Genetic Disorders

Question 0

Crouzon Syndrome

Answer 0

AD, incomplete penetrance, 60% sporadic
FGFR2 gene
*bicoronal synostosis&raquo_space; brachycephaly
*normal extremities
*midface hypoplasia&raquo_space; proptosis, apparent micrognathia
*intracranial anomalous venous drainage, hydrocephalus
*early lamboid fusion&raquo_space; Chiari I malformation
*variant associated w/acanthosis nigricans

Question 1

Apert Syndrome

Answer 1

AD, incomplete penetrance, usually sporadic
FGFR2 gene
*symmetric complex syndactylies (usu digits 2-4)
*bicoronal synostosis&raquo_space; brachycephaly
metopic/sagittal sutures fuse late (~2-4yo)&raquo_space; hypertelorism
*ptosis, downward-sloping palpebral fissures
*proptosis, strabismus (v-shaped pattern)
*mid face hypoplasia&raquo_space; hypoplastic/stenotic choanae
often require trach
*cognitive defects
*excess sweating; worse acne in adolescence

Question 2

Pfeiffer Syndrome

Answer 2

Acrocephalosyndactyly
FGFR1/2
*broad thumbs/toes
thumbs deviate radially, toes deviate medially
*bicoronal synostosis (brachycephaly, acrocephaly, oxycephaly)
*midface hypoplasia, “beaked” nose

Question 3

DiGeorge

Answer 3

22q11 deletion > abnl 3rd/4th pharyngeal pouches
Thymic hypoplasia > T-cell immunodeficiency
Parathyroid hypoplasia > hypocalcemia
CHD: tetralogy of Fallot, pulmonary atresia, VSD
Cleft lip/palate
Abnl facies: hypertelorism, low-set ears, hypoplastic mandible, “upward bowing” of upper lip (perpetual smile)

Question 4

Noonan Syndrome

Answer 4

Down-slanting hypertelorism w/epicanthal folds
Deeply-grooved philtrum
Short webbed neck, low posterior hairline
Pectus carinatum/excavatum
Developmental delay
Cryptorchidism
Coarse/curly hair
Short stature, joint laxity
Triangular face, low post. rotated ears
Coagulation defects
Pulm Stenosis, HOCM
M:F 1:1

Question 5

Holt Oram Syndrome

Answer 5

ASD
UE Defects (3-jointed thumbs)

Question 6

Lesch Nyhan Syndrome

Answer 6

Self mutilation
Intellectual disability
Choreiform movements
High uric acid

Question 7

McCune Albright Syndrome

Answer 7

Cafe au lait spots
Precocious puberty
Abnl bones (fibrous dysplasia)

Question 8

Laurence-Moon-Biedl Syndrome

Answer 8

now split into Laurence-Moon and Bardet-Biedl syndromes

AR

progressive CNS, ophtho, endocrine dz
can look like Prader-Willi (obese, hypogonadism) but LMB more anomalies like syndactyly, retinal dystrophy

Question 9

Aicardi Syndrome

Answer 9

Seizures, absence of corpus callosum
Macrocephaly, ocular abnl

X-linked dominant

Question 10

Wiskott-Aldrich Syndrome

Answer 10

X-linked recessive WASP mutation
Immunodeficiency, TCP, eczema
Tx: abx, IVIg, s/t splenectomy, BMT

Question 11

Waardenburg Syndrome

Answer 11

AD
Hypopigmentation (iris, hair, skin)
Sensorineural hearing loss
Wide nasal bridge

Question 12

Rubinstein-Taybi Syndrome

Answer 12

Broad thumb

Cryptorchidism

Question 13

Russell Silver Syndrome

Answer 13

Triangular face

Growth retardation

Question 14

Prune Belly Syndrome

Answer 14

Lack of abdominal muscle&raquo_space;
bladder outlet obstruction&raquo_space; oligohydramnios&raquo_space;
pulmonary hypoplasia
also undescended testes

Question 15

Treacher Collins

Answer 15

Conductive hearing loss
Small jaw
Ear, lower eyelid abnl
NORMAL intelligence 
AD