Gillespie syndrome: Greek patient with novel mutation and atypical presentation. Expansion of the phenotype and literature review

Introduction: Gillespie syndrome is characterized by bilateral aniridia, cerebellar hypoplasia leading to ataxia, congenital hypotonia, and variable degrees of intellectual disability. The condition is attributed to pathogenic variants in ITPR1, either in a biallelic manner or as heterozygous dominant-negative mutations. Case presentation: Herein, we report the case of a male neonate with generalized hypotonia, and bilateral aniridia, identified during routine newborn eye screening. His abdominal ultrasound revealed a left dysplastic pleiocystic kidney, and his brain MRI showed mega cisterna magna. In the second month of life, he presented with intestinal malrotation requiring surgical repair. Whole exome sequencing revealed a homozygous deletion of exons 3 and 4 in the ITPR1 gene, confirmed by molecular karyotype (array CGH). The patient was diagnosed with Gillespie syndrome, consistent with his ophthalmological and neurological findings. Conclusion: Urinary and gastrointestinal issues such as a pleiocystic kidney and malrotation have not previously been associated with Gillespie syndrome. While these findings may be coincidental, they could represent new phenotypic features of the condition.