Human Genetics

, Volume 133, Issue 7, pp 847–859 | Cite as

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

  • Sara M. SarasuaEmail author
  • Luigi Boccuto
  • Julia L. Sharp
  • Alka Dwivedi
  • Chin-Fu Chen
  • Jonathan D. Rollins
  • R. Curtis Rogers
  • Katy Phelan
  • Barbara R. DuPont
Original Investigation


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.


Autism Spectrum Disorder Precocious Puberty Array Comparative Genomic Hybridization 22q13 Deletion Ring Chromosome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank the patients and families who participated in this study and made this work possible and the Phelan–McDermid Syndrome Foundation who organized the biannual family conferences where much of the data collection took place. We thank Gail Stapleton and Cindy Skinner who managed data collection at the family conferences. We thank Dr. Amy Lawton-Rauh and Dr. Charles Schwartz for helpful comments on the manuscript. We dedicate this paper to the memory of Julianne S. Collins.

This work was supported, in part, by a fellowship to SMS from the Phelan–McDermid Syndrome Foundation; the Genetics Endowment of South Carolina; and the South Carolina Department of Disabilities and Special Needs.

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

439_2014_1423_MOESM1_ESM.pdf (641 kb)
Supplementary material 1 (PDF 641 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Sara M. Sarasua
    • 1
    Email author
  • Luigi Boccuto
    • 1
  • Julia L. Sharp
    • 2
  • Alka Dwivedi
    • 1
  • Chin-Fu Chen
    • 1
  • Jonathan D. Rollins
    • 1
  • R. Curtis Rogers
    • 1
  • Katy Phelan
    • 3
  • Barbara R. DuPont
    • 1
  1. 1.Office of Bioinformatics and EpidemiologyGreenwood Genetic CenterGreenwoodUSA
  2. 2.Department of Mathematical SciencesClemson UniversityClemsonUSA
  3. 3.Hayward Genetics Center and Department of PediatricsTulane University School of MedicineNew OrleansUSA

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