Objective: Our aim was to report the clinical and paraclinical findings from two siblings who presented with a new phenotype of ATP8A2 gene mutation.

Background: Mutations in ATP8A2 have been described in a number of patients with severe, early-onset hypotonia and cognitive impairment. Recent studies are broadening the clinical phenotype of this mutation

Method: Our patients were followed for 12 years. Whole exome sequencing (WES) was performed on genomic DNA obtained from patients’ blood, following a standard protocol and after parental consent. We described their clinical, biological, electrophysiological and neuro-imaging findings, and compared them with the literature.

Results: We report the case of two siblings (20 and 12 years-old girl and boy) from a third-degree consanguineous marriage, followed in our department since the ages of three and eight. Both presented with severe hypotonia in their first year of life, and developmental delay. At the age of four, they developed generalized and severe dystonia and choreiform movements in the upper limbs. Both had spastic tetraplegia, ophthalmoplegia, and optic atrophy. Brain imaging revealed cerebral atrophy. Brainstem-evoked response audiometry showed bilateral profound deafness. WES performed on the girl revealed biallelic ATP8A2 mutation.

Conclusion: To our knowledge, this is the first Tunisian family reported in literature with ATP82A mutation. Recent advances have enabled to broaden the phenotypic spectrum of ATP82A-related diseases. ATP82A clinical spectrum remains unexplored and further genetic studies are essential to better understand these complex disorders.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/atp8a2-mutation-in-a-tunisian-family-expanding-the-clinical-spectrum/