Expansion of the phenotypic and mutational spectrum of Carpenter syndrome

Rabab Khairat*, Rasha Elhossini, Nara Sobreira, Elizabeth Wohler, Ghada Otaify, Amal M. Mohamed, Ehab R. Abdel Raouf, Inas Sayed, Mona Aglan, Samira Ismail, Samia A. Temtamy

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


Carpenter syndrome 1 (CRPT1) is an acrocephalopolysyndactyly (ACPS) disorder characterized by craniosynostosis, polysyndactyly, obesity, and other malformations. It is caused by mutations in the gene RAB23. We are reporting on two patients from two unrelated consanguineous Egyptian families. Patient 1 presented with an atypical clinical presentation of Carpenter syndrome including overgrowth with advanced bone age, epileptogenic changes on electroencephalogram and autistic features. Patient 2 presented with typical clinical features suggestive of Carpenter syndrome. Therefore, Patient 1 was subjected to whole exome sequencing (WES) to find an explanation for his unusual features and Patient 2 was subjected to Sanger sequencing of the coding exons of theRAB23 gene to confirm the diagnosis. We identified a novel homozygous missense RAB23 variant (NM_001278668:c.T416C:p.Leu139Pro) in Patient 1 and a novel homozygous splicing variant (NM_016277.5:c.398+1G > A) in Patient 2. We suggest that the overgrowth with advanced bone age, electroencephalogram epileptogenic changes, and autistic features seen in Patient 1 are an expansion of the Carpenter phenotype and could be due to the novel missense RAB23 variant. Additionally, the novel identified RAB23 variants in Patient 1 and 2 broaden the spectrum of variants associated with Carpenter syndrome.

Original languageEnglish
Article number104377
JournalEuropean Journal of Medical Genetics
Issue number1
Publication statusPublished - Jan 2022
Externally publishedYes


  • Acrocephalopolysyndactyly
  • Carpenter syndrome 1
  • RAB23
  • WES

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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