OVERGROWTH SYNDROMES

Question 1

SOTOS SYN

Answer 1

Overgrowth in childhood, large head, Distinctive facial features: long, narrow face, small-pointed chin, reddened cheeks, montone voice, Genetics: NSD1 (histone methyltransferase»enzymes that modify histones), sporadic/de novo

Question 2

PROTEUS SYN

Answer 2

Affected bones grow out of proportion of rest of body (limbs, skull, spine), *cerebriform connective tissue nevus (thick, raised deeply grooved lesion), increased risk for DVT&raquo_space; pulmonary embolism, Genetics: mosaic mutation in AKT1

Question 3

SIMPSON-GOLABI-BEHMEL SYN

Answer 3

Large everything (weight, head, mouth, tongue), ID, risk for embryonal tumors (Wilms, hepatoblastoma, hepatcellular carcinoma, etc)–AFP serum levels and renal u/s for screening, square face, broad/distinctive hands; Genetics: GPC3 gene, X-linked recessive, females may show sx given skewed x-inactivation; NGS (panel given large overlap w/ other overgrowth syn)

Question 4

KLIPPEL-TRENAUNAY SYN

Answer 4

Port-wine stain, overgrowth of soft tissues and bones, vein malformations»DVTs and pulmonary embolisms, Genetics: PIK3CA gene&raquo_space; mutations make enzyme P13K over active&raquo_space; increased cell proliferation; Sporadic (somatic mutations!)

Question 5

WEAVER SYN

Answer 5

Tall stature, soft doughy skin, camptodactyly, increased risk for neuroblastoma, Genetics: EZH2 gene, A dominant