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

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.

Keywords: CHD3; Novel; Snijders Blok-Campeau syndrome; THRA.

Fig. 1.

Phenotypic features of the patient. Note hypertelorism, round and flat face, frontal bossing, full cheeks, wide and short nasal bridge, thin upper lip, micrognathia, tapering fingers, and brachydactyly on hands and feet.

Fig. 2.

Bone radiographs of the patient. A lateral skull radiograph (a) of the patient shows thickened skull vault (white arrow) and mild macrocephaly. b Bilateral coxa valga deformity and cortical thickening of long bones (white arrows). The black arrow in (c) indicates scoliosis.

Fig. 3.

Molecular results of the patient and her mother. Patient: CHD3: c.4364-4367 del (p.Tyr1455CysfsTer28). Mother and patient: THRA: c.802G>A (p.Asp268Asn).

Fig. 4.

Schematic view of the CHD3 protein with colored boxes corresponding to the protein domains listed in the included key. The CHD3 variant in our patient was in the DUFs domain indicated by black dot. Other previously reported variants in the DUFs domain are indicated by orange dots.