Siblings with a Homozygous Variant in the NHP2 Gene: A Case Report and Review of Literature.

Introduction: Dyskeratosis congenita is a hereditary short telomere syndrome that is characterized by dysplastic nails, reticular pigmentation, oral leucoplakia and may have other progressive systemic manifestations. Here, we report two affected siblings in a family with dyskeratosis congenita.

Case presentation: A two-year-old girl (index patient) was admitted to our hospital with complaints of inability to walk and decreased vision, as well as developmental delay and cataracts. Her parents were consanguineous, and she had an 18-year-old brother with cataracts, intellectual disability, liver cirrhosis, pancytopenia, and hypersplenism. Magnetic resonance imaging of the brain of the index case revealed hypointense foci in the bilateral basal ganglia, thalamus, and parietal white matter, while the results of detailed metabolic tests were unremarkable. After 8 years of follow-up, the index patient was identified with additional findings that included intellectual disability, liver disease, pancytopenia, nail dystrophy, multiple foci of calcification on magnetic resonance imaging of the brain, while over the past 2 years, her brother developed nail dystrophy, oral leucoplakia, graying hair, and reticular pigmentation on his neck. Genome sequencing revealed a c.415T>C (p.Tyr139His) disease-causing variant in the NHP2 gene in the index case that was heterozygous in the parents and homozygous in the index case and her older brother.

Conclusions: In cases of multisystem involvement, consanguineous marriage, and multiple affected family members, patients may develop very rare diseases, such as dyskeratosis congenita, and physicians should be aware that new clinical findings may emerge during long-term follow-up, the diagnosis of which may count on genome sequencing.