Congenital hypothyroidism

Gene: SLC16A2

Green List (high evidence)

Groeneweg et al., 2025 (PMID: 40420837) describe 8 females with heterozygous SLC16A2 variants; 5 with missense variants, 1 frameshift, and 2 translocations, t(X;19) and t(X;20), that disrupt SLC16A2. Phenotypes included variable neurocognitive impairment, psychiatric/behavioural features, and an appropriate thyroid profile. Compared with asymptomatic carrier, and non-carrier female relatives, affected individuals had lower FT4, higher T3, and lower rT3. Both translocation cases appeared to be as severe as affected males. X-chromosome inactivation studies in patient fibroblasts showed skewed X-inactivation in all 7 evaluated individuals. Functional studies showed that missense variants markedly reduced MCT8-mediated thyroid hormone uptake in vitro, and MCT8-specific T3 uptake was reduced in fibroblasts from 5 of 7 tested patients. This adds to previously reported affected heterozygous females (Frints et al, 2008 PMID: 18398436; Quesada-Espinosa et al, 2021 PMID:34296368; Olivati et al, 2022 PMID: 35782622; Sriram et al, 2024 PMID:38345890).

Created: 29 Oct 2026, 2:11 p.m. | Last Modified: 29 Oct 2026, 2:11 p.m.

Panel Version: 4.1

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Allan-Herndon-Dudley syndrome

Publications

• (PMID: 40420837
• 18398436
• 34296368
• 35782622
• 38345890)

To expand the scope of the Congenital hypothyroidism panel, this gene was added and the version changed to 1.8. This gene and information originates from the Hyperthyroidism panel (Version 1.6, code 236). This addition was approved by the Genomics England Clinical Team.

Created: 19 Dec 2018, 1:21 p.m.

Added the 'treatable' tag to this gene, after feedback from Krish Chatterjee and Carla Moran, Institute of Metabolic Science, Cambridge; TRIAC (a thyroid hormone analogue) can be used as a treatment for Allan-Herndon Dudley syndrome due to defects in SLC16A2: comment imported from the Hyperthyroidism panel.

Created: 8 Aug 2018, 7:52 a.m.

Report variants in this gene as part of diagnostic practice : Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge (From expert review Krishna Chatterjee and Carla Moran)

Created: 15 Mar 2017, 4:49 p.m.

Comment when marking as ready: gene has been assessed for involvement in Resistance to thyroid hormone according to expert reviews and further curation

Created: 15 Mar 2017, 3:47 p.m.

Variants in this GENE are reported as part of current diagnostic practice