Syndromes

Question 1

TAR syndrome

Answer 1

Thrombocytopenia with absent radii
Autosomal recessive
Severe thrombocytopenia (absent/reduced megakaryocytes)
B/L absent radii and ulnar abnormalities- thumbs and digits are normally developed
Can have cardiac anomalies and facial capillary hemangioma
Has gradual increase in platelet count, leading cause of death ICH

Question 2

Kasabach-Merritt syndrome

Answer 2

Skin lesions resembling hemangiomas (may be multiple or single) - consistent with hemangioendotheliomas
May lead to high output cardiac failure, DIC, thrombocytopenia

Question 3

Tuberous Sclerosis

Answer 3

Autosomal dominant
Hypopigmented ashleaf spots (Wood's lamp)
Intracranial tumors
Eye involvement
Seizures
Mental deficiency
Enamel pits
Cardiac rhabdomyomas

Question 4

Schwachman-Diamond syndrome

Answer 4

Autosomal recessive, chromosome 7
Pancreatic insufficiency - malabsorption
Short stature
Bone marrow dysfunction (neutropenia is most common)
Diarrhea
Normal bicarb
Negative sweat test
Increased risk of myelodysplastic syndromes, leukemia

Rx: pancreatic enzymes, Vit A, D, E, K, increased calories and GCSF

Question 5

Cystic fibrosis

Answer 5

Mutation in 508, chromosome 7
Abnormality in protein used for chloride transport (CFTR)
Vit K malabsorption
Diarrhea
Rectal prolapse
Nasal polyps
Increase chloride in sweat, >50
Need to confirm an increased IRT with mutational analysis

Question 6

SMA type 1 (Werdnig Hoffman)

Answer 6

Autosomal recessive, chromosome 5
Degeneration of anterior horn cell
Generalized hypotonia
Frog leg and jug handle position
Bulbar weakness, facial sparing
Death <2 years
Muscle biopsy with motor unit atrophy
Normal nerve conduction velocity

Question 7

Congenital myotonic dystrophy

Answer 7

Autosomal dominant, chromosome 19
Expanded CTG repeat (triple repeats) -> dysfunctional sodium and potassium channels
Severity increases with increasing number of repeats
Inherited from mother
Abnormal muscle biopsy (small and round muscle fibers with large nuclei and sparse myofibrils)

Question 8

Sturge-Weber syndrome

Answer 8

Port wine stain, 1st division of trigeminal nerve
Tramline intracortical calcifications ipsilateral
Glaucoma, vision defects
Seizures
Hemiparesis contralateral to facial lesion

Question 9

Tuberous sclerosis

Answer 9

Autosomal dominant (chromosome 9, 16)
Hypopigmented ash leaf spots (Wood's lamp), greatest on trunk and buttocks
CNS tumors
Cardiac rhabdomyomas
Seizures
Enamel pits in teeth

Question 10

Neurofibromatosis

Answer 10

Autosomal dominant, Chromosome 17
Cafe au lait
Freckling in axilla
Cutaneous neurofibromas, schwannoma, pheochromocytomas

Question 11

McCune-Albright syndrome

Answer 11

Brown pigmentation
Fibrous dysplasia of bones
Precocious puberty
Pituitary adenomas

Question 12

von Hippel-Lindau

Answer 12

Autosomal dominant, chromosome 3
CNS tumors (most commonly in the cerebellum)
Systemic hemangiomas
Retinal angiomas
Pheochromocytomas

Question 13

Chediak-Higashi

Answer 13

Abnormal neutrophil degranulation
Oculocutaneous albinism
Nystagmus
Peripheral neuropathy
Recurrent infections
WBC inclusions

Question 14

Reticular dysgenesis

Answer 14

Lymphopenia
Fatal bacterial or viral infections
Bilateral sensorineural deafness

Question 15

Beckwith Weidemann

Answer 15

Chromosomal 11 issue, of paternal uniparental disomy
Large tongue
Exophthalmus
Macrosomia
Hypoglycemia
Intrabdominal malignancies

Question 16

CHARGE syndrome

Answer 16

Autosomal dominant CHD 7 (but may also not be detected)
Coloboma (major)
Heart defect
Choanal Atresia (major)
Renal anomalies, growth Restriction
Genital hypoplasia
Ear abnormalities (major)

Risk for motor delays, hypotonia, visual and vestibular abnormalities

Question 17

VACTERL association

Answer 17

No known cause
Vertebral anomalies
Anal atresia
Cardiac (VSD most common)
TE fistula
Renal anomaly
Limb dysplasia

