Clinical and genomic evaluation of 201 patients with Phelan-McDermid syndrome

Hum Genet. 2014 Jul;133(7):847-59. doi: 10.1007/s00439-014-1423-7. Epub 2014 Jan 31.


This study is the first to describe age-related changes in a large cohort of patients with Phelan-McDermid syndrome (PMS), also known as 22q13 deletion syndrome. Over a follow-up period of up to 12 years, physical examinations and structured interviews were conducted for 201 individuals diagnosed with PMS, 120 patients had a focused, high-resolution 22q12q13 array CGH, and 92 patients' deletions were assessed for parent-of-origin. 22q13 genomic anomalies include terminal deletions of 22q13 (89 %), terminal deletions and interstitial duplications (9 %), and interstitial deletions (2 %). Considering different age groups, in older patients, behavioral problems tended to subside, developmental abilities improved, and some features such as large or fleshy hands, full or puffy eyelids, hypotonia, lax ligaments, and hyperextensible joints were less frequent. However, the proportion reporting an autism spectrum disorder, seizures, and cellulitis, or presenting with lymphedema or abnormal reflexes increased with age. Some neurologic and dysmorphic features such as speech and developmental delay and macrocephaly correlated with deletion size. Deletion sizes in more recently diagnosed patients tend to be smaller than those diagnosed a decade earlier. Seventy-three percent of de novo deletions were of paternal origin. Seizures were reported three times more often among patients with a de novo deletion of the maternal rather than paternal chromosome 22. This analysis improves the understanding of the clinical presentation and natural history of PMS and can serve as a reference for the prevalence of clinical features in the syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Chromosome Deletion*
  • Chromosome Disorders / genetics*
  • Chromosomes, Human, Pair 22 / genetics*
  • Cohort Studies
  • Comparative Genomic Hybridization
  • Developmental Disabilities / genetics
  • Female
  • Humans
  • Infant
  • Logistic Models
  • Male
  • Middle Aged
  • Young Adult

Supplementary concepts

  • Telomeric 22q13 Monosomy Syndrome