IllnessThyroid hormone receptor deficiency, differential diagnosis

NGS +

[Sanger]

Congenital hypothyroidism is a loss of thyroid function with either lower hormone levels or, in rare cases, resistance to these hormones. In up to 85% of cases the thyroid gland is absent, i.e. there is thyroid dysgenesis. In the remaining cases, thyroid hormones or their effect(s) are missing. Thyroid dyshormonogenesis and central (or pituitary) hypothyroidism also lead to congenital hypothyroidism due to a lack of thyroid hormone function. Affected babies are asymptomatic or less active and sleep more, have feeding problems and suffer from constipation. If left untreated, congenital, non-goitous hypothyroidism can lead to mental retardation and slow growth. Thyroid hormone resistance can be inherited autosomal dominantly, recessively or X-linked, each with variable expressivity. The diagnostic yield is largely unknown, as it depends in particular on the clinical findings.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK26373/

• Alias: Refetoff syndrome
• Alias: Resistance to thyroid hormone beta
• Alias: Resistance to thyroid hormone due to mutation in thyroid hormone receptor beta
• Alias: Thyroid hormone receptor deficiency, beta
• Allelic: AD hyperinsul., hypopituit., craniofacial/endoderm-derived abnorm. [panelapp] (FOXA2)
• Allelic: Adrenocortical tumor, somatic (PRKAR1A)
• Allelic: Amyloidosis, hereditary, transthyretin-related (TTR)
• Allelic: Analbuminemia (ALB)
• Allelic: Carney complex, type 1 (PRKAR1A)
• Allelic: Carpal tunnel syndrome, familial (TTR)
• Allelic: Congenital hyperinsulinism [panelapp] (FOXA2)
• Allelic: Hyperthyroidism, familial gestational (TSHR)
• Allelic: Hyperthyroidism, nonautoimmune (TSHR)
• Allelic: Intellectual developmental disorder, XL, with isolated growth hormone deficiency (SOX3)
• Allelic: Jackson-Weiss syndrome (FGFR1)
• Allelic: Myxoma, intracardiac (PRKAR1A)
• Allelic: Osteoglophonic dysplasia (FGFR1)
• Allelic: Pfeiffer syndrome (FGFR1)
• Allelic: Pigmented nodular adrenocortical disease, primary, 1 (PRKAR1A)
• Allelic: Thyroid adenoma, hyperfunctioning, somatic (TSHR)
• Allelic: Thyroid carcinoma with thyrotoxicosis (TSHR)
• Allelic: Trigonocephaly 1 (FGFR1)
• Acrodysostosis 1, with or without hormone resistance (PRKAR1A)
• Allan-Herndon-Dudley syndrome (SLC16A2)
• CHARGE syndrome (CHD7)
• Congenital hypopituitarism [panelapp] (FOXA2)
• Dysalbuminemic hyperthyroxinemia (ALB)
• Dysalbuminemic hypertriiodothyroninemia (ALB)
• Dystransthyretinemic hyperthyroxinemia (TTR)
• Growth hormone deficiency with pituitary anomalies (HESX1)
• Hartsfield syndrome (FGFR1)
• Hypogonadotropic hypogonadism 2 with/-out anosmia (FGFR1)
• Hypogonadotropic hypogonadism 3 with/-out anosmia (PROKR2)
• Hypogonadotropic hypogonadism 5 with/-out anosmia (CHD7)
• Hypogonadotropic hypogonadism 6 with/-out anosmia (FGF8)
• Hypothyroidism, central + testicular enlargement (IGSF1)
• Hypothyroidism, congenital, nongoitrous, 1 (TSHR)
• Hypothyroidism, congenital, nongoitrous, 4 (TSHB)
• Hypothyroidism, congenital, nongoitrous, 6 (THRA)
• Hypothyroidism, congenital, nongoitrous, 7 (TRHR)
• Hypothyroidism, congenital, nongoitrous, 8 (TBL1X)
• Immunodeficiency, common variable, 10 (NFKB2)
• Microphthalmia, syndromic 3 (SOX2)
• Microphthalmia, syndromic 5 (OTX2)
• Obesity, morbid, due to leptin receptor deficiency (LEPR)
• Optic nerve hypoplasia + abnormalities of the central nervous system (SOX2)
• Panhypopituitarism, XL (SOX3)
• Pituitary hormone deficiency, combined or isolated, 1 (POU1F1)
• Pituitary hormone deficiency, combined, 2 (PROP1)
• Pituitary hormone deficiency, combined, 3 (LHX3)
• Pituitary hormone deficiency, combined, 4 (LHX4)
• Pituitary hormone deficiency, combined, 5 (HESX1)
• Pituitary hormone deficiency, combined, 6 (OTX2)
• Retinal dystrophy, early-onset, with/-out pituitary dysfunction (OTX2)
• Septooptic dysplasia (HESX1)
• Thyroid hormone metabolism, abnormal (SECISBP2)
• Thyroid hormone resistance (THRB)
• Thyroid hormone resistance, AR (THRB)
• Thyroid hormone resistance, selective pituitary (THRB)
• obsolete designation: Deafness-thyroid hormone resistance syndrome (THRB)