Multilocus Genetic Variants in a Child with Neuro-Ichthyosis: A Case of Pharmacoresistant Epilepsy and Developmental Delay Associated with CC2D2A, ABCA12, DOCK6 Variants, and a 14q31.3–q32.11 Deletion

Background: Neuro-ichthyosis is a rare and heterogeneous group of disorders characterized by concurrent neurological dysfunction and ichthyotic skin changes. This report describes an unprecedented constellation of multilocus genetic abnormalities—homozygous CC2D2A variant, heterozygous ABCA12 and DOCK6 variants, and a 14q31.3–q32.11 deletion—in a child with pharmacoresistant epilepsy, severe developmental delay, and ichthyosis. This combination has not been previously documented, adding new insight into multilocus contributions to neurocutaneous syndromes. Case Presentation: A 5-year-old girl, born to consanguineous parents, presented with generalized tonic–clonic seizures, microcephaly, global developmental delay, and ichthyosis. Family history was significant for similarly affected siblings. Despite multiple antiepileptic drugs, seizures remained refractory. Whole exome sequencing revealed a homozygous CC2D2A mutation consistent with Joubert syndrome type 9, along with heterozygous ABCA12 and DOCK6 variants and a pathogenic 14q31.3–q32.11 deletion. Conclusion: This case expands the genotypic and phenotypic spectrum of neuro-ichthyosis. To our knowledge, this is the first report of concurrent CC2D2A, ABCA12, DOCK6 variants, and a 14q deletion in a single patient not previously reported. These findings highlight the potential role of multilocus pathogenicity in shaping complex neurocutaneous phenotypes and reinforce the importance of early genetic testing for diagnosis and counseling.