Aniridia with PAX6 mutations and narcolepsy

• Published in: Journal of sleep research 2020-12, Vol.29 (6), p.e12982-n/a
• Main Authors: Berntsson, Shala Ghaderi, Kristoffersson, Anna, Daniilidou, Makrina, Dahl, Niklas, Ekström, Curt, Semnic, Robert, Markström, Agneta, Niemelä, Valter, Partinen, Markku, Hallböök, Finn, Landtblom, Anne‐Marie
• Format: Article
• Language: English
• Subjects: absence of iris; Adult; Aniridia - complications; Aniridia - genetics; Female; Humans; Middle Aged; Mutation; narcolepsy; Narcolepsy - genetics; Neurologi; Neurology; Oftalmiatrik; Ophtalmology; PAX6 haploinsufficiency; PAX6 Transcription Factor - genetics; pineal gland atrophy; Young Adult
• ISSN: 0962-1105; 1365-2869; 1365-2869
• DOI: 10.1111/jsr.12982

PAX6 gene mutations cause a variety of eye and central nervous system (CNS) abnormalities. Aniridia is often accompanied by CNS abnormalities such as pineal gland atrophy or hypoplasia, leading to disturbed circadian rhythm and sleep disorders. Less is known on the coincidence of narcolepsy in this patient group. We aimed to find out whether the circadian rhythm or sleep–wake structure was affected in patients with aniridia. Four members of a family segregating with congenital aniridia in two generations were included in the study. The patients were subjected to genetic testing for a PAX6 mutation, multiple sleep latency test, whole‐brain magnetic resonance imaging (MRI), hypocretin‐1 in cerebrospinal fluid, and Human Leukocyte Antigen DQ beta1*06:02. All four members were heterozygous for the pathogenic c.959‐1G>A mutation in the PAX6 gene. Sleep disturbance was observed in all family members. The index patient was diagnosed with narcolepsy. MRI showed a hypoplastic pineal gland in all members. We describe the first case of a patient with PAX6 haploinsufficiency, aniridia and pineal gland hypoplasia diagnosed with narcolepsy type‐1, suggesting a complex sleep disorder pathogenesis.