Description
This panel is used for clinical indication 'R145 Congenital hypothyroidism', and can also be applied as a virtual panel in the analysis of genome or exome data in the NHS Genomic Medicine Service.

Further information on the testing criteria and any overlapping clinical indications can be found within (https://www.england.nhs.uk/publication/national-genomic-test-directories/)  under 'R145 Congenital hypothyroidism'.

The content of this panel is overseen by NHS Genomic Medicine Service governance. In addition to the evidence for a gene:disease association, this requires consideration of technical aspects of the assay(s) available.

CNVs, STRs and genes encoded by the mitochondrial genome may not be routinely included in the analysis where the panel is NOT delivered by WGS. Please contact your Genomic Laboratory Hub for information regarding specific queries.

This panel was originally developed for the 100,000 Genomes Project and is still being used for participants in the project. For the rare disease eligibility criteria refer to: https://www.genomicsengland.co.uk/rarediseasecriteria100K

19th Dec 2018: additional Green genes from the Hyperthyroidism gene panel (Version 1.6, code 1.6) were added to this panel: SECISBP2, SLC16A2, THRB.



The content of this panel (version 2.0: https://panelapp.genomicsengland.co.uk/api/v1/panels/31/?version=2.0) was signed off under NHS Genomic Medicine Service governance on (31/07/2019).

This panel will continue to be curated. New changes will be reflected in an increase to the minor version of the panel and details of these can be viewed in the 'Panel Activity' page. Periodically, these changes will be reviewed by a NHS Genomic Medicine Service evaluation process for the GMS panels.

6 reviewers

  • Ellen McDonagh (Genomics England Curator)

    Group: other
    Workplace: other

  • Rebecca Foulger (Genomics England curator)

    Group: Other
    Workplace: Other

  • Louise Daugherty (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Nadia Schoenmakers (University of Cambridge)

    Group: GeCIP domain
    Workplace: Research lab

  • Ivone Leong (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Martina Owens (Exeter Genetics Laboratory, Royal Devon and Exeter NHS Foundation Trust)

