Fountain et al. (2017) reported 18 patients with SHFYNG ascertained on the basis of genetic studies from several different research groups or laboratories. Joint contractures were present in almost all patients, and ranged from only the interphalangeal joints to lethal fetal akinesia with severe arthrogryposis. All patients had heterozygous truncating mutations in the MAGEL2 gene.
Mejlachowicz et al (2015) reported two unrelated families with lethal AMC and heterozygous truncating frameshift MAGEL2 mutations on paternal allele.
In 4 unrelated boys with a syndrome resembling Prader-Willi syndrome, Schaaf et al. (2013) identified 4 different de novo heterozygous truncating mutations in the MAGEL2 gene with features resembling Prader-Willi syndrome; two patients had contractures of the proximal and distal interphalangeal joints.
Created: 27 Nov 2019, 12:21 p.m. | Last Modified: 27 Nov 2019, 12:21 p.m.
Panel Version: 2.84
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)
Schaaf-Yang syndrome; Prader-Willi-Like syndrome
G2P phenotype is 'ARTHROGRYPOSIS MULTIPLEX CONGENITA' with 'probable' disease confidence, in addition to 'Schaaf-Yang syndrome' with confirmed confidence. G2P rating based on PMID:26365340 who report 2 families with lethal arthrogryposis in deceased fetuses and MAGEL2 variant. PMID:27195816 (Fountain et al., 2017) identified the same heterozygous c.1996delC variant in 2 fetal siblings with Shaaf-Yang syndrome manifesting as AMC. PMID:31504653 (Gregory et al., 2019) report 5 patients (4 families), 3 of whom had arthrogryposis and the Gln666SerfsTer36 MAGEL2 variant. Additional papers reporting arthrogryposis as part of Schaaf-Yang syndrome E.g. PMID:29359444 so likely to be the same condition with variable severity/phenotype. Sufficient cases of arthrogryposis in the literature for a Green rating on Arthrogryposis panel.
Created: 26 Nov 2019, 3:21 p.m. | Last Modified: 26 Nov 2019, 3:21 p.m.
Panel Version: 2.65
Added to Arthrogryposis panel after agreement with Zerin Hyder (Genomics England Clinical Team), based on Arthrogryposis phenotye and Green rating on DDG2P panel V1.154.
Created: 26 Nov 2019, 3:16 p.m. | Last Modified: 26 Nov 2019, 3:16 p.m.
Panel Version: 2.64
Phenotypes for gene: MAGEL2 were changed from Schaaf-Yang syndrome, 615547; ARTHROGRYPOSIS MULTIPLEX CONGENITA to Schaaf-Yang syndrome, 615547; ARTHROGRYPOSIS MULTIPLEX CONGENITA; Prader-Willi-Like syndrome
Publications for gene: MAGEL2 were set to 26365340; 27195816; 31504653; 29359444
Publications for gene: MAGEL2 were set to
gene: MAGEL2 was added gene: MAGEL2 was added to Arthrogryposis. Sources: Literature,Other,Expert Review Green Mode of inheritance for gene: MAGEL2 was set to MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed) Phenotypes for gene: MAGEL2 were set to Schaaf-Yang syndrome, 615547; ARTHROGRYPOSIS MULTIPLEX CONGENITA