Pituitary hormone deficiency

Gene: MAGEL2

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains AMBER. The additional comments from GLH's is "Usually manifests at birth with muscular hypotonia in all patients and distal joint contractures in a majority of affected individuals, therefore likely that these patients will be tested using alternative panel(s). Further clinical input needed to determine if this panel would be used for these patients."

Created: 31 Jan 2023, 3:01 p.m. | Last Modified: 31 Jan 2023, 4:42 p.m.

Panel Version: 2.106

Comment on list classification: Promoting to amber but with a recommendation for green rating following GMS review. More than 3 patients reported with plausible disease causing variants in MAGEL2 and a pituitary hormone deficiency

Created: 18 Sep 2022, 8:53 p.m. | Last Modified: 18 Sep 2022, 8:53 p.m.

Panel Version: 2.57

Associated with Schaaf-Yang syndrome #615547 (AD) in OMIM.

PMID: 31504653 - Gregory et al 2019 - report 4 patients from 3 unrelated families (2 White European, 1 White Chilean) with the same c.1996dup, p.Q666Pfs*47. variant in MAGEL2, who all presented with variable congenital hypopituitarism (CH) and arthrogryposis. In 2 cases it was found to be a de novo variant. In the other two it would found not to be maternally inherited but paternal DNA was not available.

PMID: 29359444 - Enya et al 2018 - report 3 patients from 2 Japanese families with Schaaf-Yang syndrome with arthrogryposis and endocrinological abnormalities. In both families variants in MAGEL2 were identified (c.1912C>T, p.Gln638*, inherited from the heterozygous father, and the de novo variant c.3131C>A, p.Ser1044*). The patient with the p.Ser1044* was diagnosed with panhypopituitarism.

PMID: 30323850 - Hidalgo-Santos et al 2018 - report a patient with Schaaf-Yang syndrome and a de novo variant in MAGEL2 (c.3019 C > T, p.Gln1007*). The patient presented with distal contractures, hypotonia, autism spectrum disorder, digestive abnormalities, partial hypopituitarism with central hypothyroidism and growth hormone (GH) deficiency

Created: 18 Sep 2022, 8:49 p.m. | Last Modified: 18 Sep 2022, 8:49 p.m.

Panel Version: 2.53

Review on behalf of Professor Mehul Dattani, UCL GOS Institute of Child Health/Great Ormond Street Hospital for Children. Gregory LC, Shah P, Sanner JRF, Arancibia M, Hurst J, Jones WD, Spoudeas H, Le Quesne Stabej P, Williams HJ, Ocaka LA, Loureiro C, Martinez-Aguayo A, Dattani MT.J Clin Endocrinol Metab. 2019 Dec 1;104(12):5737-5750. doi: 10.1210/jc.2019-00631.PMID:31504653

Created: 14 Sep 2022, 4:44 p.m. | Last Modified: 14 Sep 2022, 4:44 p.m.

Panel Version: 2.15

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)

Phenotypes
Schaaf-Yang syndrome, OMIM:615547

Publications

• 31504653
• 29359444
• 30323850