Genetic/Congenital

Question 1

What defects are seen in trisomy 13 (Patau syndrome)?

Answer 1

Failure to thrive, seizures, cleft lip and palate,
microphthalmia, cutis aplasia of the scalp (congenital absence of skin), congenital heart disease, and severe mental retardation

Question 2

What is cri du chat syndrome?

Answer 2

The distinctive, catlike cry associated with cri du chat syndrome is likely caused by abnormal laryngeal development; it tends to resolve with time. Profound mental retardation, self-injury behavior, hypersensitivity to sound, and repetitive behaviors are commonly seen. Deletion of the short arm of chromosome 5 is the etiology. About 85% of cases are paternal in origin.

Question 3

What is VATER (or VACTERL)?

Answer 3

Commonly seen findings of unknown etiology. The patents affected have vertebral defect, anal atresia, cardiac defects, tracheoesophageal fistula, renal/radial defect (or both), and limb abnormalities. Intelligence is normal.

Question 4

What are features of Cornelia de Lange?

Answer 4

Bushy eyebrows, hirsutism, limb defects, VSD, and mental retardation.

Question 5

What is Wiskott-Aldrich syndrome?

Answer 5

Rare X-linked recessive disease that causes eczema, thrombocytopenia, and immunodeficiency. Can have eosinophilia.
Mnemonic:
Mr Wiskott-Aldrich wears a TIE but [no M]atching shirt.
TIE: Thrombocytopenia, Infections, Eczema.
[no M]: low IgM. (high IgA and IgE)

Question 6

What is choanal atresia?

Answer 6

A congenital disorder where the back of the nasal passage (choana) is blocked, usually by abnormal bony or soft tissue (membranous) due to failed recanalization of the nasal fossae during fetal development. Most neonates are obligate nose breathers and cannot breathe adequately through their mouths. Infants with choanal atresia have increased breathing difficulty during feeding and sleeping and improved respirations when crying.

Question 7

What is the CHARGE association?

Answer 7

Coloboma, Heart disease, Atresia of the choanae, Retarded growth and development, Genital hypoplasia, and Ear abnormalities

Question 8

What are potential complications of cleft lip and palate?

Answer 8

Complications include recurrent otitis media and hearing loss as well as speech defects, which may be present despite good anatomic closure.

Question 9

When are cleft lip and palate generally repaired?

Answer 9

Repair of a cleft lip usually is performed within the first 2 to 3 months of life; the palate is repaired later, usually between the ages of 6 months and 5 years.

Question 10

What is the Potter sequence?

Answer 10

Dysmorphic child (widely spaced eyes, low set ears, broad nose, receding chin, limb abnormalities) and bilateral renal agenesis. These infants have immediate respiratory distress due to primary pulmonary hypoplasia

Question 11

What is Waardenburg syndrome?

Answer 11

It is inherited as an autosomal dominant trait with variable penetrance. It includes, in decreasing order of frequency, the following anomalies: lateral displacement of the medial canthi, broad nasal bridge, medial hyperplasia of the eyebrows, partial albinism commonly expressed by a white forelock or heterochromia (or both), and deafness in 20% of cases.

Question 12

What is Sturge-Weber syndrome?

Answer 12

STURGE: seizures, trigeminal port-wine stain/tram track calcifications on gyri, unilateral weakness (hemiparesis), retardation in some, glaucoma, eye problems (e.g. buphthalmos = eye enlargement)
Neurologic symptoms occur on the side OPPOSITE the port wine stain. These could be seizures or hemiparesis.

Question 13

What mnemonic is helpful for remembering tuberous sclerosis?

Answer 13

HAMARTOMA:
Hamartoma
Adenoma sebaceum
Mitral regurgitation
Ash-leaf spots
Rhabdomyoma
(Tuberous sclerosis)
dOminant inheritance
Mental retardation (65%)
Angiomyolipoma (of kidney)

Question 14

What is Noonan syndrome?

Answer 14

Noonan syndrome, the “male Turner syndrome,” occurs in both sexes. The most common features include short stature, downslanting palpebral fissures, ptosis, low set and malformed ears, webbed neck, shieldlike chest, pulmonic stenosis, and cryptorchidism. Mental retardation is seen in one-fourth of affected individuals. It is associated with advanced paternal age.

Question 15

What is thrombocytopenia-absent radius (TAR) syndrome

Answer 15

Diagnosed in the newborn who demonstrates profound thrombocytopenia, bilateral absence of radius, and abnormally shaped thumbs. Cardiac lesions include TOF
and ASD. About 40% of patients die in the newborn period as a result of low-platelet-induced bleeding.

Question 16

What syndrome is associated with prolonged QT and deafness?

Answer 16

Jervell-Lange-Nielsen syndrome (autosomal recessive)

Question 17

What is prune belly syndrome?

Answer 17

It is a malformation that occurs mostly in males and is characterized by a lax, wrinkled abdominal wall (lack of abdominal muscle tone), a dilated urinary tract, intra-abdominal testicular, and significant renal dysfunction or dysplasia leading to oligohydramnios and commonly associated pulmonary complications, such as pulmonary hypoplasia and pneumothorax. Congenital hip dislocation, clubfeet, and intestinal malrotation with possible secondary volvulus can occur. There does not appear to be a genetic predisposition to prune belly syndrome.

Question 18

What are the manifestations of Alport syndrome?

Answer 18

X-linked dominant (males more heavily affected). Hearing loss and deafness, hematuria especially after URIs, ESRD by second or third decade of life is common, ocular abnormalities in 30-40%, and rarely leiomyomas of the esophagus and respiratory tree

Question 19

What is homocystinuria?

