Objective: To describe a case with a homozygous c.132dupA ANO10 mutation.

Background: Autosomal recessive cerebellar ataxia type 3 (ARCA3) is associated to ANO10 mutations. It encodes a transmembrane protein, anoctamin 10, member of the calcium-activated chloride channels family. The c.132dupA mutation is regarded as the most common, but its homozygous presentation is extremely rare.

Method: Case report

Results: A woman initially complaining of blurred vision at 20 years of age, progressed to vertical binocular diplopia and oscillopsia with positional vertigo. The patient noticed a progressive course of gait instability and clumsiness since the age of 35 with frequent falls, followed by prominent urinary urge-incontinence. Dysphagia and memory difficulties were reported in follow-up visits. Her parents were consanguineous, two siblings died at birth. No other relevant family history. She had no past medical history other than thyroid nodules.
At 50 years of age, the patient presented to our movement disorders clinic. At clinical examination, she had titubation, gaze-evoked nystagmus, hypermetric saccades, slight right eye exotropia with vertical binocular diplopia, ataxic dysarthria, bilateral dysdiadochokinesia, limb and gait ataxia, requiring a unilateral support. Brisk tendon reflexes, Hoffmann sign bilaterally present but flexor plantar responses. Intolerance to dorsal decubitus due to rotational vertigo and conjunctival tortuous vessels were also noted.
Lab work-up including vitamins and α1-fetoprotein level were normal. Brain MRI revealed a diffuse cerebellar atrophy. Nerve conduction studies showed no evidence of neuropathy. Ophthalmic examination was normal. Previous genetic testing for SCA 1, 2, 3, 6, 17, and DRPLA was negative.
Exome sequencing revealed a homozygous ANO10 c.132dupA p.(Asp45Argfs*9) mutation.

Conclusion: We report the case of a woman with prominent cerebellar signs and pyramidal, ocular, vestibular, urinary and cognitive deficits associated to a homozygous ANO10 c.132dupA mutation. We could only find in the literature 4 families reported to have this homozygosity.
Besides the common cerebellar, pyramidal and cognitive impairment in the absence of neuropathy, the clinical picture we describe here is very uncommon in ARCA3. Our case contributes to further elucidate the phenotypic spectrum associated to ANO10 mutations, deepening our knowledge on the natural history of the disease and differential diagnosis of cerebellar ataxias.

« Back to MDS Virtual Congress 2020

MDS Abstracts - https://www.mdsabstracts.org/abstract/an-uncommon-clinical-phenotype-associated-with-ano10-mutation/