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Interdisciplinary CompetenceMolecular Diagnostics
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IllnessHypothyroidism, congenital; differential diagnosis

Summary

Short information

Comprehensive differential diagnostic panel for congenital Hypothyroidism comprising 41 guideline-curated and alltogether 46 curated genes

ID
HP3377
Number of genes
33 Accredited laboratory test
Examined sequence length
34,8 kb (Core-/Core-canditate-Genes)
61,1 kb (Extended panel: incl. additional genes)
Analysis Duration
on request
Material
  • EDTA-anticoagulated blood (3-5 ml)
Diagnostic indications

NGS +

 

Gene panel

Selected genes

NameExon Length (bp)OMIM-GHeredity
DUOX24647AR
DUOXA2963AR
FOXE11122AR
GLIS32328AR
GNAS1185AD
IYD870AR
NKX2-11206AD
NKX2-5975AD
PAX81353AD
SLC26A42343AR
SLC26A72047AR
SLC5A51932AR
TG8307AR
TPO2802AD, AR
TSHB417AR
TSHR2295AD, AR
CDCA8853AD, AR
HESX1558AD, AR
IGSF14026XLR
IRS43774XLR
LHX31209AR
LHX41173AD
OTX2870AD
POU1F1876AD, AR
PRKAR1A1146AD, AR
PROP1681AR
SECISBP22565AR
SLC16A21620XL
TBL1X1734XL
THRA1233AR
THRB1386AR
TRHR1197AR
TUBB11356AD

Informations about the disease

Clinical Comment

Congenital hypothyroidism (CH) is caused by partial or complete loss of thyroid function. It occurs in infants postnatally due to reduced thyroid hormone levels. In up to 85% of CH cases, the thyroid gland is absent, hypoplastic or abnormally localized. In the remaining cases, a normal sized gland or enlarged goiter is present, but thyroid hormones are reduced or absent (dyshormonogenesis). Less commonly, fewer thyroid hormones are produced due to impaired stimulation of the pituitary gland. CH-affected infants are less active, have feeding difficulties and constipation. If left untreated, CH can lead to intellectual deficits, delayed growth and impaired metabolism. However, if treatment begins in the first two weeks after birth, infants usually develop normally. The most common forms of syndromal CH include Pendred and Bamforth-Lazarus syndromes as well as brain-pulmonary-thyroid syndrome. The most common cause of CH worldwide is iodine deficiency in the diet of the mother and affected infant. Genetic causes account for about 15-20% of CH cases. The cause of the most common genetic form of CH, thyroid dysgenesis, is usually unknown or mainly caused by mutated PAX8 and TSHR genes in 2-5% of inherited cases. Thyroid dyshormonogenesis is caused by mutations in the DUOX2, SLC5A5, TPO or TG genes. Mutations in the TSHB gene interfere with thyroid hormone synthesis. All classical inheritance patterns are observed in CH. Despite the many CH genes already known, no causative mutations are identified in most CH cases.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK185066/

https://www.ncbi.nlm.nih.gov/books/NBK1467/

https://pubmed.ncbi.nlm.nih.gov/33272083/

 

