Lascano, Joanne Alyssa

3J
Pediatrics 3B Small Group Discussion Cases 1-3 Developmental Disorders
Clinical Vignette 1
A term, male, was delivered via NSD. Physical examination showed brachycephaly with upward
slanting of the palpebral fissures, low set ears, large tongue, a short neck, and simian crease on
the left palmar area.

1. What is your main impression?

Main impression: Down Syndrome or Trisomy 21.

Down syndrome occurs in about 1:700 newborns. Cognitive disabilities in the
mild to moderate range are characteristic of Down syndrome, as is generalized
hypotonia. The affected newborn may have prolonged physiologic jaundice. and
transient blood count abnormalities. Feeding problems and constipation are common
during infancy. Problems which may develop during childhood include thyroid
dysfunction, visual issues, hearing loss, obstructive sleep apnea, celiac disease, atlanto-
occipital instability, and autism.

Salient features present in this case are the craniofacial features mentioned like
brachycephaly, upward slanting of the palpebral fissures, low set ears, large tongue, a
short neck, and simian crease observed on the left palmar area.

2. What causes this? List all and discuss.

o Abnormalities in Chromosomal Number: Trisomy is the most common
numerical chromosomal abnormalities found in human; nondisjunction in cell
division that results in the presence of an extra copy of chromosome 21; an error
during the formation of the egg or the sperm results in either one having an extra
chromosome; errors in cell division
 As a result of nondisjunction, the fertilized egg contains three copies of
chromosome 21 (trisomy 21); using standard cyto-genetic nomenclature,
trisomy 21 is designated 47,XX,+21 or 47,XY,+21. In 4.5% of cases, the
extra chromosome is part of a robertsonian translocation, which
occurs when the long arms (q) of two acrocentric chromosomes (numbers
13, 14, 15, 21, or 22) fuse at the centromeres, and the short arms (p),
containing copies of ribosomal RNA, are lost.
  The most common robertsonian translocation leading to DS involves
chromosomes 14 and 21; standard nomenclature is 46,XX,t(14q21q) or
46,XY,t(14q21q).
 Mosaicism: In 1-2% of children with DS, mosaicism occurs. These
individuals have two populations of cells: one with trisomy 21 and one
with a normal chromosome complement. Mosaicism results either from a
non disjunctional event that occurs sometime ater fertilization or from
trisomic rescue.
o Maternal Factors: advance maternal age - maternal age specifically those
mothers bearing a child at age 35 or older, maternal exposure to teratogen or
toxins that affects cell growth

o Genetics: genetics play a role in transmission of down syndrome gene to

offspring; The parents of infants with DS who have translocations should have a
karyotype to exclude a balanced
o
o 􏰀  Mosaic trisomy 21: Not every cell in the body is exactly the same. In a small
percentage (less than 5%) of Down syndrome cases, most of the cells in the
body have the extra chromosome, but some of them don't. This is called
"mosaicism." Mosaic trisomy 21 can occur when the error in cell division takes
place early in development but after a normal egg and sperm

c. Enumerate the anticipated comorbidities of the case.

 Congenital Heart defects - Almost half of all children with DS have congenital heart
disease, including atrioventricular canal, ventriculoseptal or atrioseptal defects, and
valvular disease; isolated secundum atrial septal defects, isolated secundum atrial
septal defects, patent ductus arteriosus, and tetralogy of Fallot
 Gastrointestinal: Between 5% and 10% of newborns with DS have gastrointestinal tract
anomalies. The three most common defects are duodenal atresia, annular pancreas,
and imperforate anus.
 Endocrine: Four percent to 18% of infants with DS are found to have congenital
hypothyroidism, which is identified as part of the newborn screening program. Acquired
hypothyroidism is a more common problem. Thyroid function must be monitored
periodically during the child’s life; Diabetes mellitus
 Hematologic and Immunology: Polycythemia at birth (hematocrit levels >70%) is
common and may require treatment. Some infants with DS show a leukemoid reaction,
with markedly elevated white blood cell; megakaryoblastic leukemia, immune
dysfunction
 Pulmonary sequalae: recurrent respiratory infections, sleep disordered breathing,
laryngo- and trachea-bronchochomalacia, tracheal bronchus, pulmonary hypertension,
and asthma
 Other problems: visual issues, hearing loss, obstructive sleep apnea, celiac disease,
atlanto-occipital instability, and autism, Alzheimer’s disease, Seizures, Alopecia,
Juvenile idiopathic arthritis

d. How will you manage this patient at present and as he gets older?