Answer 19

AR, deficiency of cystathionine β-synthase. Manifestations include poor growth, arachnodactyly, osteoporosis, dislocated lenses, and mental retardation. In addition, thromboembolic phenomena may be seen in the pulmonary and systemic arteries and particularly in the cerebral vasculature (e.g. infantile stroke).

Question 20

What muscle groups are primarily affected in myotonic dystrophy?

Answer 20

Distal muscle weakness is a key feature (as opposed to other muscular dystrophies which usually cause proximal muscle weakness)

Question 21

What is diagnostic criteria for NF1 (mutation of chr 17)?

Answer 21

The presence of any two of the following findings confirms the diagnosis of NF1: (1) Five or more café au lait spots over 5 mm in diameter in prepubertal patients; six or more over 15 mm in diameter in postpubertal patients; (2) axillary freckling; (3) two or more Lisch nodules (hamartomas of the iris); (4) two or more neurofibromas, typically involving the skin and appearing during adolescence or pregnancy, or one plexiform neuroma involving a nerve track present at birth; (5) bony lesions leading to pathologic fracture and kyphoscoliosis; (6) optic glioma; (7) NF1 in a first-degree relative.

Question 22

What is usually the cause of death in Reye syndrome?

Answer 22

Death is usually from cerebral edema and subsequent herniation.

Question 23

What is PHACES syndrome?

Answer 23

Posterior fossa malformations–hemangiomas–arterial anomalies–cardiac defects–eye abnormalities–sternal cleft and supraumbilical raphe syndrome. Hemangiomas linked with PHACE Syndrome tend to cover a large area of the face, head or neck, either as one lesion or as many single lesions.

Question 24

What is Beckwith-Wiedemann syndrome?

Answer 24

At birth infants have macrosomia with macroglossia, abdominal wall defects, linear ear creases, and organomegaly; they often have hypoglycemia in the newborn period. They have an increased incidence of developing malignancy, especially Wilms tumor,
hepatoblastoma, and gonadoblastoma. Intellect is usually normal.

Question 25

What is Crouzon syndrome?

Answer 25

An autosomal dominant condition that results in craniosynostosis (usually coronal), proptosis, brachycephaly, hypertelorism and strabismus, “beak” nose, midface hypoplasia, and high and narrow palate.

Question 26

What is Jeune syndrome (asphyxiating thoracic dystrophy)?

Answer 26

It is notable for short stature, long and narrow thorax, hypoplastic lungs, fibrotic liver, and short limbs. Death is common, a result of pneumonia or asphyxia because of the abnormally shaped thorax.

Question 27

What is Menkes syndrome?

Answer 27

Presents in the first months of life and includes hypothermia, hypotonia, and myoclonic seizures. These children have chubby, rosy cheeks and kinky, colorless, and friable hair. Severe mental retardation is always seen. Low serum copper and ceruloplasmin levels are found, with a copper absorption/transport problem being the cause.

Question 28

What is Laurence-Moon-Biedl (Bardet-Biedl) syndrome?

Answer 28

AR disorder. Characterized by obesity, mental retardation, hypogonadism, polydactyly, and retinitis pigmentosa with night blindness.

Question 29

What is Holt-Oram syndrome?

Answer 29

Characterized by abnormalities in the upper extremities, hypoplastic radii, thumb abnormalities, and cardiac anomalies (VSD and 1st degree heart block). Occasionally the pectoralis major muscle is missing

Question 30

What are features of Edwards syndrome (trisomy 18)?

Answer 30

Babies are small with low-set ears, a prominent occiput, a short sternum, a closed hand with overlapping fingers, cardiac defects, rocker-bottom (rounded) feet, cleft lip and/or palate, and renal and genital abnormalities. Mortality is 50% in the first week and 90% in the first year.

Question 31

What does MELAS stand for?

Answer 31

Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes

Question 32

What are the characteristic features of neurofibromatosis 1?

Answer 32

Café au lait spots, macrocephaly, feeding problems, short stature, learning disabilities, and freckling in the armpits and groin. Neurofibromas and other fibromas may develop later. Defect on chr 17

Question 33

What are characteristic features of neurofibromatosis 2?

Answer 33

Bilateral acoustic neuromas and cataracts. Can also develop fibromas and neurofibromas. Defect on chr 22

Question 34

What are the characteristics of Beckwith-Wiedemann syndrome?

Answer 34

Caused by a defect of chr 11p15 (codes for insulin-like growth factor 2). This leads to the classic findings of macrosomia, macroglossia, hemihyperplasia, and medial abdominal wall defects (e.g. umbilical hernia, omphalocele). Infants also have hypoglycemia and are at significantly increased risk for Wilms tumor and hepatoblastoma.

Question 35

What surveillance measures should be in place for infants and children with Beckwith-Wiedemann syndrome?

Answer 35

Newborns require close monitoring of blood glucose (have fetal hyperinsulinemia). This is usually a transient problem and older asymptomatic patients no longer require BG monitoring. Patients should also receive screening abdominal ultrasounds and alpha-fetoprotein levels every 3 months from birth to age 4 years, abdominal ultrasound every 3 months from age 4-8 years, and then renal ultrasounds from age 8 through adolescents to monitor for neoplasia (heptoblastoma and Wilms tumor)

Question 36

Compare the lens dislocation in Marfan syndrome to homocystinuria?

Answer 36

Marfan’s: upwards dislocation

Homocystinuria: downwards dislocation

Question 37

What is the main feature of galactokinase deficiency?

Answer 37

Bilateral cataracts, otherwise asymptomatic

Question 38

What is Werdnig-Hoffman syndrome?

Answer 38

“Floppy baby” syndrome - degeneration of the anterior horn cells