PN is caused by pathogenic variants in USB1 on chromosome 16. PN is inherited in an autosomal recessive manner, as documented in certified GeneReviews genetic counseling data; the parents of an affected individual are presumed to be heterozygous carriers of USB1 pathogenic variants. A family history consistent with autosomal recessive inheritance - such as affected siblings or parental consanguinity - supports the clinical diagnosis, though absence of family history does not exclude the diagnosis. The disorder has been identified in multiple ethnicities, with a particularly prevalent pathogenic variant documented among individuals of Turkish ancestry.

According to certified GeneReviews data, PN should be suspected in individuals presenting with the combination of (1) an eczematous acral rash beginning between 6 and 12 months of age that progresses to post-inflammatory poikiloderma after age two years, and (2) congenital chronic noncyclic neutropenia of moderate to severe degree, defined as an absolute neutrophil count (ANC) below 1,000 cells per microliter, with severe neutropenia defined as ANC below 500 cells per microliter. Additional supporting features include recurrent sinopulmonary infections and ectodermal findings such as nail dystrophy and palmar/plantar hyperkeratosis. Family history consistent with autosomal recessive inheritance provides further support. The GeneReviews chapter notes that, prior to the availability of USB1 molecular genetic testing, individuals with PN were frequently misdiagnosed with Rothmund-Thomson syndrome, dyskeratosis congenita, and Kindler syndrome, a subtype of epidermolysis bullosa. Molecular genetic testing of USB1 confirms the diagnosis and enables identification of at-risk family members.

According to certified GeneReviews management data, initial evaluation following diagnosis of PN encompasses multiple organ systems: dermatologic evaluation for calcinosis cutis, cellulitis, palmar/plantar hyperkeratosis, non-healing ulcers, and evidence of skin malignancy; dental evaluation for gingivitis and caries; otolaryngology assessment for complications of chronic otitis media; and pulmonary consultation. The GeneReviews surveillance protocol describes annual physical examination by a clinician familiar with PN; annual dermatologic examination for skin cancer beginning at age 10 years; dental evaluation every 3 to 6 months; and annual or more frequent pulmonary evaluation in individuals with bronchiectasis, chronic cough, or reactive airway disease. Assessment for hematologic malignancy progression, including myelodysplastic syndrome, is described as part of ongoing monitoring. No disease-specific pharmacologic agents directed at the underlying molecular deficit of PN are identified in this packet.

According to certified GeneReviews clinical data, PN is associated with an elevated risk for myelodysplastic syndrome - which may progress to acute myelogenous leukemia - and for skin squamous cell carcinoma; malignancies are reported in approximately 5-10% of affected individuals in the clinical series. Bronchiectasis resulting from recurrent sinopulmonary infections represents an additional source of long-term morbidity. Intrafamilial clinical variability has been documented, indicating that phenotypic severity is not fully determined by genotype alone. No quantitative survival or life expectancy data specific to PN are provided in this packet.

No clinical trial details specifically for poikiloderma with neutropenia are available in this packet. The classified research publication landscape for PN encompasses 106 publications, with reviews and meta-analyses constituting the dominant publication type (46 reviews); 13 case reports are also documented. Biomarker publications and gene therapy publications are noted in the landscape digest, reflecting an emerging investigational literature. The GeneReviews chapter does not identify specific therapies under investigation for PN. For current clinical trial enrollment information, the ClinicalTrials.gov registry is the authoritative reference source for this condition.