cubitus valgus
5. Webbed neck
6. Multiple nevi

Working Diagnosis
1. Turner’s syndrome
2. Short stature

Management
1. Turner’s syndrome
a. Diagnostic: anamnesis, physical examination, laboratory findings

6
 b. Treatment :
- Therapy
Saizen (Somatropin) 1x1.5 mg
- Planning : Lipid profile and blood glucose examination, follow up for
three months
c. Education: diagnosis, management, monitoring, complication, prognosis.

Laboratory Result:
Result Normal Value Interpretation
Hb 13,7 mg/dl 12-16 Normal
Ht 41,3% 37-47% Normal
WBC 5.810/mm3 4.800-10.800 Normal
Eritrocyte 5,49 million 3,7-6,5 million Normal
Platelet 324.000/mm3 150.000-450.000 Normal
MCV 75,2 79-99 Low
MCH 25 27-31 Low
MCHC 33,2 33-37 Normal

Endokrinology Result Normal Value Interpretation

FT4 1.13 ng/dL 0.81-1.66 ng/dL Normal
TSH 1.172 uIU/mL 0.70 – 4,61 Normal

Picture 4. Chromosome Analysis 45 XO

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Follow up on 7th of August 2020 (14 years 6 months old)
Growth velocity 2 cm / 6 months, menstruation negative, patient in growth hormone
therapy, school performance was normal, bowel and bladder normal. Height: 136
cm, weight: 36 kg, genitals A1M1P1, external genitalia was normal.
Assessment: Turner’s syndrome, short stature
Plan: Lipid profile and blood glucose examination, follow up regularly

Picture 5. Patient with her mother

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 Picture 6. Turner Syndrome Growth Chart Followed Up

W/A : 36/39 = 92%

H/A : 136/135 = 100,7%
W/H : 36/39 = 92%
9
 Picture 7. Growth Chart

W/A : 36/52 = 69%

H/A : 136/162 = 83%
W/H : 36/31 = 116%
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 LITERATURE REVIEW
Definition
Turner Syndrome (TS) is the consequence of complete or partial absence of one X
chromosome in a phenotypic female usually accompanied by short stature and
gonadal dysgenesis. The phrase “complete or partial” is used to include several
chromosomal etiologies leading to the syndrome. The most common is pure X
monosomy (45,X—formerly designated 45X0). Some authors do not believe that
complete X monosomy is compatible with survival and postulate the existence of a
normal cell line that rescues the embryo during early gestation. The classic form of
TS is associated with a 45,X karyotype and occurs in approximately one half of
individuals with this condition. Mosaic forms of TS (45,X/ 46,XX) account for one
fourth of Turner patients, whereas the rest have structural abnormalities of the X
chromosome.1,2,8
Characteristic of turner syndrome is low birth weight, webbing of neck, low
hair line, small mandible prominent auricula, epicanthic fold, wide sized thorax,
widely spaced nipple, high arched palate, short stature, cubitus valgus, gonadal
dysgenesis, primary amenorrhoea, and in neonatal phase can found edema dorsum
of hand and feet. Another abnormality most commonly associated with turner
syndrome is Pelvic kidney, horse shoe kidney, ureteric duplication, ureteropelvic
narrowing, hydronephrosis are urinary abnormalities.2

Epidemiology
The initial description of TS were short stature, sexual infantilism, cubitus valgus
and pterygium coli.3 Prevalence of 1 in 2000 to 2500 live born female children.5
According to study from 1999 to 2004, the incidence of TS in 119,158 births was
1/1,180 or 0.85%.9 The incidence rate of Chinese (0.90‰ or 1/1,111) is higher than
that of Malays (0.72‰ or 1/1,389) and India (0.38‰ or 1/2,632). In Indonesia itself,
TS is considered as rare disease with a very low number of cases. The incidence of
TS has increased according to a study in Denmark,8,10 and the known number of
surviving patients with TS steadily increased during that study.10 The diagnosis of
TS can occur at a wide range of ages. Turner syndrome is diagnoses in distinct age

