1. Panels
  2. Congenital hypothyroidism

Congenital hypothyroidism (Version 0.43)

Level 3: Thyroid disorders
Level 2: Endocrine disorders

Relevant disorders: Hypothyroidism HP:0000821
Panel types: Victorian Clinical Genetics Services, Genetic Health Queensland, Rare Disease
Description
This panel contains genes associated with congenital hypothyroidism

With thanks to Genomics England PanelApp for the original design of this panel.
Panel Activity

2 reviewers

  • Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

  • Chirag Patel (Genetic Health Queensland)

40 Entities

22 reviewed, 34 green

List Entity Reviews Mode of inheritance Details
40 Entitiess
Green List (high evidence)
CDCA8
1 review
1 green 		BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Congenital hypothyroidism, MONDO:0018612, CDCA8-related
Tags
Green List (high evidence)
DUOX2
1 review
1 green 		BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Thyroid dyshormonogenesis 6, 607200
Tags
  • treatable
Green List (high evidence)
DUOXA2
1 review
1 green 		BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Thyroid dyshormonogenesis 5, 274900
Tags
Green List (high evidence)
FOXE1
1 review
1 green 		BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Bamforth Lazarus syndrome, MIM#241850 (hypothyroidism)
  • Hypothyroidism, Thyroidal Or Athyroidal, With Spiky Hair And Cleft Palate, 241850
Tags
Green List (high evidence)
GLIS3
1 review
1 green 		BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Diabetes mellitus, neonatal, with congenital hypothyroidism, MIM# 610199
Tags
Green List (high evidence)
GNAS
1 review
1 green 		MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Pseudohypoparathyroidism Ia, MIM#103580 (Hypothyroidism)
Tags
Green List (high evidence)
HESX1
1 review
1 green 		BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Pituitary hormone deficiency, combined, 5, MIM# 182230
Tags
Green List (high evidence)
IGSF1
1 review
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
  • Genomics England PanelApp
Phenotypes
  • Hypothyroidism, central, and testicular enlargement, MIM# 300888
Tags
Green List (high evidence)
IRS4
1 review
1 green 		X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Hypothyroidism, congenital, nongoitrous, 9, MIM# 301035
Tags
Green List (high evidence)
IYD
0 reviews
 BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • childhood/adolescent onset hypothyroidism
  • Thyroid dyshormonogenesis 4, 274800
  • normal iodide organification
  • Congenital hypothyroidism
  • raised urinary MIT and DIT
  • goitre
Tags
Green List (high evidence)
KMT2D
1 review
1 green 		MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review
  • Expert Review Green
Phenotypes
  • Branchial arch abnormalities, choanal atresia, athelia, hearing loss, and hypothyroidism syndrome (BCAHH), MIM#620186
Tags
Green List (high evidence)
LHX3
0 reviews
 BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Pituitary hormone deficiency, combined, 3, 221750
  • sensorineural deafness
  • GH, TSH, LH, FSH, PRL deficiency
  • limited neck rotation
  • short cervical spine
  • anterior pituitary may be normal, hypoplastic or enlarged
Tags
  • treatable
Green List (high evidence)
LHX4
0 reviews
 MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • anterior pituitary hypoplasia
  • GH, TSH, ACTH, variable gonadotrophin deficiencies
  • etopic posterior pituitary
  • Pituitary hormone deficiency, combined, 4, 262700
  • cerebellar abnormalities
Tags
  • treatable
Green List (high evidence)
NKX2-1
0 reviews
 MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Choreoathetosis And Congenital Hypothyroidism With Or Without Pulmonary Dysfunction, 610978
Tags
Green List (high evidence)
NKX2-5
1 review
1 green 		MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Hypothyroidism, congenital nongoitrous, 5, 225250
  • thyrioid ectopy, thyroid agenesis, congenital heart disease
Tags
Green List (high evidence)
OTX2
1 review
1 green 		MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Pituitary hormone deficiency, combined, 6, MIM# 613986
Tags
Green List (high evidence)
PAX8
1 review
1 green 		MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Hypothyroidism, Congenital, Nongoitrous, 2, 218700
  • thyroid dysgenesis
  • Congenital hypothyroidism
  • thyroid hypoplasia
  • Hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia, 218700
  • eutopic gland-in-situ
  • urogenital tract malformations
Tags
Green List (high evidence)
POU1F1
0 reviews
 BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • congenital hypothyroidism
  • Pituitary hormone deficiency, combined, 1, 613038 (Hypopthyroidism)
Tags
Green List (high evidence)
PRKAR1A
0 reviews
 MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Acrodysostosis, mild hormone resistance (TSH, PTH, GPCR-cAMP signalling hormones
  • Acrodysostosis 1, with or without hormone resistance, 101800
Tags
Green List (high evidence)
PROP1
0 reviews
 BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • 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
  • 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
  • Pituitary hormone deficiency, combined, 2, 262600
Tags
Green List (high evidence)
SECISBP2
1 review
1 green 		BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Thyroid hormone metabolism, abnormal, MIM# 609698
Tags
Green List (high evidence)
SLC16A2