    Group: NHS Genomic Medicine Centre
    Workplace: NHS diagnostic lab

36 Entities

36 reviewed, 30 green

List Entity Reviews Mode of inheritance Details
36 Entitiess
Green Green List (high evidence)
DUOX2
2 reviews
1 green
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • UKGTN
Phenotypes
  • Congenital hypothyroidism
  • Thryoid dyshormonogenesis 6, 607200
  • permanent congenital hypothyroidism
  • transient congenital hypothyroidism
  • eutopic gland-in-situ
  • goitre
  • borderline congenital hypothyroidism
  • iodide organification defect
Tags
  • monogenic-polygenic
Green Green List (high evidence)
DUOXA2
2 reviews
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Thyroid dyshormonogenesis 5, 274900
  • HYPOTHYROIDISM, CONGENITAL, DUE TO DYSHORMONOGENESIS, 5
  • eutopic gland-in-situ
  • mild congenital hypothyroidism
  • transient congenital hypothyroidism
Tags
  • deletions
  • monogenic-polygenic
Green Green List (high evidence)
FOXE1
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Emory Genetics Laboratory
  • Expert Review Green
  • UKGTN
Phenotypes
  • congenital hypothyroidism
  • Bamforth Lazarus syndrome, 241850 (hypothyroidism)
  • Hypothyroidism, Thyroidal Or Athyroidal, With Spiky Hair And Cleft Palate, 241850
  • thyroid agenesis
  • cleft palate
  • spiky hair
  • choanal atresia
Tags
Green Green List (high evidence)
GLIS3
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Congenital hypothyroidism
  • Diabetes mellitus, neonatal, with congenital hypothyroidism, 610199
  • neonatal non-autoimmune diabetes mellitus
  • severe congenital hypothyroidism
  • variable cholestasis
  • hepatic fibrosis
  • congenital glaucoma
  • polycystic kidneys
  • dysmorphic facies
  • sensorineural deafness
Tags
Green Green List (high evidence)
GNAS
1 review
MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
Phenotypes
  • Pseudohypoparathyroidism Ia, 103580 (Hypothyroidism)
Tags
Green Green List (high evidence)
HESX1
2 reviews
1 green
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Panhypopiuitarism
  • GH and evolving TSH, ACTH, LH/FSH deficiency
  • septo-optic dysplasia
  • anterior pituitary, ectopic posterior pituitary
  • agenesis of corpus callous
  • optic nerve hypoplasia
  • Pituitary hormone deficiency, combined, 5, 182230
Tags
Green Green List (high evidence)
IGSF1
2 reviews
1 green
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • central hypothyroidism
  • hypoprolactinaemia
  • GH deficiency
  • macroorchidism
  • Hypothyroidism, central, and testicular enlargement, 300888
Tags
Green Green List (high evidence)
IRS4
2 reviews
1 green
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • East of England GLH
  • Expert Review Green
Phenotypes
  • Congenital central hypothyroidism
Tags
Green Green List (high evidence)
IYD
2 reviews
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Other
Phenotypes
  • Congenital hypothyroidism
  • Thyroid dyshormonogenesis 4, 274800
  • goitre
  • childhood/adolescent onset hypothyroidism
  • normal iodide organification
  • raised urinary MIT and DIT
Tags
Green Green List (high evidence)
LHX3
2 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • GH, TSH, LH, FSH, PRL deficiency
  • limited neck rotation
  • short cervical spine
  • sensorineural deafness
  • anterior pituitary may be normal, hypoplastic or enlarged
  • Pituitary hormone deficiency, combined, 3, 221750
Tags
Green Green List (high evidence)
LHX4
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • GH, TSH, ACTH, variable gonadotrophin deficiencies
  • cerebellar abnormalities
  • anterior pituitary hypoplasia
  • etopic posterior pituitary
  • Pituitary hormone deficiency, combined, 4, 262700
Tags
Green Green List (high evidence)
NKX2-1
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Other
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Congenital hypothyroidism
  • Choreoathetosis, hypothyroidism, and neonatal respiratory distress, 610978
  • Choreoathetosis And Congenital Hypothyroidism With Or Without Pulmonary Dysfunction, 610978
  • CAHTP
  • Neurological abnormalities
  • benign hereditary chorea
  • neonatal respiratory distress syndrome
  • recurrent respiratory infections
Tags
Green Green List (high evidence)
OTX2
