Overgrowth syndromes

Question 1

Klippel-Trénaunay-Weber Syndrome (KTW Syndrome)

Answer 1

Inheritance: Sporadic, may be due to somatic changes in early development
Gene: Unknown
Major features:
●Port-wine stain
●Hypertrophy of bone and soft tissues, often in one limb
●Varicose veins
●Lymphatic malformations
●Vascular malformations

Question 2

Proteus Syndrome

Answer 2

Inheritance: N/A
Gene: Due to SOMATIC MOSAIC AKT1 mutation c.49G>A in all cases
Major features:
●Overgrowth of skin, bones, muscles, fatty tisues, blood vessels, and lymphatic vessels
●Overgrowth is non-congenital and disproportionate
●Cerebriform connective tissue nevi

Possibly what “the Elephant Man” had

Question 3

Simpson-Golabi-Behmel Syndrome

Answer 3

Inheritance: X-linked recessive
Genes: GPC3, CXORF5
Major features:
●Macrosomia
●Macroglossia
●Macrocephaly
●Mild-to-severe intellectual disability
●Coarse facial features
●Diastasis recti
●Congenital heart defects
●Diaphragmatic hernia
●Genitourniary anomalies
●Gi anomalies
●Polydactyly
●Pectus deformities
●Scoliosis
●Vertebral fusion
●Rib anomalies
Sometimes referred to as “Bulldog Syndrome” (outdated terminology, but may be helpful for remember phenotypic features, unfortunately)

Question 4

Sotos Syndrome

Answer 4

Inheritance: Autosomal dominant, 95% de novo
Gene: NSD1
Major features:
●Height and/or head circumference 2+ standard deviations from the mean
●Macrocephaly
●Mild-to-severe intellectual disability
●Flushed cheeks
●Monotone voice with stuttering
●Developmental delay
●Cardiac anomalies
●Behavioral problems
●Flat feet
●Joint hyperlaxity
●Renal anomalies
●Scoliosis
●Seizures
●Advanced bone age
●Maternal preeclampsia

Question 5

Weaver Syndrome

Answer 5

Inheritance: Autosomal dominant
Gene: EZH2
Major features:
●Tall stature
●Rapid, continuous growth
●Intellect can range from normal to severe intellectual disability
●Macrocephaly
●Coarse facial features
●Advanced bone age
●Poor coordination
●Soft, doughy skin
●Camptodactyly
●Umbilical hernia
●Hoarse, low cry in infancy

Question 6

Characteristic facial features of Sotos syndrome

Answer 6

Characteristic facial appearance
oBroad, prominent forehead
oDolicocephaly
oSparse frontotemporal hair
oDownslanting palpebral fissures
oMalar flushing
oBitemporal narrowing
oPointed chin