o In Down syndrome, for example, 79% of the malformations detectable by clinical

examination are minor anomalies. When thediagnosis of Down syndrome is
made, the“whole” (i.e., the constellation of minor anomalies) is more important
than the sum of the individual parts.
 o Take a careful history and perform a thorough but focused physical examination,
using your indings to form a diag- nostic hypothesis and plan.
o Surgical emergencies if not contraindicated especially for bowel obstruction must
be identified rapidly in children with acute abdominal pain. Common
distinguishing characteristics include pain that is accompanied by vomiting,
tenderness, abdominal wall rigidity, or guarding.
o Hematologic Workups and Screening since patient is prone to blood disorders
o Endocrine Workups and Monitoring to prevent further complication since patient
with Down syndrome usually has thyroid problems

e. Create an infographic about the case as to etiology, manifestations, and

complications.
Small Group Discussion Cases 1-3

Developmental Disorders
Clinical Vignette 2
MY is an 18-month-old, male, who was brought in due to fever and colds. He was quiet and
did not turn to sound or name calling. He preferred to be carried by his mother and gestured to
indicate needs. His mother shared that he is usually an active boy at home and loves to play
with his older siblings. But he did not respond when called even when a very loud voice was
used and would point to communicate. The birth and maternal, past medical and family history
were non-contributory.
 1. What is your initial impression?
Autism Spectrum Disorder - Hallmarks of ASD include impaired communication and
impaired social interaction as well as stereotypical behaviors, interests, and activities.
Intellectual disability is common (~38% according to Centers for Disease Control and
Prevention [CDC] estimates); although the majority of children demonstrate average to
high intelligence scores, they often show uneven abilities.

ASD is seen in approximately 1% of the population with equal prevalence rates among
all racial and ethnic groups. Boys appear to be diagnosed much more frequently than
girls (4 : 1 ratio); however, girls with the disorder tend to be more severely affected
regarding intellectual abilities and symptom severity. ASD is characterized by lifelong
marked impairment in social interaction and social communication in addition to RRPBs.
Approximately 20% of parents report relatively normal development until 1-2 years of
age, followed by a steady or sudden decline. In infants with ASD there is delayed or
absent social smiling.

2. List 3 differential diagnoses and basis for each.

o Anxiety disorder (Selective mutism) –a complex when a child's inability to
speak and communicate effectively in select social settings
o Attention Deficit Hyperactivity Disorder – a suspected hearing impairment that
may possibly contribute to the child’s deficit and gain of attention
o Communication Disorder – present with difficulty in social interaction, self
expression, and response when called by their name, following instructions or
communication as observed in the case where the child only gestured to express
his needs

3. How will you manage the case?

NON - PHARMACOLOGICAL
 o A variety of nonpharmacological interventions exist for ASD. Such interventions have
largely fallen under the classification of behavioral training.
o Models have typically employed therapies individually tailored for children with ASD and
their families/caregivers.
o Evidence suggests that useful therapies have included techniques from applied behavior
analysis (ABA), discrete trial training (DTT), functional behavioral analysis (FBA), and
structured teaching (TEACCH Model).
o Behavioral management training for parents has also demonstrated efficacy in helping
with unwanted behaviors. Special education services should be individualized for the
child.
o Occupational, speech, and physical therapy are often required. Referral for disability
services and support is often warranted.
o Family support groups and individual supportive counseling for parents is useful. he
prognosis for ASD is guarded and varies greatly from child to child. here are no known
methods of primary prevention. Treatment and educational interventions are aimed at
decreasing morbidity and maximizing function.

PHARMACOLOGICAL

o Treatment of ASD is typically multimodal. At present, there are no

pharmacological treatments for the core symptoms of ASDs.
o Antipsychotics (risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone,
paliperidone, haloperidol, thioridazine) are used for aggression, agitation,
irritability, hyperactivity, and self-injurious behavior.
o Anticonvulsants have also been used for aggression.
o Naltrexone has been used to decrease self-injurious behavior, presumably by
blocking endogenous opioids.
o Selective serotonin reuptake inhibitors are given for anxiety, perseveration,
compulsions, depression, and social isolation.
o Stimulants are useful for hyperactivity and inattention; however, there are reports
of significant worsening of irritability and aggression in some patients treated with
stimulants.
o Alpha-2 agonists (guanfacine, clonidine) are used for hyperactivity, aggression,
and sleep dysregulation, although melatonin is first-line medication for sleep
dysregulation.

4. What are the associated comorbidities for this case? Discuss.

o Common psychiatric co-morbidities include:

o intellectual disability, language/communication disorders, anxiety disorders,
attention-deficit/hyperactivity disorder, developmental coordination disorder, and
depressive disorders.
o Other medical complexities commonly seen in children with ASD include seizure
disorder, sleep disorders, and gastrointestinal disorders (constipation, food selectivity).
o Intellectual abilities and language abilities are the strongest predictors of improved long-
term prognosis. he earliest studies of autism suggested a relatively poor prognosis, with
only a small number of individuals (1-2%) being able to function independently as adults.
Small Group Discussion Cases 1-3
Developmental Disorders
Clinical Vignette 3

A 9-month-old was rushed to the emergency room because of seizures. Physical

examination showed hypopigmented macules over the body with a hyperpigmented patch over
the left lower extremity.

a. What is your working diagnosis?

