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A newborn presents with a prominent glabella, hypertelorism, microcephaly, and hypotonia. She has seizures in the first week of life. A microarray reveals a deletion at 4p16.3.

  • Deletion: 4p16.3 (variable size)
  • Critical genes: NSD2 (formerly WHSC1), NELFCD (formerly WHSC2), LETM1 (seizure phenotype)
  • ~85-90% de novo; ~10-15% inherited (parental translocation)
  • Facial features: prominent glabella (forehead ridge between eyebrows), hypertelorism (wide-set eyes), high forehead → creates "Greek warrior helmet" appearance
  • Microcephaly, intellectual disability (usually severe)
  • Seizures (~90%)
  • Growth restriction
  • Congenital heart defects, cleft lip/palate
  • CMA or FISH for 4p16.3
  • Parental karyotypes are indicated to detect a balanced translocation, which accounts for ~10-15% of cases
  • Supportive and multidisciplinary; no targeted therapy
  • Seizure control with anti-seizure medications; seizures often improve with age
  • Feeding support (frequently gastrostomy) for poor feeding and reflux; monitor growth
  • Early intervention: physical, occupational, and speech therapy; developmental support
  • Surveillance and management of associated cardiac, renal, ophthalmologic, and skeletal (scoliosis) anomalies

Cat = 5p, Wolf = 4p. Two terminal short-arm deletion syndromes paired by mnemonic. "Wolf" has 4 letters (Wolf-Hirschhorn = 4p deletion). A cat has 5 fingers per paw (Cri du chat = 5p deletion).

Cat-wolf mnemonic for the 5p and 4p terminal deletions
Cat-wolf mnemonic for the 5p and 4p terminal deletions

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