11
groups, with peaks during fetal life, infancy, late pre pubescence (8-12 years) and
during late adolescence or early adulthood.11–15
TS is a disease that affects females. Prevalence of 1 in 2000 to 2500 live
born female children.5 The genetic background of the phenotype is highly variable,
and analysis of the karyotype can improve understanding of the disease. The
"classic" karyotype for TS is 45,X. Monosomy 45,X is present in about 45% of
cases, the remaining TS patients show a variety of chimeras and structural
abnormalities. the the remaining patients had a mosaic karyotype (i.e. 45,X/46,XX
or 45,X/47,XXX), a karyotype with an X chromosome structural abnormality (e.g.
i(Xq) or i(Xp)), or a karyotype that included the Y chromosome or fragments of the
Y chromosome.15,16
A karyotype analysis of 67 patients with TS in Suzhou, China identified the
45,X karyotype in 44.7%, a mosaic karyotype in 17.9%, a karyotype with a
chromosomal structural abnormality in 31.4%, and a karyotype that included the Y
chromosome or fragments of the Y chromosome in 6.0%.3 The 45,X karyotype was
the main karyotype in those areas.

Table 1. Karyotypes in patients with Turner syndrome in several Chinese Cities8

Genetics
Karyotype Monosomy Mosaic X chromosome structural Include the Y chromosome
(45,X) (45,X/46,XX,45,x/4 abnormality or fragments the Y
7,xxx) (isochromosome of long chromosome
arm, ring, or translocation)
Area total % total % total % Total %
Suzhou 30/6 44.7 12/67 17.9 21/67 31.4 4/67 6
7
Linyi 25/6 40.3 5/62 8.1 27/62 43.5 5/62 8.1
2
Zhenghou 8/18 44.4 5/18 27.8 5/18 27.8 / /
Fuzhou 13/5 22.4 10/58 17.3 30/58 51.7 5/58 8.6
8
Ningho 23/4 52.0 22/44 48 / / / /
4
Dalsan 32/7 41.0 16/78 20.5 30/78 38.5 / /
8
Beihai 20/7 27.4 22/73 30.1 18/73 24.7 13/73 17.8
3
Liuzhou 16/3 51.6 6/31 19.4 8/31 25.8 1/31 3.2
1

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 The variation of genotypic and phenotypic expression in gonadal dysgenesis
is caused by genetic errors in cell division in gonadal dysgenesis. Mosaic genotypes
typically have less severe phenotypic symptoms as compared to purer genotypes.
The characteristic features of TS result from either complete or partial functional
loss, particularly loss at the tip of the short arm or complete absence of the second
sex chromosome with the presence of one intact X chromosome. Functional loss or
absence of the second X chromosome can occur during either the meiotic or mitotic
phases of cell division. Absence of the second sex chromosome can be the result of
either the ovum or spermatozoon lacking the sex chromosome. Recent studies
report 70–80% of TS cases are caused by the loss of the parental sex chromosome.17

Picture 8. Chromosomal mosaicism.17

Picture 9. Monosomy Turner Syndrome.17

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 Picture 10. Partial deletion.17

Turner Syndrome with structural abnormalities of the X chromosome

isochromosome X [46,X,i(X)] has many forms such as, isochromosome is a
structural, ring Chromosome [46,X,r(X)] and deletion (Xp or Xq). Although classic
TS karyotype is 45,X, 30-40% of the remaining have a mosaic pattern with a second
cell line (45,X/46,XX, 45,X/47,XXX, 45,X/46,XY, 45,X/47,XYY and
46,X,delXq).6,18,19

Table 2. Type and frequency of chromosome abnormalities in Turner syndrome (TS)

