Insights Into Poikiloderma With Neutropenia: Genotypic and Phenotypic Analysis of 90 Cases With a New Case Report

Poikiloderma with neutropenia (PN) is a rare autosomal recessive disorder characterized by poikiloderma, neutropenia, and recurrent infections. We present a patient with PN carrying a novel homozygous pathogenic variant in the USB1 gene (c.547delC, p.Leu183Trpfs82*), and reviewed 90 PN cases reported since 1991 (including one new case) in order to assess genotype-phenotype correlations. Early symptoms included erythematous rash and recurrent infections (44% and 27% at 6 months, respectively), poikiloderma (88% at 12 months), and hepatosplenomegaly or elevated liver enzymes (22% at 12 months). Photosensitivity (21%) had a median onset at 21 months. Nail dystrophy and palmoplantar hyperkeratosis emerged later (36-48 months). Growth delay occurred in 53%, and 54% showed dental anomalies such as caries, hypodontia, or peg-shaped teeth. Notably, 17% developed malignancies-four non-melanoma skin cancers and 11 hematologic malignancies (AML, MDS, or pre-MDS), highlighting a significant oncogenic risk. Genetic analysis revealed 34 different pathogenic variants in the USB1 gene. Our findings underscore the importance of early recognition and long-term cancer surveillance in PN patients and provide a foundation for further research into USB1's role and the disorder's progression.