Key Features: Overgrowth, Rasopathies, Trinucleotide repeats

Question 1

KTW Syndrome

Answer 1

Port-wine stain, hemihypertrophy

Question 2

Proteus

Answer 2

Elephant man overgrowth, always due to same somatic mutation

Question 3

Simpson-Golabi-Behmel

Answer 3

Overgrowth, “Bulldog” syndrome

Question 4

Sotos

Answer 4

Sparse hair, pointed chin, overgrowth, flushed cheeks

Question 5

Weaver

Answer 5

Rapid continuous growth, coarse facies, hoarse cry as babies

Question 6

Cardiofaciocutaneous

Answer 6

Skin abnormalities, CHDs, craniofacial abnormalities

Question 7

Costello

Answer 7

ID, HCM/Pulmonic stenosis, rhabdomyosarcoma/neuroblastoma

Question 8

NF1

Answer 8

Lisch nodules, café au lait, neurofibromas, optic pathway glioma

Question 9

Legius

Answer 9

NF1 symptoms without Lisch nodules or neurofibromas

Question 10

Noonan

Answer 10

“Male turner syndrome” (outdated) but also occurs in females, webbed neck, pulmonic stenosis, short stature

Question 11

LEOPARD

Answer 11

Noonan + multiple liver spots/freckles

Question 12

Fragile X

Answer 12

Large ears, large testicles, most common form of inherited ID/autism, maternal anticipation, 5’UTR expansions

Question 13

Fragile X Premutation

Answer 13

Males – fragile x associated tremor/ataxia

Females – Primary ovarian insufficiency

Question 14

Friedrich’s Ataxia

Answer 14

Only AR repeat expansion, ataxia, cardiac concerns, intronic expansions

Question 15

Huntington’s

Answer 15

Chorea, psychomotor deterioration, paternal anticipation, exonic expansions

Question 16

Myotonic Dystrophy (DM)

Answer 16

Cataracts, balding, muscular dystrophy, maternal anticipation, 3’UTR repeats

Question 17

Congenital DM

Answer 17

More severe (more repeats), hypotonia, respiratory, ID, early death

Question 18

Spinal Bulbar Muscular Atrophy (Kennedy)

Answer 18

Allelic to androgen insensitivity, muscular atrophy with endocrine dysfunction, repeat expansion

Question 19

Spinocerebellar Ataxia

Answer 19

Ataxia, chorea, cerebellar atrophy, repeat expansion