(adapted from table 1)6

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Clinical Manifestasions
Clinicians need to be alert to the signs and symptoms associated with TS, especially
short stature, subnormal growth velocity, delayed puberty, primary amenorrhea, or
premature ovarian failure. Earlier diagnosis facilitates management, especially with
respect to growth hormone (GH) therapy.19
 Webbed neck
Excess skin folds around the neck cause it to seem broad (webbed neck) and/or
short.20,21 This anomaly is believed to result from subcutaneous nuchal oedema
during foetal life, leading to nuchal skin redundancy, which can persist
throughout life. Similar to other dysmorphic features, webbing of the neck may
be more or less prominent. Excess skin folds can be barely noticeable or of
considerable width extending from the mastoid process and laterally to the
acromion. Webbed neck was observed in over a half of our TS participants,
which is consistent with literature data.22 There was a sign of webbed neck in
patient.
 Childhood lymphoedema
Abnormal development of the lymphatic system may lead to lymphatic
insufficiency, and, consequently, to hand and feet swelling. Lymph fluid stasis
in the peripheral tissue typically produces chronic inflammation. Congenital
lymphoedema occurs in over 80% of TS-girls. Savendahl and Davenport used
lymphoedema as the key to diagnosis in 97% of the girls diagnosed with TS in
infancy, while short stature was the key to diagnosis for 82% of the girls
diagnosed in childhood or adolescence.11,23
 Finger/toe deformity
Typically, females with TS have disproportionately short legs and an abnormal
upper-to-lower segment ratio. Cervical vertebral hypoplasia contributes to short
stature. Scoliosis may be present in approximately 10% of TS females, and
approximately half have cubitus valgus or a wide carrying angle as a result of a
developmental defect of the ulnar head. Similar abnormalities of the medial tibial
and femoral condyles may also be present. Short metacarpals and metatarsals
can result in finger and/or toe deformities.24

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 Picture11. Patient with turner syndrome. A. At birth. Note the loose skin at the
posterior of the neck caused by the remains of cystic hygroma (fluid-filled cyst), the short
neck, malformed, and swelling in the hand B. And the foot C. Caused by lymphedema D.
At 6 years of age, the webbed neck is prominent and the nipples are widely spaced with a
broad chest.24

 Postural defects
Postural defects can be attributed, at least in part, to abnormalities in the growth
of long (limbs) and short (spine) bones. Short stature is the single most common
skeletal manifestation in patients with Turner syndrome. The incidence of short
stature in these patients ranges from 88% to 100%.24 The average height of adult
women with 45,X and non-45,X tends to differ significantly.25
All other skeletal anomalies common to Turner syndrome including short
metacarpals, cubitus valgus, high-arched palate, micrognathia, and short neck
have incidences of less than 60%. Cubitus valgus is an increase in the carrying
angle of the elbow and affects approximately 45% of patients with Turner
syndrome. This can also be accompanied by bowing and shortening of the
forearms. This is most commonly asymptomatic and requires no treatment other
than observation.24 There was a sign of cubitis valgus and short stature in patient.

16
 Spinal deformity, both in the frontal and sagittal planes, seems to occur more
frequently in patients with Turner syndrome compared with the general
population. Forty per cent of the Turner syndrome population examined by Elder
et al.21 had excessive kyphosis. The anterior vertebral wedging and irregular
vertebral epiphyseal growth rings result in a Scheuermann-like disease in Turner
syndrome. The incidence of thoracic hyperkyphosis has been reported to be
between 35% and 48%. The prevalence has been shown to increase with age,
suggesting a late-onset presentation (40% of hyperkyphosis presents after age 14
years).24
 Low posterior hairline
Individuals with Turner syndrome have a broad webbed neck and a low posterior
hairline. Co-occurrence of these features might indicate a common underlying
mechanism. Cabrol26 observed low posterior hairline in approximately half of
girls with TS, which is consistent with our results. However, the feature was
significantly more prevalent in women with 45,X monosomy. There was a sign
of low posterior hairline in patient.
 Pubertal induction and menarche induction
Gonadal dysgenesis is a type of hypogonadism found in Turner syndrome. Girls
with TS typically present with primary amenorrhoea. Only a small proportion
(approximately 10–16.5%) are likely to have spontaneous menarche; subsequent
menstrual cycles become irregular and tend to stop within 2–3 years. The mean
age at menarche is 14 years. In another study, 71% of TS women with pubertal
induction had menarche at the mean age of 17.2 years. Hagen et al. examined 66
patients with TS; the prevalence of spontaneous puberty was 6% for 45,X and
54% for other karyotypes.27 The genital of patient was A1M1G1 and looked like
infants.
 Neuropsychological deficits and social–emotional difficulties
Girls with TS have an increased likelihood of having executive functioning
deficits, attention deficit hyperactivity disorder (ADHD), and symptoms of
anxiety. They may also have more vulnerability socially, with increased rates of
difficulties in peer relationships. This psychological profile contributes to a
variable clinical presentation that ranges from girls who are markedly affected

