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.

Poikiloderma with neutropenia is an autosomal recessive condition characterized by postinflammatory poikiloderma and chronic neutropenia. To date, there is no published literature reporting on the impact of pregnancy on this rare genetic disorder. This case highlights a successful pregnancy outcome in a 26-year-old gravida 1 para 0 female with poikiloderma with neutropenia. Her pregnancy was complicated by thrombocytopenia, low fetal fraction, and high-risk cell-free DNA result. The findings of low fetal fraction and high-risk aneuploidy were unexpected given normal neonatal outcome. It is not yet well understood whether these findings are related to the genetic condition itself or use of medications used to manage her condition.

Poikiloderma with neutropenia (PN), also known as Clericuzio-type, is a rare autosomal recessive disorder characterized by immune system defects. This condition manifests in infancy with a distinctive rash that spreads over time, accompanied by various systemic symptoms, including recurrent infections and chronic neutropenia. Understanding this disorder is crucial for timely diagnosis and management, especially given its significant morbidity and potential mortality. We present a case of a 7-year-old Syrian male diagnosed with PN. He presented to the pediatric department with right flank pain, a triphasic fever pattern, dysuria, and dysphagia. His medical history included recurrent respiratory infections and a hyperpigmented rash since infancy. Clinical examination revealed significant symptoms, including developmental delays, pallor, and abnormal nails. The case emphasizes the clinical challenges in diagnosing PN, particularly given overlapping features with other inherited poikilodermas. Characteristic symptoms include the presence of poikiloderma, neutropenia, and recurrent infections. The autosomal recessive inheritance pattern noted in this case aligns with the documented familial patterns in existing literature. Clinicians must maintain a high index of suspicion and consider a comprehensive evaluation in patients exhibiting similar clinical signs to ensure accurate diagnosis and effective management. This Syrian case of PN illustrates how a carefully reasoned clinical diagnosis, in the absence of genetic testing, can guide effective care in low-resource contexts. It highlights pragmatic pathways (infection surveillance, antimicrobial escalation, and preventive counseling) that remain actionable even when confirmatory genetics are unavailable.

Poikiloderma with neutropenia is a genetic disorder characterized by skin abnormalities, nail dystrophy, bone anomalies, and neutropenia. USB1 encodes a phosphodiesterase essential for processing spliceosomal U6 RNA and some microRNAs, regulating their stability. This study describes a heterozygous de novo USB1 variant (p.P44L) identified in a patient with recurrent infections, hypogammaglobulinemia, and low neutrophil counts. Unlike previously reported mutations, p.P44L affects a conserved proline in the N-terminal domain, predicted to be critical for protein interactions and stability. Functional assays revealed that while U6 RNA processing remained intact, the variant altered protein interactions and subcellular localization, reducing nuclear presence and accumulation within nuclear speckles. In vitro, the variant did not prevent neutrophil differentiation but reduced clonal capacity. In zebrafish, it led to reduced neutrophils and pigmentation. These findings expand the spectrum of genetic traits associated with USB1 and suggest that a heterozygous variant affecting the N-terminal domain of USB1 impacts clinical phenotypes and that hypogammaglobulinemia may be associated with USB1 dysfunction.

Poikiloderma with neutropenia (PN) is a rare autosomal recessive disorder characterized by skin abnormalities, chronic neutropenia, and an increased risk of infections and malignancies. Patients typically present with poikiloderma, which includes hypopigmented and hyperpigmented macules, telangiectasia, atrophy, as well as nail thickening and palmoplantar hyperkeratosis. The condition is caused by pathogenic variants in the USB1 gene, which affects neutrophil function and immune response. Endocrine involvement, such as hypogonadism, may also occur. We present a 17-year-old male with a novel USB1 gene mutation (c.368T>C [p.Leu123Pro]), who exhibited typical dermatological features, including poikiloderma, nail thickening, and calcinosis cutis, in addition to hypogonadism. This case highlights the broad clinical spectrum of PN and the need for comprehensive care and surveillance.