Congenital hypothyroidism
Gene: SLC26A4monogenic-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.
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
22 February 2017: Promoted to Version 1. Reviews were assessed, and panel was revised according to expert review and additional curation. After discussion with the reviewer and in-house clinicians, it was agreed to include the genes for 'combined pituitary hormone deficiency' (CPHD) on the panel, since patients can present with central hypothyroidism (CH). In these cases, CH does not occur in isolation, but is one of the evolving pituitary hormone deficiencies.
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
Phenotypes for SLC26A4 were set to Pendred syndrome, 274600 (congenital deafness and thyroid goitre); Sensorineural deafness; enlarged vestibular aqueduct; Mondini defect; partial iodide organification defect; goitre; mild hypothyroidism
Mode of inheritance for SLC26A4 was changed to BIALLELIC, autosomal or pseudoautosomal
Mode of inheritance for SLC26A4 was changed to BIALLELIC, autosomal or pseudoautosomal
Publications for SLC26A4 were set to 9398842; 11932316
Phenotypes for SLC26A4 were set to Pendred syndrome, 274600 (diffuse thyroid enlargement (goiter)); Sensorineural deafness; enlarged vestibular aqueduct; Mondini defect; partial iodide organification defect; goitre; mild hypothyroidism
SLC26A4 was added to Congenital hypothyroidism or thyroid agenesispanel. Source: Eligibility statement prior genetic testing
SLC26A4 was added to Congenital hypothyroidism or thyroid agenesispanel. Sources: Other
SLC26A4 was created by rfoulger