Tuberous Sclerosis Tuberous sclerosis complex (TSC), an autosomal-dominant disorder,

is characterized by hamartomas in many organs, especially the brain, eyes, skin, kidneys, and
heart. he incidence is 1 in 10,000 births. Two thirds of cases are sporadic and thought to
represent new mutations. Germline mosaicism is uncommon but explains how parents who
apparently do not have the disease can have multiple children with tuberous sclerosis.
Mutations affecting either of the presumed tumor suppressor genes, TSC1 or TSC2, cause
tuberous sclerosis.

Salient features from present in the case are seizures, hypopigmented macules all over
the body, and the accompanying hyperpigmented patch on the left lower extremity.

b. List 3 differential diagnoses and basis for each.

o Nonfebrile seizure: Rule in: 9 month old, rushed to emergency room because of
seizures, no history of fever: Rule out: hypopigmented macules over body with
hyperpigmented patch over left lower extremity
o Hemangioma: Hemangiomas of early infancy may look similar to the forehead
plaque or shagreen patch in infants but rapid growth of the hemangioma over
theensuing days to weeks will distinguish between these lesions.
o Neurofibromatosis type 1 (NF1) - a multisystem genetic disorder that is
characterized by cutaneous findings, most notably café-au-lait spots and axillary
freckling, by skeletal dysplasias, and by the growth of both benign and malignant
nervous system tumors, most notably benign neurofibromas.

c. How will you manage this case?

o Therapy is as indicated by underlying disease ( eg. seizures and tumors of the

brain, kidney, and heart).
o Treatment of refractory epilepsy may lead to surgical extirpation of epileptiform
tuber sites. Skin lesions on the face may need dermabrasion or laser treatment.
Genetic counseling emphasizes identification of the carrier.
o The risk of appearance in offspring if either parent is a carrier is 50%. The patient
should be seen annually for counseling and reexamination in childhood.
Identification of the chromosomes (9,16; TSCl and TSC2 genes) may in the
future make intrauterine diagnosis possible.
o Imaging Studies and Special Tests
o Plain radiographs may detect areas of thickening within the skull, spine,
and pelvis, and cystic lesions in the hands and feet.
o Chest radiographs may show lung honeycombing.
o Head CT scan may show the virtually pathognomonic calcified
subependymal nodules;
 o Brain MRI may show hypomyelinating white matter lesions, brain tumors,
widened gyri, or cortical tubers. EEG should be considered in any TSC
patient with new-onset spells concerning for seizures.

d. What are the associated comorbidities for this case? Discuss.

TSC has a wide phenotypic expression, from asymptomatic carriers to patients with
refractory epilepsy and significant intellectual disability. Seizures in early infancy, such as infan
tile spasms, correlate with developmental delay. The triad of seizures, intellectual disability,
and adenoma sebaceum occurs in only 33% of patients.

1. Dermatologic -Skin findings bring most patients to the physician's attention Ninety six
percent of patients have one or more hypomelanotic macules, facial angiofibroma’s, ungual
fibromas, or shagreen (leathery orange peel) patches. Adenoma sebaceous (facial skin
hamartomas) may first appear in early childhood, often on the cheek, chin, and dry sites of the
skin where acne is not usually seen. Ash-leaf spots are off-white hypomelanotic macules, are
often oval or "ash leaf' in shape, and follow the dermatomes. A Wood lamp (ultraviolet light)
shows the macules more clearly. The equivalent to an ash leaf spot in the scalp is poliosis
(whitened hair patch). Subungual and periungual fibromas are more common in the toes.
Fibrous or raised plaques may resemble coalescent angiofibroma’s. Cafe au lait spots are
occasionally seen.

2. Neurologic features- Seizures are the most common neurologic sequela. Virtually any kind
of symptomatic seizure (eg, atypical absence, partial complex, and generalized tonic-clonk
seizures) may occur. Up to 20% of patients with infantile spasms have TSC. Thus, any patient
presenting with infantile spasms should be evaluated for TSC. Intellectual dis ability occurs in up
to 50% of patients referred to tertiary care centers; the incidence is probably much lower in
randomly selected patients.

3. Renal lesions- Renal cysts or angiomyolipomas may be asymptomatic, though hematuria or

obstruction of urine flow sometimes occurs. Ultrasonography of the kidneys should be done in
any patient suspected of TSC, both to aid in diagnosis if lesions are found and to rule out
renal obstructive disease.

4. Cardiopulmonary involvement- Rarely, cystic lung disease may occur. Cardiac

rhabdomyomas may be asymptomatic but can lead to outflow obstruction, conduction
difficulties, and death. Cardiac rhabdomyoma may be detected on prenatal ultrasound
examination or postnatal chest radio graphs or echocardiograms. Rhabdomyomas typically
regress with age; thus, symptomatic presentations are typically in the perinatal period.

5. Eye involvement- Retinal hamartomas are often near the disk and are usually
asymptomatic.

6. Skeletal Involvement- Cystic rarefactions can be found in the bones of the fingers or toes.

REFERENCES:

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