Description
Resistance to thyroid hormone inclusion criteria (41920)
Resistance to thyroid hormone defined biochemically as elevated levels of T3 and/or T4 with non-suppressed TSH levels

Resistance to thyroid hormone exclusion criteria (41920)
A high likelihood that the phenotype is completely explained by an acquired aetiology (eg drugs, assay interference, iodine deficiency, TSH-secreting pituitary tumour).
A pathogenic mutation in a known causative gene which completely explains the phenotype.

Prior genetic testing guidance (41920)
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition. 
- Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.  

PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.

Resistance to thyroid hormone prior genetic testing genes (41920)
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice: 
Elevated T3, low/normal T4 and/or clinical features suggestive of Allan-Herndon-Dudley syndrome: SLC16A2 (MCT8)
Elevated T3, low/normal T4, and/or clinical features suggestive of RTHalpha: THRA
Raised T4, normal/low T3, high reverse T3, low plasma selenium: SECISBP2, TRU-TCA1-1 (TRNAU1)

Closing statement (41920)
These requirements will be kept under continual review during the main programme and may be subject to change.

1 reviewer

  • Louise Daugherty (Genomics England Curator)

    Group: Other
    Workplace: Other

5 genes

5 reviewed, 4 green

List Gene Reviews Mode of inheritance Details
5 genes
Green Green List (high evidence)
SECISBP2
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • Other
  • Radboud University Medical Center, Nijmegen
  • Literature
Phenotypes
  • Abnormal thyroid hormone metabolism
  • Selenocysteine insertion sequence binding protein 2 (SBP2) defect
  • Thyroid hormone metabolism, abnormal, 609698
  • THYROID HORMONE METABOLISM, ABNORMAL
  • Short stature-delayed bone age due to thyroid hormone metabolism deficiency
Green Green List (high evidence)
SLC16A2
1 review
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • Other
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Literature
Phenotypes
  • Monocarboxylate transporter 8 (MCT8) defect
  • Allan-Herndon-Dudley syndrome
  • Allan_Herndon_Dudley Syndrome
  • AHDS
  • 300523
  • Allan-Herndon-Dudley syndrome, 300523
  • Allan-Herndon-Dudley Syndrome
  • ALLAN-HERNDON-DUDLEY SYNDROME
  • ALLAN-HERNDON SYNDROME
  • MONOCARBOXYLATE TRANSPORTER 8 DEFICIENCY
  • TRIIODOTHYRONINE RESISTANCE
  • T3 RESISTANCE
  • MENTAL RETARDATION, X-LINKED, WITH HYPOTONIA
  • MENTAL RETARDATION AND MUSCULAR ATROPHY
  • mental retardation, X-linked, with hypotonia
  • MCT8 (SLC16A2)-specific thyroid hormone cell transporter deficiency
  • monocarboxylate transporter 8 (MCT8) deficiency
Green Green List (high evidence)
THRA
1 review
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Eligibility statement prior genetic testing
  • Other
  • Radboud University Medical Center, Nijmegen
  • Literature
  • Expert Review Green
Phenotypes
  • RTH alpha
  • congenital nongoitrous hypothyroidism 6
  • Resistance to thyroid hormone alpha
  • Resistance to Thyroid Hormone due to defective thyroid receptor alpha (RTHa)
  • Hypothyroidism, congenital, nongoitrous, 6, 614450
  • HYPOTHYROIDISM, CONGENITAL, NONGOITROUS, 6
  • CHNG6
Green Green List (high evidence)
THRB
1 review
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • Other
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Literature
Phenotypes
  • Resistance to thyroid hormone (RTH)
  • thyroid hormone unresponsiveness, generalized RTH, RTH beta
  • Refetoff syndrome
  • Thyroid Hormone Resistance, Selective Pituitary
  • PRTH
  • 145650
  • Thyroid hormone resistance, 188570
  • Thyroid hormone resistance, autosomal recessive, 274300
  • Thyroid hormone resistance, selective pituitary, 145650
  • Thyroid Hormone Resistance (monoallelic)
  • THYROID HORMONE RESISTANCE, GENERALIZED, AUTOSOMAL DOMINANT
  • GRTH
  • THYROID HORMONE UNRESPONSIVENESS HYPERTHYROXINEMIA, FAMILIAL EUTHYROID, SECONDARY TO PITUITARY AND PERIPHERAL RESISTANCE TO THYROID HORMONES
  • THYROID HORMONE RESISTANCE, GENERALIZED, AUTOSOMAL RECESSIVE
  • THYROID HORMONE UNRESPONSIVENESS
  • REFETOFF SYNDROME
  • THYROID HORMONE RESISTANCE, SELECTIVE PITUITARY
  • HYPERTHYROIDISM, FAMILIAL, DUE TO INAPPROPRIATE THYROTROPIN SECRETION
Red Red List (low evidence)
TRU-TCA1-1
1 review
1 red
Unknown
Sources
  • Eligibility statement prior genetic testing
  • Expert list
  • Expert Review Red
Tags
  • locus-type-rna-transfer

0 STRs

0 reviewed, 0 green

List STR Reviews Mode of inheritance Details
0 STRss

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