0 reviews
 X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Allan-Herndon-Dudley syndrome, MIM# 300523
Tags
Green List (high evidence)
SLC26A4
0 reviews
 BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • enlarged vestibular aqueduct
  • Sensorineural deafness
  • partial iodide organification defect
  • mild hypothyroidism
  • Pendred syndrome, 274600 (congenital deafness and thyroid goitre)
  • goitre
  • Mondini defect
Tags
Green List (high evidence)
SLC26A7
1 review
1 green 		BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Congenital hypothyroidism, MONDO:0018612, SLC26A7-related
Tags
Green List (high evidence)
SLC5A5
0 reviews
 BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Apparent athyreosis on nuclear medicine scan
  • childhood onset hypothyroidism
  • goitre
  • Thyroid dyshormonogenesis 1, 274400
  • HYPOTHYROIDISM, CONGENITAL, DUE TO DYSHORMONOGENESIS, 1
Tags
Green List (high evidence)
TBL1X
0 reviews
 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
  • Genomics England PanelApp
Phenotypes
  • isolated mild-moderate central hypothyroidism
  • Hypothyroidism, congenital, nongoitrous, 8, 301033
Tags
Green List (high evidence)
TG
0 reviews
 BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Congenital hypothyroidism
  • Thyroid dyshormonogenesis 3, 274700
  • TDH3
  • low thyroglobulin, goitre
Tags
Green List (high evidence)
THRA
0 reviews
 MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Congenital hypothyroidism or thyroid agenesis
  • delayed dentition
  • macrocephaly
  • Hypothyroidism, Congenital, Nongoitrous, 6, 614450
  • Hypothyroidism, congenital, nongoitrous, 6, 614450
  • neurodevelopmental delay
  • Resistance to thyroid hormone
  • constipation
  • skeletal dysplasia
  • growth retardation
  • macrocytic anaemia
Tags
Green List (high evidence)
THRB
0 reviews
 BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • HYPERTHYROIDISM, FAMILIAL, DUE TO INAPPROPRIATE THYROTROPIN SECRETION
  • THYROID HORMONE RESISTANCE, GENERALIZED, AUTOSOMAL RECESSIVE
  • THYROID HORMONE RESISTANCE, GENERALIZED, AUTOSOMAL DOMINANT
  • Thyroid hormone resistance, autosomal recessive, 274300
  • Thyroid Hormone Resistance, Selective Pituitary
  • Resistance to thyroid hormone (RTH)
  • 145650
  • PRTH
  • REFETOFF SYNDROME
  • THYROID HORMONE RESISTANCE, SELECTIVE PITUITARY
  • thyroid hormone unresponsiveness, generalized RTH, RTH beta
  • Thyroid Hormone Resistance (monoallelic)
  • Thyroid hormone resistance, 188570
  • Thyroid hormone resistance, selective pituitary, 145650
  • THYROID HORMONE UNRESPONSIVENESS
  • THYROID HORMONE UNRESPONSIVENESS HYPERTHYROXINEMIA, FAMILIAL EUTHYROID, SECONDARY TO PITUITARY AND PERIPHERAL RESISTANCE TO THYROID HORMONES
  • Refetoff syndrome
  • GRTH
Tags
Green List (high evidence)
TPO
0 reviews
 BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Congenital hypothyroidism
  • Iodide organification defect
  • goitre
  • TDH2A
  • Thyroid dyshormonogenesis 2A, 274500
Tags
Green List (high evidence)
TRHR
1 review
1 green 		BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Hypothyroidism, congenital, nongoitrous, 7, MIM# 618573
Tags
Green List (high evidence)
TSHB
0 reviews
 BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Congenital hypothyroidism
  • Hypothryoidism, congenital, nongoitrous 4, 275100
  • severe isolated central hypothyroidism
Tags
Green List (high evidence)
TSHR
0 reviews
 BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Hypothyroidism, congenital, nongoitrous, 1 275200
  • thyroid dysgenesis
  • Congenital hypothyroidism
  • thyroid hypoplasia
  • compensated hypothryoidism
  • subclinical hypothyroidism
  • Hypothyroidism, Congenital, Nongoitrous, 1, 275200
  • eutopic gland-in-situ
  • TSH resistance
Tags
Green List (high evidence)
TUBB1
2 reviews
1 green 		BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Genomics England PanelApp
Phenotypes
  • Macrothrombocytopenia, autosomal dominant, TUBB1-related, OMIM # 613112
  • Primary congenital hypothyroidism, thyroid dysgenesis, macroplatelets
Tags
Amber List (moderate evidence)
DUOX1
1 review
 BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • congenital hypothyroidism, No OMIM #
Tags
Amber List (moderate evidence)
DUOXA1
1 review
 BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • congenital hypothyroidism, No OMIM #
Tags
Amber List (moderate evidence)
GATA6
1 review
 MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Pancreatic agenesis and congenital heart defects, OMIM# 600001
Tags
Amber List (moderate evidence)
TTF1
2 reviews
 MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • congenital hypothyroidism, thyroid dysgenesis, No OMIM #
Tags
Red List (low evidence)
SOX3
0 reviews
 X-LINKED: hemizygous mutation in males, biallelic mutations in females
Sources
  • Expert Review Red
  • Genomics England PanelApp
Phenotypes
  • Panhypopituitarism, X-linked, MONDO:0010712
  • Panhypopituitarism, X-linked, OMIM:312000
  • Intellectual disability, X-linked, with panhypopituitarism, MONDO:0010252
  • Mental retardation, X-linked, with isolated growth hormone deficiency, OMIM:300123
Tags
Red List (low evidence)
TTF2
1 review
1 red 		MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
  • Literature
Phenotypes
  • congenital hypothyroidism, thyroid dysgenesis, No OMIM #
Tags

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