Headache and Sleep-Related Breathing Disorders Among Patients With Sclerosteosis and Disease Carriers: The First Family in Italy

BackgroundHeadache and sleep-related breathing disorders among patients with sclerosteosis and disease carriers has been little studied. We investigated the neurological and neuroimaging features of patients and gene carriers of a large Italian family with sclerosteosis.Main bodyIn this Italian family with sclerosteosis, genetic tests detected the homozygous mutation p.Gln24X (c.70C>T) of the SOST gene in the proband, and a heterozygous mutation between 9 siblings. Severe hyperostosis of the skull caused chronic headache secondary to intracranial hypertension due to venous hypertension and obstructive sleep apnea syndrome in adult homozygotes. There was transosseous intracranial-extracranial occipital venous drainage which indicated a compensatory mechanism for intracranial venous hypertension, one of the causative factors of increased CSF pressure in sclerosteosis. While mild hyperostosis of the skull was associated with headache and snoring in heterozygotes. ConclusionsHeadache and sleep-related breathing disorders are the most common clinical manifestations among patients with sclerosteosis and disease carriers. Cerebral venous hypertension leading to intracranial hypertension and facial deformities are the causative factors of headache and sleep-related breathing disorders. These data suggest that venous stenting to accommodate cerebral venous drainage could be useful in the treatment of intracranial hypertension, and correction of facial deformities to relieve obstructive sleep apnea may play a role in the treatment of patients with sclerosteosis. The data highlight that it is reasonable to extend neurological evaluation and radiological study to gene carriers.