Clinical characteristics: Poikiloderma with neutropenia (PN) is characterized by an inflammatory eczematous rash (appears at ages 6-12 months) followed by post-inflammatory poikiloderma (at age >2 years) and chronic noncyclic neutropenia typically associated with recurrent sinopulmonary infections in the first two years of life and (often) bronchiectasis. There is increased risk for myelodysplastic syndrome, acute myelogenous leukemia, and skin cancer. Other ectodermal findings include thickened nails, nail dystrophy, and palmar/plantar hyperkeratosis. Most affected individuals also have reactive airway disease, and some have short stature, hypogonadotropic hypogonadism, midfacial retrusion, calcinosis cutis, and non-healing skin ulcers.

Diagnosis/testing: Often the diagnosis of PN can be established in a proband based on clinical findings (post-inflammatory poikiloderma and congenital chronic neutropenia). Unequivocal confirmation of the diagnosis of PN relies on detection of biallelic USB1 pathogenic variants by molecular genetic testing.

Management: Treatment of manifestations: Dermatologic manifestations are treated with gentle skin care using bland emollients. Diligent sun protection with both UVA and UVB protection and/or sun-protective clothing to reduce the risk of skin cancer. Very pruritic palmar/plantar hyperkeratosis can be treated with a strong topical steroid or a topical keratolytic if secondary dermatophyte infection has been ruled out. Although use of granulocyte-colony stimulating factor increases the absolute neutrophil count, there is little evidence of decreased frequency of infections with this treatment. Sinopulmonary, middle ear, and skin infections require aggressive treatment with antibiotics. Annual influenza vaccine is recommended. Developmental support as needed. Gingivitis, dental caries, reactive airway disease, premyelodysplastic changes, myelodysplastic syndrome, acute myelogenous leukemia, skin cancer, hypogonadotropic hypogonadism, and osteoporosis are treated in the usual manner.

Surveillance: Annual examination by a physician familiar with PN; annual dermatology examination for skin cancer beginning at age ten years; dental examination every three to six months; annual pulmonology examination in those with bronchiectasis, chronic cough, and/or reactive airway disease; annual complete blood count with differential and platelet count with evaluation by a hematologist/oncologist as needed; assessment of growth, pubertal development, developmental milestones, and educational progress at each visit throughout childhood; DXA scan as needed in adults.

Agents/circumstances to avoid: Excessive sun exposure due to the increased risk of skin cancer; exposure to secondhand cigarette or wood smoke and persons with respiratory illnesses due to the increased risk of respiratory infections.

Evaluation of relatives at risk: It is appropriate to evaluate apparently asymptomatic older and younger sibs of a proband in order to identify as early as possible those who would benefit from prompt initiation of treatment and surveillance for potential complications.

Genetic counseling: PN is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a USB1 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the USB1 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal/preimplantation genetic testing are possible.