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 to those with minimal or no challenges in these different domains. While each
construct (i.e., IQ, math skills, attention, anxiety) can be measured separately
and diagnoses such as specific learning disability in mathematics or ADHD can
be applied, when present in any combination they can interact with each other in
ways that can be complex such that they may compound each other and it can be
difficult to disentangle how each contributes to an individual's unique clinical
challenges.28

Picture12. Females with Tuner syndrome (TS) are at risk for different neuropsychological
deficits and social emotional difficulties that can interact with each other and that
contribute to the variability in the overall neuropsychological phenotype in girls with TS.

 Cardiovascular
Variations in the cardiovascular anatomy of patients with TS are major factors
in their reduced life expectancy. More advanced technology, has shown that the
number could be higher. It was found that approximately 70% had at least one
structural abnormality of the thoracic aorta or the proximal portions of the
branches of the aortic arch. Of these anomalies, elongation of the transverse
aortic arch (ETA) was the most common. It characterized by a left subclavian
artery (LSC) that originates posterior to the trachea, and a kink in the inferior
curvature leading to a more box-like-shaped arch. The bicuspid aortic valve is
the most common valvular abnormality associated with TS.29

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 Picture 13. illustration shows some of the common internal and external abnormalities
accompanying Turner syndrome 29

Diagnosis
The diagnosis of TS can occur at a wide range of ages.12,30,31 Prenatally, ultrasound
findings of increased nuchal translucency, cystic hygroma, left-sided obstructive
cardiac anomalies (especially coarctation of the aorta) in the fetus are highly
suggestive of TS.32 Maternal quadruple serum screening may also be abnormal, but
confirmatory testing with amniocentesis or chorionic villous sampling is necessary
to entertain the diagnosis of TS prenatally.5,30 It is, however, mandatory to repeat
the karyotype postnatally in all individuals who were previously diagnosed
prenatally.6,30 Noninvasive prenatal testing using maternal cell free DNA has not
been shown to have a good positive predictive value to diagnose TS and is therefore
not recommended for prenatal diagnosis of TS. 5,33
Turner syndrome is diagnoses in distinct age groups, with peaks during fetal
life, infancy, late pre pubescence (8-12 years) and during late adolescence or early
adulthood.11–14 A female with typical signs should be tested for TS. There are some
characteristics that can direct the diagnosis into TS. Female with unexplained
growth failure or pubertal delay; with or without the constellation of the
lymphedema sequence (edema of the hands or feet, nuchal fold, neck webbing, low
hairline and hyperconvex or hypoplastic nails); characteristic facial features such

19
as epicanthal folds, downslanting palpebral fissures, low-set ears and micrognathia;
left-sided cardiac anomalies, especially coarctation of the aorta, bicuspid aortic
valve and aortic stenosis; markedly elevated follicle-stimulating hormone (FSH);
cubitus valgus; multiple pigmented nevi; bone anomalies including short fourth
metacarpal/ metatarsal, Madelung deformity and scoliosis; chronic OM and
conductive or sensorineural hearing loss or learning disabilities, especially affecting
visuospatial or nonverbal skills and other traits.30,34,35

