Pituitary hormone deficiency

Gene: EIF2S3

Comment on list classification: Promoting to Amber. 2 cases reported with hypopituitarism. In another case growth hormone deficiency is noted so adding the watchlist tag.

Created: 16 Sep 2022, 9:48 p.m. | Last Modified: 16 Sep 2022, 9:48 p.m.

Panel Version: 2.41

Comment on mode of inheritance: No female cases reported to date.

Created: 16 Sep 2022, 9:44 p.m. | Last Modified: 16 Sep 2022, 9:44 p.m.

Panel Version: 2.37

Associated with MEHMO syndrome in OMIM #300148 (XLR)

PMID: 30878599 - Gregory et al 2019 - X-chromosome exome sequencing identified a missense variant in EIF2S3 (p.Pro432Ser) in 3 related males with normal head circumferences and mild learning difficulties, hypopituitarism (GH and TSH deficiencies), and an unusual form of glucose dysregulation. The authors state this is the first time this combination of phenotypes has been reported in the literature.

Several other studies (PMID: 23063529,PMID: 27333055, PMID: 28055140) report the more severe MEHMO syndrome phenotype with severe learning difficulties, all in males. Heterozygous females are unaffected.
In PMID: 27333055 (Moortgat et al 2016) the growth hormone deficiency is noted in 2 related males, but for 1 it is reported that the pituitary gland and stalk were normal (not mentioned for the other). In PMID: 28055140 (Skopkova et al 2017) panhypopituitarism and partial hypopituitarism are noted as a clinical feature in two unrelated Slovakian patients (both with the same p.Ile465Serfs*4 variant).

Created: 16 Sep 2022, 9:44 p.m. | Last Modified: 16 Sep 2022, 9:44 p.m.

Panel Version: 2.35

Review on behalf of Professor Mehul Dattani, UCL GOS Institute of Child Health/Great Ormond Street Hospital for Children. Gregory LC, Ferreira CB, Young-Baird SK, Williams HJ, Harakalova M, van Haaften G, Rahman SA, Gaston-Massuet C, Kelberman D, GOSgene, Qasim W, Camper SA, Dever TE, Shah P, Robinson ICAF, Dattani MT.EBioMedicine. 2019 Apr;42:470-480. doi: 10.1016/j.ebiom.2019.03.013. Epub 2019 Mar 14.PMID:30878599

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

Panel Version: 2.15

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
HYPOPITUITARISM, GLUCOSE INTOLERANCE, FEATURES OF MEHMO SYNDROME; MEHMO syndrome, OMIM:300148

Publications

• 30878599