Autosomal dominant transmission of congenital hypothyroidism, neonatal respiratory distress, and ataxia caused by a mutation of NKX2-1.

Objective: To study the NKX2-1 gene in two half-siblings with elevated thyroid-stimulating hormone (TSH) on state screen, prolonged neonatal respiratory distress despite term gestations, and persistent ataxia, dysarthria, and developmental delay.

Study Design: We amplified and sequenced DNA samples from blood or buccal swab for subjects and their unaffected siblings.

Results: The same mutation that prevents splicing together of exons 2 and 3 of the NKX2-1 gene was present in the affected siblings, their mother, and maternal grandmother but not in their unaffected siblings. The mutation was present in the heterozygous form, thus explaining the disease phenotype.

Conclusions: Autosomal dominant transmission of mutations of NKX2-1 may cause congenital hypothyroidism, neonatal respiratory distress at term, and persistent neurologic findings such as ataxia, choreoathetosis, and dysarthria in families with affected subjects in multiple generations.