Prenatal diagnosis
Sex chromosome abnormalities generally can be detected prenatally by chorionic
villous sampling or amniocentesis, by looking at abnormal serum markers or the
presence of multiple anomalies. Ultrasonography can play an important role that
suggests an increased likelihood of TS. In the first trimester, increased nuchal
translucency is common in fetuses with TS, but is also observed in the autosomal
trisomy syndromes an the presence of a frank cystic hygroma, however, makes the
diagnosis of TS more likely.36 Other ultrasound findings suggestive of TS are
coarctation of the aorta and/or left-sided cardiac defects, brachycephaly, renal
anomalies, polyhydramnios, oligohydramnios and growth retardation.32 Abnormal
triple or quadruple maternal serum screening (alpha-fetoprotein, human chorionic
gonadotropin, inhibin A and unconjugated estriol) may also suggest the diagnosis
of TS, but these tests may be perfectly normal together with normal nuchal fold
thickness.37 Ultrasound and maternal serum screening are not diagnostic, and it’s
an obligation to confirm TS by checking the karyotype.
Fibroblas analysis is reflected by an amniocentesis karyotype reflects
fibroblast analysis but the postnatal outcome and constitutional karyotype of
individuals with prenatally diagnosed 45,X are uncertain, especially in patients with
mosaicism. Therefore, chromosome analysis should be repeated postnatally in all
patients.30,35
Decisions regarding pregnancy termination are difficult, and it is critical that
the best available information is provided to parents. Physicians and genetic
counselors involved in pre- and post-diagnostic counseling need to be fully

20
informed about the prognosis, complications and QoL of individuals affected with
TS, as well as of recent advances in management.3716,38

Postnatal Diagnosis
The American College of Medical Genetics recommendation for all individuals
with suspected TS should have a standard 20-cell karyotype that will identify at
least 10% mosaicism with 95% confidence in the blood.16,38 A peripheral blood
karyotype is usually adequate but if an individual has a normal blood karyotype or
low-level mosaicism, we could use another tissue, such as skin fibroblasts, buccal
mucosa cells or possibly urine for bladder epithelial cells, to be examined.
Sometimes a formal karyotype should be repeated in some conditions such as all
infants diagnosed prenatally should have a postnatal karyotype to confirm the
findings, those diagnosed by a buccal swab only, individuals with a karyotype
performed in the distant past or when no original report is available for review.

Newborn Screening
Missed and delayed diagnoses of TS remain a major problem. For girls with TS
who are not identified in infancy with lymphedema and webbed neck, diagnosis is
often made years after growth failure is apparent, and sometimes when little or no
growth potential remains.11,12,14,39 In general, the later GH therapy is initiated, the
greater the height deficit and the lower the likelihood of normal adult stature and
age-appropriate initiation of therapies for pubertal development. Early diagnosis
allows for timely screening and intervention for problems such as strabismus,
hearing loss, renal and cardiac abnormalities, hypothyroidism, celiac disease and
learning disabilities, thus improving QoL.
Karyotyping is considered to be the gold-standard technique for diagnosing
TS but has major limitations as a screening tool given its long processing time, high
cost, and requirement for specialized personnel. However, several molecular
methods have been proposed for neonatal screening of TS, of which
pyrosequencing and real-time PCR appear to hold the greatest promise.4 Advances
in pyrosequencing technology have been rapid, but it remains expensive40

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Examination
Girls with TS are at increased risk of obesity, elevated cholesterol, diabetes,
hypertension, stroke and ischemic heart disease. During this transition period, the
importance of preparation for adulthood cardiovascular care is emphasized with the
aim of ensuring guideline-driven care and a reduction in morbidity and loss to
medical follow-up.6
The typical neurocognitive profile, personality type and difficult social
adjustment observed in TS pose psychosocial risk that, if not addressed during
transition, can impact QoL. It is also important for pediatric providers to ascertain
that educational and career goals align with the abilities of the individual TS young
woman and to provide appropriate counseling as needed.6

Table 3. Recommendations for screening in Turner syndrome at diagnosis and throughout

life.6

A comprehensive ophthalmological examination between 12 and 18 months

of age or at the time of diagnosis is recommended, if at an older age, with emphasis
on early correction of refractive errors. Refractive errors are present in about 40%
of girls and women with TS, with increased prevalence of both hyperopia and
myopia. Importantly, strabismus and amblyopia each occur in roughly one-third of

