IllnessThyroid dyshormonogenesis, differential diagnosis

NGS +

In 10-15% of cases with congenital hypothyroidism, the thyroid gland is normal in size or enlarged, but the thyroid hormones are reduced or absent due to dyshormonogenesis. Congenital hypothyroidism is often accompanied by only mild symptoms and is therefore not recognized at first, but if left untreated, it can lead to slow growth, metabolic disorders and intellectual deficits. Dyshormonogenesis results from mutations in one of several genes for enzymes involved in the production of thyroid hormones, resulting in low hormone levels. Since mutations in the TSHB (main cause of central hypothyroidism) and TSHR genes can prevent the synthesis of thyroid hormones, they should be considered for differential diagnosis. The inheritance of enzymatic dyshormonogenesis is usually autosomal recessive, but individual cases also suggest dominant inheritance with incomplete penetrance. The diagnostic yield is largely unknown. Therefore, an inconspicuous genetic finding does not mean a reliable exclusion of a suspected clinical diagnosis.

(Basic diagnostic genes: ###; additional genes: ###)

Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312914/

• Alias: Familial thyroid dyshormonogenesis
• Alias: Hypothyroidism, congenital, dyshormonogenesis
• Alias: Iodine accumulation, transport or trapping defect
• Alias: Thyroid dyshormonogenesis
• Allelic: ACTH-independent macronodular adrenal hyperplasia (GNAS)
• Allelic: Autoimmune thyroid disease, susceptibility to, 3 (TG)
• Allelic: Chorea, hereditary benign (NKX2-1)
• Allelic: Deafness, AR 4, with enlarged vestibular aqueduct (SLC26A4)
• Allelic: Growth hormone deficiency with pituitary anomalies (HESX1)
• Allelic: Hyperthyroidism, familial gestational (TSHR)
• Allelic: McCune-Albright syndrome, somatic, mosaic (GNAS)
• Allelic: Microphthalmia, syndromic 5 (OTX2)
• Allelic: Osseous heteroplasia, progressive (GNAS)
• Allelic: Pseudohypoparathyroidism Ia, Ib, Ic (GNAS)
• Allelic: Pseudopseudohypoparathyroidism (GNAS)
• Allelic: Septooptic dysplasia (HESX1)
• Allelic: Thyroid cancer, nonmedullary, 1 (NKX2-1)
• Allelic: Thyroid cancer, nonmedullary, 4 (FOXE1)
• Allelic: Thyroid carcinoma with thyrotoxicosis (TSHR)
• Allan-Herndon-Dudley syndrome: T3 resistance; MR, XL, + hypotonia (SLC16A2)
• Bamforth-Lazarus syndrome: [a]thyroidal hypothyroidism, spiky hair, cleft palate (FOXE1)
• Choreoathetosis, hypothyroidism + neonatal respiratory distress (NKX2-1)
• Diabetes mellitus, neonatal, with congenital hypothyroidism (GLIS3)
• Hyperthyroidism, nonautoimmune (TSHR)
• Hypothyroidism, central, + testicular enlargement (IGSF1)
• Hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia (PAX8)
• Hypothyroidism, congenital, nongoitrous 1 (TSHR)
• Hypothyroidism, congenital, nongoitrous 4 (TSHB)
• Hypothyroidism, congenital, nongoitrous 8 (TBL1X)
• Hypothyroidism, congenital, nongoitrous 9 (IRS4)
• Pendred syndrome (SLC26A4)
• 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, hypothyroidism (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)