Background Chitayat-Hall syndrome, initially described in 1990, is a rare condition characterised by distal arthrogryposis, intellectual disability, dysmorphic features and hypopituitarism, in particular growth hormone deficiency. The genetic aetiology has not been identified.
Methods and results We identified three unrelated families with a total of six affected patients with the clinical manifestations of Chitayat-Hall syndrome. Through whole exome or whole genome sequencing, pathogenic variants in the MAGEL2 gene were identified in all affected patients. All disease-causing sequence variants detected are predicted to result in a truncated protein, including one complex variant that comprised a deletion and inversion.
Conclusions Chitayat-Hall syndrome is caused by pathogenic variants in MAGEL2 and shares a common aetiology with the recently described Schaaf-Yang syndrome. The phenotype of MAGEL2-related disorders is expanded to include growth hormone deficiency as an important and treatable complication.
- growth hormone deficiency
- schaaf-yang syndrome
- chitayat-hall syndrome
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JLM and DC contributed equally.
Contributors CC, SM, FR, NA, RR, MM, SA, MJMN, CLD, RW, PM and DC performed clinical assessment and provided phenotypic information regarding the patients. FR, FDL, JG, FFH, CN, J-FS, JLM, RJ, DJS, CRM, SWS, JO and SW provided sequencing, data analysis, interpretation and validation of variants. RJ, VL and MMA performed phasing experiments for the variant in family 3. The manuscript was drafted by RJ, FR, DC and JLM. All authors provided critical revision of the article.
Funding The McLaughlin Centre, University of Toronto, Toronto, Canada, and Fondation Jeanne et Jean- Louis Lévesque (JLM). The Centre for Genetic Medicine, The Hospital for Sick Children, Toronto, Canada. FDL has a fellowship funded by FCT - Fundação para a Ciência e a Tecnologia (SFRH/BD/84650/2010).
Competing interests None declared.
Patient consent Parental/guardian consent obtained.
Ethics approval The Hospital for Sick Children, Toronto, Canada, and Centre hospitalier universitaire Sainte-Justine.
Provenance and peer review Not commissioned; externally peer reviewed.