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • GH, TSH, ACTH, LH, FSH deficiency
  • Anophthalmia Retinal dystrophy
  • normal or hypoplastic anterior pituitary
  • ectopic posterior pituitary
  • Pituitary hormone deficiency, combined, 6, 613986
Tags
  • missense
Green Green List (high evidence)
PAX8
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Emory Genetics Laboratory
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Congenital hypothyroidism
  • Hypothyroidism, Congenital, Nongoitrous, 2, 218700
  • Hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia, 218700
  • urogenital tract malformations
  • thyroid hypoplasia
  • thyroid dysgenesis
  • eutopic gland-in-situ
Tags
Green Green List (high evidence)
POU1F1
2 reviews
1 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Pituitary hormone deficiency, combined, 1, 613038 (Hypopthyroidism)
  • congenital hypothyroidism
Tags
Green Green List (high evidence)
PRKAR1A
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • Acrodysostosis, mild hormone resistance (TSH, PTH, GPCR-cAMP signalling hormones
  • Acrodysostosis 1, with or without hormone resistance, 101800
Tags
Green Green List (high evidence)
PROP1
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • GH, TSH, LH, FSH, PRL deficiency with variable age of onset, evolving ACTH deficiency
  • Commonest cause of combined pituitary hormone deficit without extra pituitary manifestations
  • Hypoplastic or normal anterior pituitary although there have been reports of an enlarged anterior pituitary at initial scanning in childhood with spontaneous involution over time
  • Pituitary hormone deficiency, combined, 2, 262600
Tags
Green Green List (high evidence)
SECISBP2
2 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
Phenotypes
  • Short stature-delayed bone age due to thyroid hormone metabolism deficiency
  • Selenocysteine insertion sequence binding protein 2 (SBP2) defect
  • Abnormal thyroid hormone metabolism
  • Thyroid hormone metabolism, abnormal, 609698
  • THYROID HORMONE METABOLISM, ABNORMAL
Tags
Green Green List (high evidence)
SLC16A2
2 reviews
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Green
Phenotypes
  • MENTAL RETARDATION AND MUSCULAR ATROPHY
  • MCT8 (SLC16A2)-specific thyroid hormone cell transporter deficiency
  • monocarboxylate transporter 8 (MCT8) deficiency
  • ALLAN-HERNDON SYNDROME
  • Monocarboxylate transporter 8 (MCT8) defect
  • Allan-Herndon-Dudley syndrome
  • AHDS
  • MENTAL RETARDATION, X-LINKED, WITH HYPOTONIA
  • Allan_Herndon_Dudley Syndrome
  • mental retardation, X-linked, with hypotonia
  • MONOCARBOXYLATE TRANSPORTER 8 DEFICIENCY
  • Allan-Herndon-Dudley Syndrome
  • T3 RESISTANCE
  • TRIIODOTHYRONINE RESISTANCE
  • 300523
  • Allan-Herndon-Dudley syndrome, 300523
  • ALLAN-HERNDON-DUDLEY SYNDROME
Tags
  • treatable
Green Green List (high evidence)
SLC26A4
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • Other
Phenotypes
  • Pendred syndrome, 274600 (congenital deafness and thyroid goitre)
  • Sensorineural deafness
  • enlarged vestibular aqueduct
  • Mondini defect
  • partial iodide organification defect
  • goitre
  • mild hypothyroidism
Tags
  • monogenic-polygenic
  • treatable
Green Green List (high evidence)
SLC26A7
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • East of England GLH
  • Expert Review Green
Phenotypes
  • Primary congenital hypothyroidism (dyshormonogenesis)
Tags
Green Green List (high evidence)
SLC5A5
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Thyroid dyshormonogenesis 1, 274400
  • HYPOTHYROIDISM, CONGENITAL, DUE TO DYSHORMONOGENESIS, 1
  • Apparent athyreosis on nuclear medicine scan
  • goitre
  • childhood onset hypothyroidism
Tags
Green Green List (high evidence)
TBL1X
4 reviews
2 green
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • isolated mild-moderate central hypothyroidism
Tags
  • missense
Green Green List (high evidence)
TG
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • UKGTN
Phenotypes
  • Congenital hypothyroidism
  • Thyroid dyshormonogenesis 3, 274700
  • TDH3
  • low thyroglobulin, goitre
Tags
  • monogenic-polygenic
Green Green List (high evidence)
THRA
4 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Congenital hypothyroidism or thyroid agenesis
  • Hypothyroidism, Congenital, Nongoitrous, 6, 614450
