Cerebellar Ataxia-deafness-narcolepsy (ADCA) syndrome. Description of a variable family phenotype

Cerebellar ataxia-deafness-narcolepsy syndrome (ADCA-DN) is a very rare polymorphic subtype of autosomal dominant ataxia type 1 (ADCA type 1). It begins in adulthood, and may also be associated with other variable symptoms as optic atrophy, cataracts, psychosis, depression or sensory neuropathy.

We present a family diagnosed from the first generation, its phenotypic description and genetic study.

We describe three members of a family with ADCA sydrome. Patient II-2 started at 51 years, with ataxia, tremor, epileptic seizures, cerebellar atrophy, narcolepsy without cataplexy, hearing loss, moderate cognitive impairment. Patient III-1 started at 42 years with narcolepsy with cataplexy, hearing loss and tremor, and patient IV-1 started at 4 years, with mild intellectual disability, and narcolepsy without cataplexy. Genetic test showed a mutation in DNMT1 gene: variant c.1709 C > T; p.Ala570Val in the DNMT1 gene.

ADCA syndrome has a variable phenotype in a same family. In our experience, this type of ataxia develops narcolepsy as the first sympton in all three cases, with tremor and cognitive impairment, together with tremor and cognitive impairment. Ataxia, despite being a cardinal symptom, does not appear at the onset in younger patients, and hearing loss also seems to develop over the years. Sensory neuropathy is not present in any of the cases studied.