Overgrowth

Question 1

[Gen/Overgrowth/BWS]

Characteristics of Beckwith-Wiedemann syndrome (6)

Answer 1

1. Growth disorder (neonatal hypoglycemia, macrosomia, macroglossia, hemihyperplasia)
2. Omphalocele
3. Embryonal tumors (Wilms tumor, hepatoblastoma, neuroblastoma, rhabdomyosarcoma)
4. Visceromegaly, adrenocortical cytomegaly
5. Renal abnormalities (medullary dysplasia, nephrocalcinosis, medullary sponge kidney, and nephromegaly)
6. Ear creases/pits

Question 2

[Gen/Overgrowth/Sotos]

Cardinal symptoms of Sotos syndrome? (3)

Answer 2

1. Facial appearance: broad and prominent forehead with a dolichocephalic head shape, sparse frontotemporal hair, downslanting palpebral fissures, malar flushing, long and narrow face, long chin
2. Learning disability: early developmental delay, mild-to-severe intellectual impairment
3. Overgrowth: height and/or head circumference ≥2 SD above the mean):born LGA and rapid growth for initial 5 years

Question 3

[Gen/Overgrowth/Sotos]

Diagnosis?

1. Neuro: Cranial MRI/CT abnormalities, seizures, behavioral problems (most notably autistic spectrum disorder)
2. Cardiac anomalies
3. Renal anomalies
4. MSK: Joint hyperlaxity, advanced bone age, pes planus, scoliosis
5. Maternal preeclampsia, neonatal complications

Answer 3

Sotos syndrome

Question 4

[Gen/Overgrowth/Sotos]

Sotos syndrome

Most common inheritance pattern?
Genetic cause?

Answer 4

Autosomal dominant
NSD1

Question 5

[Gen/Overgrowth/BWS]

Most common genetic cause and percentage of Beckwith-Wiedemann syndrome? (2)

Answer 5

1. Loss of methylation on the maternal chromosome at imprinting center 2 (IC2) in 50% of affected individuals
2. Paternal uniparental disomy for chromosome 11p15 in 20%

Question 6

[Gen/Overgrowth/Proteus]

Diagnosis?

1. Progressive segmental overgrowth (the skeleton, skin, adipose, and central nervous systems), progresses rapidly in the toddler, severe disfigurement
2. Tumors (lipomas, lymphagiomata, hemangiomata)
3. Pulmonary complications
4. Deep vein thrombosis and pulmonary embolism

Answer 6

Proteus syndrome

Question 7

[Gen/Overgrowth/Proteus]

Genetic cause of Proteus syndrome?

Answer 7

Somatic mosaicism AKT1 c.49G>A (p.Glu17Lys)

Question 8

[Gen/Overgrowth/BWS]

Embryonal tumor associated with Beckwith-Wiedemann syndrome? (4)

Answer 8

1. Wilms tumor
2. Hepatoblastoma
3. Neuroblastoma
4. Rhabdomyosarcoma

Question 9

[Derm/Vascular]

Diagnosis?

Vascular malformation in lower limbs
Limb overgrowth

Answer 9

Klippel-Trenaunay syndrome