Question 18

Apert syndrome/Acrocephalosyndactyly

Answer 18

Autosomal dominant, defect in FGF2
Increased paternal age
Irregular craniostynostosis (esp coronal)
Hypertelorism
Midfacial hypoplasia
Broad distal phalanxes of thumbs, big toes

Question 19

Crouzon syndrome/Craniofacial dysostosis

Answer 19

Autosomal dominant, FGF2
Premature craniosynostosis
Parrot beak nose
Maxillary hypoplasia
Shallow orbits

Question 20

Osteogenesis Imperfecta

Answer 20

COL1A gene: can be AD or AR

Type 2 most severe, lethal because of respiratory failure

Question 21

Thanatophoric dysplasia

Answer 21

Autosomal dominant, FGF3
Severe, death from respiratory failure
Narrow thorax, hypoplastic lung
Short limbs
Depressed nasal bridge
Telephone receiver long bones (type 1)
Cloverleaf skull (type 2)

Question 22

Achondroplasia

Answer 22

Autosomal dominant, FGF3
Short limbs, normal trunk
Trident hand
Cone shaped phalanges
Decreasing distance between vertebra seen on AP spine XR
Live until adulthood, normal intelligence

Question 23

Stickler syndrome

Answer 23

Autosomal dominant FGF2
Midface hypoplasia
Micrognathia
Pierre Robin
Sensorineural hearing loss
Myopia
Retinal detachment

Question 24

Fragile X syndrome

Answer 24

X linked dominant
Loss of function mutation due to expansion of CGG repeats
50-200 premutations -> women with premature ovarian failure

Long narrow face, prominent forehead
Macrocephaly
Large ears
Large testes

Question 25

Williams syndrome

Answer 25

``` 7q11.23 gene deletion, elastin gene mutation Supravalvular subaortic stenosis Hypoplastic nails Prominent lips Stellate iris pattern Mental deficiency Transient hypercalcemia ```

Question 26

WAGR syndrome

Answer 26

``` 11p13 deletion Wilms tumor Aniridia Genitourinary abnormalities Mental deficiencies ```

Question 27

Rubenstein-Taybi syndrome

Answer 27

``` 16p13.3 deletion: CREB Cardiac anomalies Broad thumbs and toes Downward slanting palpebral fissures Postnatal growth deficiency Developmental delay Increased risk of tumors ```

Question 28

Smith Lemli Opitz syndrome

Answer 28

``` Autosomal recessive Defect in cholesterol synthesis: low cholesterol, high 7-dehydrocholesterol 2nd and 3rd toe syndactyly Anteverted nostrils Genital anomlies (failure of masculinization) Mental deficiency FTT High mortality ```

Question 29

Zellweger Syndrome

Answer 29

``` Autosomal recessive, defects in PEX genes Peroxisomal biogenesis disorder: accumulation of VLCFA Postnatal growth deficiency Issues with brain development Large fontanels, flat occiput Anteverted nares Congenital cataracts Albuminuria Equinovarus deformity ```

Question 30

Legius syndrome

Answer 30

``` Autosomal dominant Cafe au lait macules (like NF-1) Axillary or inguinal freckling Macrocephaly Learning disabilities ```

Question 31

Cartilage-hair hypoplasia

Answer 31

``` Autosomal-recessive, mutation of the RMRP gene on chromosome 9p13 Short-limbed dwarfism Hypotrichosis (fine, light hair) Immune deficiency Hirschsprung's ```

Question 32

Leigh syndrome

Answer 32

Mitochondrial

Question 33

Lowe syndrome

Answer 33

``` X-linked, OCRL gene Oculocerebrorenal syndrome Congenital cataracts Hypotonia Renal failure Severe intellectual impairment ```

Question 34

Cornelia de Lange

Answer 34

``` Single nucleotide mutation in a gene coding for a protein in the cohesin pathway Very high incidence of severe gastroesophageal reflux disease and malrotation with the potential for volvulus Microcephaly Hypertonicity Curly long lashes Synophrys High arched palate Hirsuitism Limb abnormalities ```

Question 35

Trisomy 8

Answer 35

Deep creases Thick lips Camptodactyly Prominent cupped ears

Question 36

Cri du chat

Answer 36

``` 5p deletion (paternal origin) Downward slant of palpebral fissures Severe mental deficiency Cat like cry FTT ```

Question 37

Wolf Hirschhorn

Answer 37

``` 4p deletion Greek warrior helmet Hypertelorism Broad or beaked nose Cranial asymmetry ```