Hoyeraal-Hreidarsson syndrome: a case report of dyskeratosis congenita with a novel PARN gene mutation.

Introduction and importance: Dyskeratosis congenita (DC) is a rare multisystem disorder primarily characterized by bone marrow failure due to telomere shortening. Typical clinical features include oral leukoplakia, skin hyperpigmentation, and nail dystrophy, along with an increased risk of malignancies. Hoyeraal-Hreidarsson syndrome (HH), a severe variant of DC, is associated with profound neurological and immunological complications, emphasizing the importance of early diagnosis and genetic evaluation to guide appropriate management. Case presentation: The authors present a case of a 2-year-old girl diagnosed with Hoyeraal-Hreidarsson syndrome, linked to a newly discovered mutation in the poly (A)-specific ribonuclease (PARN) gene. The patient exhibited intrauterine growth retardation (IUGR), congenital cytomegalovirus (CMV) infection, immunodeficiency, microcephaly, and cerebellar hypoplasia. Whole-exome sequencing (WES) identified a novel mutation in the PARN gene. Clinical discussion: Hoyeraal-Hreidarsson syndrome, a severe form of DC, manifests with multisystem involvement and is genetically heterogeneous. Early genetic testing through techniques such as WES can aid in diagnosing rare syndromes like HH and guide treatment strategies, including bone marrow transplantation. Conclusion: This case underscores the importance of genetic evaluation in complex, rare syndromes like HH. Whole-exome sequencing plays a crucial role in identifying pathogenic mutations and tailoring management. The patient's prognosis is being closely monitored following bone marrow transplantation.