Chitayat-Hall and Schaaf-Yang syndromes:a common aetiology: expanding the phenotype of <i>MAGEL2</i>-related disorders

Jobling, Rebekah; Stavropoulos, Dimitri J.; Marshall, Christian R.; Cytrynbaum, Cheryl; Axford, Michelle M.; Londero, Vanessa; Moalem, Sharon; Orr, Jennifer; Rossignol, Francis; Lopes, Fátima; Gauthier, Julie; Alos, Nathalie; Rupps, Rosemarie; McKinnon, Margaret L.; Adam, Shelin; Nowaczyk, Małgorzata J.M.; Walker, Susan; Scherer, Stephen W.; Nassif, Christina; Hamdan, Fadi F.; Deal, Cheri; Soucy, Jean‐François; Weksberg, Rosanna; MacLeod, Patrick; Michaud, Jacques L.; Chitayat, David

doi:10.1136/jmedgenet-2017-105222

Cited by 31 publications

(35 citation statements)

References 17 publications

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“…Literature review yielded 23 articles and 1 Letter to the Editor pertaining to these syndromes, which are summarized in the Preferred Reporting Items for Systematic Reviews (PRISMA) diagram (Figure ) . We include a simplified summary of the patients' symptoms (Table ) and further summaries of all CHS and SYS patients to date (Table S1 in Appendix S1).…”

Section: Resultsmentioning

confidence: 99%

“…Because MAGEL2 is a single‐exon gene, frameshift mutations may not cause NMD, but instead a variety of truncated or elongated protein products. We hypothesize that this could also be driving the high degree of intrasyndrome variability and the observation of both dominant negative and less severe haploinsufficiency as mechanisms of disease . However, this is insufficient to explain all of the intrasyndrome variability, as even patients carrying the same mutation can have a high degree of variability in their presentations.…”

Section: Discussionmentioning

confidence: 99%

“…Its core symptoms have been reported as distal arthrogryposis, hypopituitarism, intellectual disability (ID), and facial dysmorphisms . In 2018, CHS was reported to arise from pathogenic variants in MAGEL2 …”

Section: Introductionmentioning

confidence: 99%

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MAGEL2‐related disorders: A study and case series

et al. 2019

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Pathogenic MAGEL2 variants result in the phenotypes of Chitayat‐Hall syndrome (CHS), Schaaf‐Yang syndrome (SYS) and Prader‐Willi syndrome (PWS). We present five patients with mutations in MAGEL2, including the first patient reported with a missense variant, adding to the limited literature. Further, we performed a systematic review of the CHS and SYS literature, assess the overlap between CHS, SYS and PWS, and analyze genotype‐phenotype correlations among them. We conclude that there is neither a clinical nor etiological difference between CHS and SYS, and propose that the two syndromes simply be referred to as MAGEL2‐related disorders.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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MAGEL2‐related disorders: A study and case series

et al. 2019

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“…CHS (MIM#208080) also known as SHFYNG (MIM#615547) syndrome is an inherited autosomal dominant multisystem disease with a variety of symptoms including intellectual disability, delayed psychomotoric development and neonatal hypotonia with poor suckling, feeding problems in infancy and behavioral anomalies . CHS/SHFYNG is caused by variants on the paternal MAGEL2 allele.…”

Section: Differential Diagnosticmentioning

confidence: 99%

Crisponi/cold‐induced sweating syndrome: Differential diagnosis, pathogenesis and treatment concepts

et al. 2019

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Crisponi/cold-induced sweating syndrome (CS/CISS) is an autosomal recessive disease characterized by hyperthermia, camptodactyly, feeding and respiratory difficulties often leading to sudden death in the neonatal period. The affected individuals who survived the first critical years of life, develop cold-induced sweating and scoliosis in early childhood. The disease is caused by variants in the CRLF1 or in the CLCF1

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“…Summary of the patients' features and of the American College of Medical Genetics and Genomics (ACMG) criteria satisfying the pathogenic nature of the identified variants in NALCN, MAGEL2 and SCN2A WES, whole exome sequencing as having Opitz-C syndrome (OTCS; MIM#211750),14 indicating that there is an overlap between OTCS and SHFYNG syndromes. In addition, MAGEL2 mutations were reported in individuals initially diagnosed as having Chitayat-Hall syndrome (MIM#208080) leading to the conclusion that Chitayat-Hall and SHFYNG syndromes are likely the same disorder 15. MAGEL2 is highly expressed in the hypothalamus and it is part of a multi-subunit protein complex consisting of MAGEL2, the TRIM27 E3 ubiquitin ligase, and the USP7 deubiquitinating enzyme.…”

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confidence: 99%

Exome sequencing in Crisponi/cold‐induced sweating syndrome–like individuals reveals unpredicted alternative diagnoses

et al. 2019

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Crisponi/cold‐induced sweating syndrome (CS/CISS) is a rare autosomal recessive disorder characterized by a complex phenotype (hyperthermia and feeding difficulties in the neonatal period, followed by scoliosis and paradoxical sweating induced by cold since early childhood) and a high neonatal lethality. CS/CISS is a genetically heterogeneous disorder caused by mutations in CRLF1 (CS/CISS1), CLCF1 (CS/CISS2) and KLHL7 (CS/CISS‐like). Here, a whole exome sequencing approach in individuals with CS/CISS‐like phenotype with unknown molecular defect revealed unpredicted alternative diagnoses. This approach identified putative pathogenic variations in NALCN, MAGEL2 and SCN2A. They were already found implicated in the pathogenesis of other syndromes, respectively the congenital contractures of the limbs and face, hypotonia, and developmental delay syndrome, the Schaaf‐Yang syndrome, and the early infantile epileptic encephalopathy‐11 syndrome. These results suggest a high neonatal phenotypic overlap among these disorders and will be very helpful for clinicians. Genetic analysis of these genes should be considered for those cases with a suspected CS/CISS during neonatal period who were tested as mutation negative in the known CS/CISS genes, because an expedited and corrected diagnosis can improve patient management and can provide a specific clinical follow‐up.

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Chitayat-Hall and Schaaf-Yang syndromes:a common aetiology: expanding the phenotype of MAGEL2-related disorders

Abstract: Chitayat-Hall syndrome is caused by pathogenic variants in and shares a common aetiology with the recently described Schaaf-Yang syndrome. The phenotype of-related disorders is expanded to include growth hormone deficiency as an important and treatable complication.

Cited by 31 publications

References 17 publications

MAGEL2‐related disorders: A study and case series

MAGEL2‐related disorders: A study and case series

Crisponi/cold‐induced sweating syndrome: Differential diagnosis, pathogenesis and treatment concepts

Exome sequencing in Crisponi/cold‐induced sweating syndrome–like individuals reveals unpredicted alternative diagnoses

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