Dual Diagnosis of Nongoitrous Congenital Hypothyroidism-6 and Snijders Blok-Campeau Syndrome

• Published in: Molecular syndromology 2024-06, Vol.15 (3), p.240-246
• Main Authors: Yalçın, Hatice Yelda, Cinleti, Tayfun, Yel, Servet, Mutlu, Mehmet Burak
• Format: Article
• Language: English
• Subjects: Novel Insights from Clinical Practice
• ISSN: 1661-8769; 1661-8777
• DOI: 10.1159/000535682

Abstract Introduction: Nongoitrous congenital hypothyroidism-6 (CHNG6) is a thyroid hormone resistance syndrome caused by a thyroid hormone receptor alpha (THRA) gene mutation, characterized by tissue-specific hypothyroidism and near-normal thyroid function tests. Snijders Blok-Campeau syndrome (SNIBCPS) is a rare autosomal dominant neurodevelopmental disorder caused by mutations in CHD3 genes, characterized by intellectual retardation, hypotonia, speech problems, and distinctive facial findings. Case Presentation: We report a 3-year-old dual phenotype Turkish girl with novel variants both in the THRA and CHD3 genes, presenting with developmental delay, hypotonia, and congenital hypothyroidism. Thyroid function values were consistent with the laboratory findings of CHNG6 disease: high free tri-iodothyronine (fT3) level, normal free thyroxine (fT4) value, and suppressed thyroid-stimulating hormone (TSH) values (under treatment). Molecular studies revealed a novel heterozygous missense c.802 G>A (p.Asp268Asn) variant in THRA that was inherited from her mother and a novel de novo heterozygous frameshift c.4364-4367 del (p.Tyr1455CysfsTer28) variant in CHD3. Discussion/Conclusion: In the literature, there is no case of CHNG6 and SNIBCPS co-existence. Although these are distinct diagnosis, we present this case due to the concomitance of these diseases. Established FactsNongoitrous congenital hypothyroidism-6 (CHNG6) is a thyroid hormone resistance syndrome caused by thyroid hormone receptor alpha (THRA) gene mutation.Snijders Blok-Campeau syndrome (SNIBCPS) is a rare autosomal dominant neurodevelopmental disorder caused by mutations in the CHD3 gene.When THRA mutations are suspected, serum T3 and rT3 should be measured as well as T4 and TSH.