IllnessHypothyroidism, congenital; differential diagnosis

NGS +

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/

• 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)