Congenital hypothyroidism

Gene: LHX4

Comment on list classification: Updated rating from Grey to Green: 1 Green review (from gene submitter). Plus >3 cases of LHX4 mutations causing combined pituitary hormone deficiency, which can present with CH. Confirmed DD-G2P gene. At least 1 case mentions hypothyroidism specifically (PMID:25955177).

Created: 21 Feb 2017, 10:33 a.m.

LHX4 is an early pituitary transcription factor. Mutations in early or late pituitary transcription factors may cause central hypothyroidism (CH), a particular hypothyroid condition due to an insufficient stimulation by TSH of an otherwise normal thyroid gland. In these cases, CH does not occur in isolation, but is one of the evolving pituitary hormone deficiencies [PMID:26416826].

Created: 21 Feb 2017, 10:29 a.m.

>3 cases of LHX4 mutations causing Pituitary hormone deficiency, combined, 4 (MIM:262700).

Created: 20 Feb 2017, 11:16 a.m.

Confirmed DD-G2P gene for LHX4-related combined pituitary hormone deficiency.

Created: 20 Feb 2017, 11:10 a.m.

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
GH, TSH, ACTH, variable gonadotrophin deficiencies, cerebellar abnormalities, anterior pituitary hypoplasia, etopic posterior pituitary

Publications

• Syndromic short stature in patients with a germline mutation in the LIM homeobox LHX4. Machinis K, Pantel J, Netchine I, Léger J, Camand OJ, Sobrier ML, Dastot-Le Moal F, Duquesnoy P, Abitbol M, Czernichow P, Amselem S. Am J Hum Genet. 2001 Nov
• 69(5):961-8.