Brain-lung-thyroid syndrome: clinical response under methylphenidate hydrochloride therapy

INTRODUCTION: The “brain-lung-thyroid syndrome” is caused by mutations in the NKX2-1 gene, which encodes the thyroid transcription factor 1, and is characterized by widely diverse clinical manifestations: choreic movements, respiratory disorders and hypothyroidism. CASE REPORT: Male patient, 10 years old, son of non-consanguineous parents, being treated for subclinical hypothyroidism with levothyroxine, was referred at 4 years of age for investigation of hypotonia. There were no reports of breathing problems at birth. Investigation for hypotonia (central and neuromuscular) including muscle biopsy was normal. There was a progressive improvement in hypotonia, but the patient developed choreic movements. In view of the new clinical finding, a genetic-molecular study was carried out directed towards the NKX2-1 gene, confirming the diagnosis of “brain-lung-thyroid syndrome”. The patient started treatment with methylphenidate hydrochloride with evident improvement in choreic movements. DISCUSSION: Manifestations related to the NKX2-1 gene may include hereditary benign chorea (HBC), congenital hypothyroidism and neonatal respiratory disorders. Generally, chorea begins in early childhood, in the patient’s first year of life (most common), in later childhood or even adolescence, and progresses into the second decade after which it remains static or (rarely) resolves. Recently, the use of methylphenidate in patients with a mutation in this gene proved to be a possible therapeutic approach to control choreic movements and improve motor coordination in patients affected by this rare disease.