Congenital hypothyroidism

Gene: SLC26A4

monogenic-polygenic tag added based on Nicholas et al., 2016 (PMID:27525530) who report triallelic (digenic) mutations in SLC26A4 and TPO (3 cases).

Created: 16 Feb 2017, 4:42 p.m.

Comment when marking as ready: Rated green plus >3 cases.

Created: 14 Feb 2017, 5:31 p.m.

Comment on list classification: Updated rating from Red to Green: 1 green review plus >3 unrelated cases of SLC26A4 causing Pendred syndrome (PDS, MIM:274600). Although the deafness phenotype of PDS may present first, Helen Brittain notes that phenotype variability is recognised and therefore including it on the panel for the minority of cases that may have a milder but progressive hearing component.

Created: 14 Feb 2017, 5:30 p.m.

Added 'treatable' tag based on Reviewer comment and PMID:21543982: Nutritional iodide intake is an important modifier of the thyroid phenotype in Pendred syndrome. With sufficient dietary iodide, about 90% of patients are clinically and biochemically euthyroid (normal thyroid function). In the remaining 10% with elevated TSH level, goiter is always present.

Created: 13 Feb 2017, 4:30 p.m.

PMID:17876604 (Banghova et al., 2008) note that hypothyroidism in Pendred syndrome can (albeit rarely) be present from birth. They investigated 197 Czech Caucasian children with CH detected by the neonatal screening in 1985-2005. They find 2 patients compound heterozygous for SLC26A4.

Created: 13 Feb 2017, 4:18 p.m.

Comment on mode of inheritance: Mode of inheritance confirmed by OMIM.

Created: 13 Feb 2017, 4:06 p.m.

Green List (high evidence)

Often euthyroid if iodine replete.

Created: 11 Feb 2017, 12:38 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Sensorineural deafness; enlarged vestibular aqueduct; Mondini defect; partial iodide organification defect; goitre; mild hypothyroidism

Publications

• PMID: 9398842
• PMID: 11932316