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

Abstract

<b><i>Introduction:</i></b> Nongoitrous congenital hypothyroidism-6 (CHNG6) is a thyroid hormone resistance syndrome caused by a thyroid hormone receptor alpha (<i>THRA</i>) 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 <i>CHD3</i> genes, characterized by intellectual retardation, hypotonia, speech problems, and distinctive facial findings. <b><i>Case Presentation:</i></b> We report a 3-year-old dual phenotype Turkish girl with novel variants both in the <i>THRA</i> and <i>CHD3</i> 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&gt;A (p.Asp268Asn) variant in <i>THRA</i> that was inherited from her mother and a novel de novo heterozygous frameshift c.4364-4367 del (p.Tyr1455CysfsTer28) variant in <i>CHD3</i>. <b><i>Discussion/Conclusion:</i></b> 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.