22
females with TS. Ptosis (16%), epicanthal folds, hypertelorism and downward-
slanting palpebral fissures are also common. The prevalence of red-green color
blindness is similar to that of males (8%). Multiple visual deficits are found in about
35% those with TS. Early detection and correction of refractive errors are vital to
prevent vision loss.6
Careful follow-up during early childhood, at least annually, is necessary to
detect middle-ear disease and prevent sequelae. In addition, periodic examinations
throughout the lifespan are mandatory even after the resolution of the middle-ear
disease to detect SNHL. Continuous long-term follow-up is indicated for those with
history of cholesteatoma surgery because of a high recurrence rate.6
An infant or child should be examined with transthoracic echocardiography
(TTE) at the time of diagnosis, even if the fetal echocardiogram or postnatal cardiac
examination was normal.6 Congenital coronary arterial anomalies are prevalent in
TS. The left coronary artery is most often affected, with an absent left main
coronary artery being the most frequent anomaly. In addition, single cases of
coronary arterial anomalies have been reported, which include coronary arterial
dilatation, single coronary ostium, coronary arteries originating from the thoracic
aorta, and coronary artery–to–pulmonary artery fistulas. Whether cor`onary arterial
malformations increase mortality risk is unknown. The majority of the encountered
coronary arterial anomalies in TS are benign or noninterarterial; however, it is
important for the cardiothoracic surgeon to be aware of unusual coronary anatomy
because it may necessitate modifications of the operative approach.41

Picture 14. Suggested monitoring protocol for girls with Turner syndrome from infancy to
15 years of age.41
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 Picture 15. Suggested cardiac monitoring protocol for girls and women with TS above
16 years of age.41

Treatment
a. Growth hormone
The latest guidelines recommend starting at 45–50 µg/ kg/day and possibly
increasing up to a dose of 68 µg/kg/day (if the initial response is suboptimal),
administered subcutaneously seven days a week, preferably at night.3 Height
should be monitored every 3–4 months in the first year of therapy and every 4–
6 months thereafter and GH can be discontinued after linear growth is complete
(bone age of approximately 13.5 to 14 years; height velocity <2cm/year).6

b. Estrogen
Oxandrolone is suggested to be used concomitant with GH treatment for children
from the age of 10 years or older than at 0.03mg/kg/day and maintained below
0.05mg/kg/day, if the diagnosis of TS and therefore GH treatment initiation is
delayed, and/or adult height outcome is likely to be unsatisfactory if the
treatment only with standard GH dose. Estrogen replacement should start
between 11 and 12 years of age increasing to adult dosing over 2-3 years.6
Potential side effects of oxandrolone are a slight risk of virilizing effects (acne,
clitoromegaly). If oxandrolone is used concomitantly with GH may improve
adult height by 2-5cm.5

24
 In some cases with ovarian insufficiency, we need to give estrogen/progestin
replacement therapy to achieve adequate breast development, uterine
maturation, and peak bone mass. Gonadotropin especially follicle-stimulating
hormone (FSH) should be monitored annually starting about age 11 years old to
confirm hypergonadotrophic hypogonadism prior to pubertal induction (6) and
also AntiMullerian hormone (AMH) and inhibin B measurements have also been
shown to predict ovarian insufficiency when found to be low, and AMH is
perhaps the best indicator of ovarian reserve.42,43 Transdermal 17-β estradiol
(TDE) is preferred now to treat starting around age 11-12 years.6 Compared with
oral estrogens, TDE is thought to be able to avoid the first-pass effect in the liver
with improved bioavailability.44,45
The lowest doses are available at 14–25 µg TDE patches, which used on a daily
basis after weekly or twice weekly application. Cutting the patches will enable
to start at about 3–7 µg/day, which is the recommended starting dose for pubertal
induction and is gradually increased in 6-month intervals to adult doses (up to a
100 µg/day) by 2–3 years of therapy.6

Complications
a. Cardiovascular abnormalities
An epidemiological study indicated that the overall mortality rate for patients
with TS was 3 times that for the normal population.23 Cardiovascular events
are a major risk factor and occur in 41% of patients. Patients with TS have
congenital cardiovascular abnormalities more often than normal people. Heart
valve disease is a prevalent abnormality, and patients with TS have a
significantly higher incidence of aortic bicuspid deformity. Patients with TS
have a risk of dying mainly from an aortic dissection aneurysm.3
b. Skeletal abnormalities
The mechanism for skeletal fragility in TS is likely multifactorial and has been
attributed to the chromosomal abnormality, acquired osteoporosis, and a higher
propensity to falls due to TS-associated visuospatial cognitive dysfunction,
hearing or visual impairment, and impaired balance.46 Fractures are considered
to be one of the major complications of TS. However, there is currently no