  • Hypothyroidism, congenital, nongoitrous, 6, 614450
  • Resistance to thyroid hormone
  • skeletal dysplasia
  • growth retardation
  • macrocephaly
  • neurodevelopmental delay
  • constipation
  • delayed dentition
  • macrocytic anaemia
Tags
  • treatable
Green Green List (high evidence)
THRB
2 reviews
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
Phenotypes
  • Resistance to thyroid hormone (RTH)
  • THYROID HORMONE UNRESPONSIVENESS
  • 145650
  • REFETOFF SYNDROME
  • PRTH
  • Thyroid hormone resistance, autosomal recessive, 274300
  • Refetoff syndrome
  • THYROID HORMONE RESISTANCE, SELECTIVE PITUITARY
  • thyroid hormone unresponsiveness, generalized RTH, RTH beta
  • Thyroid hormone resistance, 188570
  • THYROID HORMONE RESISTANCE, GENERALIZED, AUTOSOMAL DOMINANT
  • THYROID HORMONE RESISTANCE, GENERALIZED, AUTOSOMAL RECESSIVE
  • Thyroid Hormone Resistance (monoallelic)
  • Thyroid hormone resistance, selective pituitary, 145650
  • HYPERTHYROIDISM, FAMILIAL, DUE TO INAPPROPRIATE THYROTROPIN SECRETION
  • GRTH
  • Thyroid Hormone Resistance, Selective Pituitary
  • THYROID HORMONE UNRESPONSIVENESS HYPERTHYROXINEMIA, FAMILIAL EUTHYROID, SECONDARY TO PITUITARY AND PERIPHERAL RESISTANCE TO THYROID HORMONES
Tags
  • treatable
Green Green List (high evidence)
TPO
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • UKGTN
Phenotypes
  • Congenital hypothyroidism
  • Thyroid dyshormonogenesis 2A, 274500
  • TDH2A
  • Iodide organification defect
  • goitre
Tags
  • monogenic-polygenic
Green Green List (high evidence)
TRHR
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • mild-moderate isolated central hypothyroidism
  • absent TSH and prolactin response to TRH
  • Thyrotropin-releasing hormone resistance, generalized
Tags
Green Green List (high evidence)
TSHB
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Other
Phenotypes
  • Congenital hypothyroidism
  • Hypothryoidism, congenital, nongoitrous 4, 275100
  • severe isolated central hypothyroidism
Tags
Green Green List (high evidence)
TSHR
2 reviews
1 green
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Congenital hypothyroidism
  • Hypothyroidism, Congenital, Nongoitrous, 1, 275200
  • Hypothyroidism, congenital, nongoitrous, 1 275200
  • TSH resistance
  • thyroid hypoplasia
  • subclinical hypothyroidism
  • thyroid dysgenesis
  • eutopic gland-in-situ
  • compensated hypothryoidism
Tags
Amber Amber List (moderate evidence)
CDCA8
2 reviews
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review
  • Expert Review Amber
  • Literature
  • NHS GMS
Phenotypes
  • Congenital hypothyroidism
  • thyroid dysgenesis
  • No OMIM number
Tags
Amber Amber List (moderate evidence)
15q11q13 recurrent (PWS/AS) region (BP1-BP3, Class 1) Loss
ISCA-37404-Loss
Region
1 review
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • ClinGen
  • Expert Review Amber
Phenotypes
  • microcephaly
  • 105834
  • Developmental delay, muscle weakness
  • Mental retardation
  • Angelman syndrome
  • 176270
  • Prader-Willi syndrome
Tags
Amber Amber List (moderate evidence)
15q11q13 recurrent (PWS/AS) region (BP2-BP3, Class 2) Loss
ISCA-37478-Loss
Region
1 review
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • ClinGen
  • Expert Review Amber
Phenotypes
  • microcephaly
  • Developmental delay, muscle weakness
  • Mental retardation
  • Angelman syndrome
  • 176270
  • Prader-Willi syndrome
  • 105830
Tags
Amber Amber List (moderate evidence)
NKX2-5
2 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • Other
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Hypothyroidism, congenital nongoitrous, 5, 225250
  • thyrioid ectopy, thyroid agenesis, congenital heart disease
Tags
Amber Amber List (moderate evidence)
TUBB1
2 reviews
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • East of England GLH
  • Expert Review Amber
Phenotypes
  • Primary congenital hypothyroidism, thyroid dysgenesis, macroplatelets
Tags
Red Red List (low evidence)
SOX3
2 reviews
1 green
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Red
  • Literature
Phenotypes
  • GH,TSH, ACTH, LH, FSH deficiency, variable mental retardation, undescended posterior pituitary, anterior pituitary hypoplasia, or persistence of the craniopharyngeal canal
Tags

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