Autosomal Dominant Obstructive Sleep Apnea Syndrome Due to the New Variant c.980_984dup in COL1A2: A Case Report.

Obstructive sleep apnea syndrome (OSAS) is a complex disorder characterized by the collapse of the upper airway during sleep. Although a family history often suggests a hereditary predisposition to OSAS, there is little evidence that it is actually a monogenic disorder. To date, no case of a patient with hereditary OSAS due to a pathogenic mutation in the collagen type I alpha-2 chain (COL1A2) gene has been described. The patient was a 72-year-old woman who had suffered from insomnia since the age of 35. OSAS was suspected since then, but was only confirmed at the age of 67 by polysomnography. The OSAS was treated with nocturnal active positive airway pressure (APAP), which led to an improvement. Her medical history also included joint hypermobility, brachydactyly, multiple nevi, an umbilical hernia, left-sided tinnitus and hearing impairment, hair loss, hip pain, and ptosis. Since her son also developed OSAS at the age of 34, hereditary OSAS was suspected, and exome sequencing was performed, which revealed the novel variant c.980_984dup (p.Ile329Alafs*72) in the COL1A2 gene. Since OSAS is a known complication of connective tissue disorders (CTDs), the index patient's OSAS was attributed to the COL1A2 mutation. This case suggests that OSAS may be hereditary due to a variant in the COL1A2 gene and may represent the dominant phenotypic feature. Physicians should be aware that OSAS can be hereditary; therefore, CTD patients with a positive family history of OSAS should undergo genetic testing for variants in genes associated with CTD.