25
 evidence of an increased risk of fracture in children and adolescents with TS,
but there is evidence that women with TS have about a 25% increased risk of
fracture, mainly in the form of forearm fractures.3,32
Hormonal imbalance and intrinsic bone abnormalities result in skeletal fragility
in TS women. Chronic estrogen deficiency due to gonadal failure is a major
modifiable risk factor for osteoporosis, contributing to suboptimal accrual of
peak bone mass. Estrogen prevents bone loss by suppressing bone resorption,
but may also have anabolic effects on bone.46,47
c. Cognitive disturbance
Turner syndrome patients have some learning disabilities, particularly with
regard to spatial perception, visual-motor co-ordination and mathematics. Most
of them are not mentally retarded. Earlier studies on Turner syndrome had
methodological short comings, including faulty reporting of mental retardation
in some patients when in fact, reduced performance IQ in the presence of a
normal verbal IQ results from specific deficits in spatial ability rather than
global reduction in intelligence. Visual-spatial deficits have been related to
reduce functioning in the right cerebral hemisphere, especially the right parietal
lobe.48
Women with mosaic TS 45,X/46,XX has a better IQ than a monosomy TS
syndrome 45,XO. The IQ of girls with 47,XXX is reported to be within the
normal range, but approximately 10–15 points below their sibling average.
Lower IQ is also reported in adult cases of 47,XXX, along with psychosocial
features, such as low self-esteem, language difficulties, and increased
prevalence of psychiatric disorders.53 Assessing disparity in IQ is very
interesting and important in selecting an occupation and thus helping people
lead a productive life. In Turner syndrome patients, this shall be more
important as assessment of verbal IQ- and performance IQ disparity could be
used in helping them select an occupation so that productivity and quality of
life is not grossly compromised.48

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 CASE ANALYSIS
This was a case report of 12 years old girl diagnosed with Turner Syndrome
(TS). Prevalence of 1 in 2000 to 2500 live born female children.5 In Indonesia it
self, TS is considered as rare disease with a very low number of cases. Turner
Syndrome with structural abnormalities of the X chromosome isochromosome X
[46,X,i(X)] has many forms such as, isochromosome is a structural, ring
Chromosome [46,X,r(X)] and deletion (Xp or Xq). Although classic TS karyotype
is 45,X, 30-40% of the remaining have a mosaic pattern with a second cell line
(45,X/46,XX, 45,X/47,XXX, 45,X/46,XY, 45,X/47,XYY and 46,X,delXq).
According to the chromosome examination, our patient is turner syndrome type
45X from chromosome analysis showed 45,XO.
Clinicians need to be alert to the signs and symptoms associated with TS,
especially short stature, subnormal growth velocity, delayed puberty, primary
amenorrhea, or premature ovarian failure. Female with unexplained growth failure
or pubertal delay; with or without the constellation of the lymphedema sequence
(edema of the hands or feet, nuchal fold, neck webbing, low hairline and
hyperconvex or hypoplastic nails); characteristic facial features such as epicanthal
folds, downslanting palpebral fissures, low-set ears and micrognathia; left-sided
cardiac anomalies, especially coarctation of the aorta, bicuspid aortic valve and
aortic stenosis; markedly elevated follicle-stimulating hormone (FSH); cubitus
valgus; multiple pigmented nevi; bone anomalies including short fourth metacarpal/
metatarsal, Madelung deformity and scoliosis; chronic OM and conductive or
sensorineural hearing loss or learning disabilities, especially affecting visuospatial
or nonverbal skills and other traits. Our patient chief complaint was unsatisfied with
her stature, she also complaint about amenorrhea, underdeveloped breasts, and
wasn’t doing well in school. In physical examination, there was a sign of short
stature, wide of papillary mammae distance, low posterior hairline, cubitus valgus,
webbed neck and multiple nevi.
.