Synonyms
  • Alias: Konnatale Hypothyreose
  • Alias: Primäre angeborene Hypothyreose
  • Allelic: ACTH-independent macronodular adrenal hyperplasia (GNAS)
  • Allelic: Adrenocortical tumor, somatic (PRKAR1A)
  • Allelic: Atrial septal defect 7, with/-out AV conduction defects (NKX2-5)
  • Allelic: Autoimmune thyroid disease, susceptibility to, 3 (TG)
  • Allelic: Carney complex, type 1 (PRKAR1A)
  • Allelic: Chorea, hereditary benign (NKX2.1)
  • Allelic: Conotruncal heart malformations, variable (NKX2-5)
  • Allelic: Deafness, AR 4, with enlarged vestibular aqueduct (SLC26A4)
  • Allelic: Growth hormone deficiency with pituitary anomalies (HESX1)
  • Allelic: Hyperthyroidism, familial gestational (TSHR)
  • Allelic: Hyperthyroidism, nonautoimmune (TSHR)
  • Allelic: Hypoplastic left heart syndrome 2 (NKX2-5)
  • Allelic: Macrothrombocytopenia, autosomal dominant, TUBB1-related (TUBB1)
  • Allelic: McCune-Albright syndrome, somatic, mosaic (GNAS)
  • Allelic: Microphthalmia, syndromic 5 (OTX2)
  • Allelic: Myxoma, intracardiac (PRKAR1A)
  • Allelic: Osseous heteroplasia, progressive (GNAS)
  • Allelic: Pigmented nodular adrenocortical disease, primary, 1 (PRKAR1A)
  • Allelic: Pituitary adenoma 3, multiple types, somatic (GNAS)
  • Allelic: Pseudohypoparathyroidism Ia, Ib, Ic (GNAS)
  • Allelic: Pseudopseudohypoparathyroidism (GNAS)
  • Allelic: Septooptic dysplasia (HESX1)
  • Allelic: Tetralogy of Fallot (NKX2-5)
  • Allelic: Thyroid adenoma, hyperfunctioning, somatic (TSHR)
  • Allelic: Thyroid cancer, nonmedullary, 1 (NKX2-1)
  • Allelic: Thyroid cancer, nonmedullary, 4 (FOXE1)
  • Allelic: Thyroid carcinoma with thyrotoxicosis (TSHR)
  • Allelic: Ventricular septal defect 3 (NKX2-5)
  • Acrodysostosis 1, with/-out hormone resistance (PRKAR1A)
  • Allan-Herndon-Dudley syndrome (SLC16A2)
  • Bamforth-Lazarus syndrome (FOXE1)
  • Choreoathetosis, hypothyroidism, neonatal respiratory distress (NKX2-1)
  • Congenital hypothyroidism; thyroid dysgenesis [panelapp] (CDCA8)
  • Diabetes mellitus, neonatal, with congenital hypothyroidism (GLIS3)
  • Hypogonadotropic hypogonadism 6 with/-out anosmia (FGF8)
  • Hypothyroidism, central, testicular enlargement (IGSF1)
  • Hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia (PAX8)
  • Hypothyroidism, congenital, nongoitrous, 1 (TSHR)
  • Hypothyroidism, congenital, nongoitrous, 2 (PAX8)
  • Hypothyroidism, congenital, nongoitrous, 4 (TSHB)
  • Hypothyroidism, congenital, nongoitrous, 5 (NKX2-5)
  • Hypothyroidism, congenital, nongoitrous, 6 (THRA)
  • Hypothyroidism, congenital, nongoitrous, 7 (TRHR)
  • Hypothyroidism, congenital, nongoitrous, 8 (TBL1X)
  • Hypothyroidism, congenital, nongoitrous, 9 (IRS4)
  • Pendred syndrome (SLC26A4)
  • Pituitary hormone deficiency, combined, 1 (POU1F1)
  • Pituitary hormone deficiency, combined, 2 (PROP1)
  • Pituitary hormone deficiency, combined, 3 Pituitary hormone deficiency, combined, 3 (LHX3)
  • Pituitary hormone deficiency, combined, 4 (LHX4)
  • Pituitary hormone deficiency, combined, 5 (HESX1)
  • Pituitary hormone deficiency, combined, 6 (OTX2)
  • Primary congenital hypothyroidism; dyshormonogenesis [panelapp} (SLC26A7)
  • Pseudohypoparathyroidism Ia (GNAS)
  • Retinal dystrophy, early-onset, with/-out pituitary dysfunction (OTX2)
  • Thyroid dyshormonogenesis 1 (SLC5A5)
  • Thyroid dyshormonogenesis 2A (TPO)
  • Thyroid dyshormonogenesis 3 (TG)
  • Thyroid dyshormonogenesis 4 (IYD)
  • Thyroid dyshormonogenesis 5 (DUOXA2)
  • Thyroid dyshormonogenesis 6 (DUOX2)
  • Thyroid hormone metabolism, abnormal (SECISBP2)
  • Thyroid hormone resistance (THRB)
  • Thyroid hormone resistance, AR (THRB)
  • Thyroid hormone resistance, selective pituitary (THRB)
Heredity, heredity patterns etc.
  • AD
  • AR
  • XL
  • XLR
OMIM-Ps
  • Multiple OMIM-Ps
ICD10 Code
E03.8

Bioinformatics and clinical interpretation

No text defined