Overgrowth Syndromes

Question 1

Cowden syndrome

Answer 1

• PTEN, SDHB, SDHD, KLLN; AD
• PTEN is tumor suppressor
• Similar to Bannayan-Riley-Ruvalcaba syndromeand Proteus syndrome, sometimes together referred to as “PTEN hamartoma tumor syndrome”
• Overgrowth syndrome
• Signs:
  
  • Macrocephaly: “PTEN BIG HEAD”
  • Hamartomas (nearly 100% chance)
  • Derm signs (e.g., trichilemmomas, pic)
  • Sometimes: Lhermitte-Duclos (rare, noncancerous brain tumor), ID/DD
• Increased cancer risk (%):
  
  • Breast: 50-85
  • Thyroid: 30-40
  • Uterine: 25-30
  • CRC: 5-10
  • Kidney: 30-35
  • Melanoma: 6

Question 2

Weaver syndrome

Answer 2

• EZH2; AD
• Overgrowth syndrome
• Tall stature, sometimes macrocephaly, mild ID, broad forehead, hypertelorism, joint contractures, hypo/hypertonia
• Increased risk for neuroblastoma in early childhood (exact % unknown)

Question 3

Beckwidth-Wiedmann syndrome

Answer 3

• Abn methylation at 11p15.5 imprinting centers (IGF2, CDKN1C, &more); 85% de novo due to imprinting, 15% AD due to point mutations
• Most cases caused by paternal UPD
• Overgrowth syndrome
• Signs:
  
  • Macroglossia
  • Macrosomia
  • Hemihypertrophy
  • Omphalocele
  • Hypoglycemia
  • Wilm’s tumor
• Increased cancer risk in childhood (before age 10):
  
  • 5-10% overall
  • Embryonal tumors:
    
    • Wilm’s tumor (40% of cases)
    • Hepatoblastoma
    • Neuroblastoma
    • Rhabdomyosarcoma
  • Adrenocortical tumor (20% of cases)