27
 Karyotyping is considered to be the gold-standard technique for diagnosing
TS but has major limitations as a screening tool given its long processing time, high
cost, and requirement for specialized personnel. Chromosome analysis was done to
the patient and the result was 45,XO. The result for bone age examination was
Average Girls and appropriate for 10 years old, reproductive hormons test was
normal and our patient was done laboratorium examination tyroid function tes and
hormonal function test. The result for tyroid function test and hormonal function
test was normal.
Therapy for Turner Syndrome should involves growth hormones and other
hormonal therapy. According to latest guidelines, Growth hormone dose start from
45–50 µg/ kg/day and may increase up to 68 µg/kg/day (2 times doses). It
administered subcutaneously, seven days a week, preferably at night.3 The Height
monitored every 3–4 months in the first year of therapy and every 4–6 months then
GH can be discontinued after appropriate linear growth (bone age of approximately
13.5 to 14 years; height velocity <2cm/year). Estrogen is suggested to be used
concomitant with GH treatment for children from the age of 10 years or older than
at 0.03mg/kg/day and maintained below 0.05mg/kg/day. Our patient was treated
with Saizen (Somatropin) 1 x 1.5 mg (in therapeutic dose, she got for 3 months,
result was 2 cm/ 6 months.

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 PEDIATRIC NUTRITIONAL CARE

I. Identity

Name : AS
Age : 14 years old
Gender : Female
Address : Pekanbaru

Diagnosis : Turner Syndrome

Problem : Short stature + wide of papillary mammae distance+
low posterior hairline + cubitus valgus + webbed neck+
multiple nevi

II. Assessment
BW : 33 kg
BH : 134 cm
Ideal BW : 37 kg
HA : 9 years 6 months old
BW/A : 89% (Growth chart turner syndrome)
BH/ A : 100% (Growth chart turner syndrome)
BW/BH : 89% (Growth chart turner syndrome)
Interpretation : Normal limit in Growth chart turner syndrome
III. Requirement
RDA : 60 - 80 kcal/ kgBW/ day
RDA Absolut : BW x RDA = 33 x (60-80) kcal= 1980 – 2640 kcal/day
RDA Ideal : Ideal BW x RDA= 37 x (60-80)= 2220 – 2960kcal/day
BMR : 16,97 x Wt + 161,8 x Ht + 371,2
: 6,25 x 33 + 1023,2 x 1,34 + 371,2
: 2278,5
Stress factor : 1,5
BEE : BMR x stress factor = 3417,7
29
IV. Fluid requirement : 80 - 100 cc/ KgBW/ day
: 33 x (80-100)
: 2640 - 3300 cc / day
V. Type of food : family food
VI. Route : per oral
VII. Nutrition care plan : Family food 51% from BEE
Family food 79% from RDA Ideal

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 Evidenced-Based Medicine
A. Clinical question
What are causes of turner syndrome in infants?
B. Component of foreground question (PICO)
Problems : Genetic factor associated with turner syndrome in infants
Intervention : None
Comparison : The patient no history of prenatal test, according to this
journal children with turner syndrome got detecting sex
chromosome.
Outcome : Whole-genome sequencing of circulating cell-free DNA in
maternal plasma has enabled noninvasive prenatal testing for
common autosomal aneuploidies, including TS (45,X).
However, the incidence of mosaicism may complicate
noninvasive prenatal testing, particularly with respect to
gonadal dysgenesis in the adult female population. In one
study, the combined sensitivity for detecting sex
chromosome aneuploidies was 96.2%, the false positive rate
was 0.3%, and the nonreportable rate was 5%11).
In another report, which excluded mosaic samples, the
results corresponded to a sensitivity of 100% and a
specificity of 99.75% for detecting sex chromosome
aneuploidies12). This method may miss structurally
abnormal X chromosome and mosaicism..

C. Investigation method
Investigation was done based on keywords “Turner syndrome, Diagnosis,
Hormone replacement therapy”. By using limitation of the study in human and
establish within the last 15 years. Founded an article answered the clinical
question with title: Diagnostic and therapeutic considerations in Turner
syndrome on Ann Pediatr Endocrinol Metab (2017): 226-230. Authors:
Seung Yang, MD, PhD

31
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