Poikiloderma with Neutropenia (PN)

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Disease Ontology 12 DOID:0060551 OMIM® 57 604173 KEGG 36 H00793 MeSH 44 C565820 D012868 ICD10 32 D82.8

ICD10 via Orphanet 33 D82.8 UMLS via Orphanet 71 C1858723 Orphanet 58 ORPHA221046 MedGen 41 C1858723 SNOMED-CT via HPO 68 128601007 16294009 165517008 194021007 195788001 22006008 231796003 237836003 258211005 402685001 41446000 699014000 70114006 9826008 more

MedlinePlus Genetics : ⁴³ Poikiloderma with neutropenia (PN) is a disorder that mainly affects the skin and the immune system. This condition begins with a bumpy rash that usually appears between the ages of 6 and 12 months, gradually spreading from the arms and legs to the torso and face. At about age 2, the rash fades, and the affected child is left with darker and lighter patches of skin coloring (hyperpigmentation and hypopigmentation) and small clusters of blood vessels just under the skin (telangiectases); this combination is known as poikiloderma. Other skin problems include unusually thick skin on the palms of the hands and soles of the feet (palmoplantar keratoderma); calcium deposits that form small nodules (calcinosis cutis), especially on the knees, elbows, or ears; or sores (ulcers) that do not easily heal. Affected individuals also have fingernails and toenails that are thick and abnormally shaped (pachyonychia), fragile teeth, and low bone density.People with PN have chronic neutropenia, which is a persistent shortage (deficiency) of neutrophils. Neutrophils are a type of white blood cell that plays a role in inflammation and in fighting infection. Neutropenia makes it more difficult for the body to fight off pathogens such as bacteria and viruses. As a result, people with PN experience recurrent sinus infections and pneumonia, especially in the first few years of life. They often develop a condition called bronchiectasis, which damages the passages leading from the windpipe to the lungs (bronchi) and can cause breathing problems. The infections become less frequent after early childhood, but throughout life affected individuals usually have a chronic cough or a reactive airway disease. This term describes asthma and other conditions in which the airways abnormally constrict in response to stimuli such as smoke or a viral infection, leading to wheezing and shortness of breath.Researchers suggest that PN may increase the risk of cancer, although the level of risk is difficult to determine because only a small number of people have been diagnosed with PN. A type of skin cancer called squamous cell carcinoma, a precancerous blood disorder known as myelodysplastic syndrome (MDS), and a blood cancer called acute myelogenous leukemia that often follows MDS have occurred in a few people with PN.Some individuals with PN also develop unusual facial features as they grow. These features include a prominent forehead (frontal bossing), widely spaced eyes (hypertelorism), a flat or sunken appearance of the middle of the face (midface hypoplasia), a small nose with a depressed nasal bridge, and a chin that protrudes (prognathism). Short stature and hypogonadotropic hypogonadism (a condition affecting the production of hormones that direct sexual development) can also occur in this disorder.

MalaCards based summary : Poikiloderma with Neutropenia, also known as poikiloderma with neutropenia, clericuzio type, is related to neutropenia and rothmund-thomson syndrome, type 2. An important gene associated with Poikiloderma with Neutropenia is USB1 (U6 SnRNA Biogenesis Phosphodiesterase 1), and among its related pathways/superpathways is mRNA Splicing - Major Pathway. Affiliated tissues include skin, neutrophil and bone marrow, and related phenotypes are hypertelorism and malar flattening

Disease Ontology : ¹² A skin disease characterized by poikiloderma, hyperkeratotic nails, generalized hyperkeratosis on palms and soles, neutropenia, short stature, and recurrent pulmonary infections and has material basis in mutation in the C16ORF57 gene on chromosome 16q13.

GARD : ²⁰ The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 221046 Definition Poikiloderma with neutropenia is a rare, genetic hereditary poikiloderma disorder characterized by early-onset poikiloderma (which typically begins in the extremities, progresses centripetally and eventually involves the trunk, face and ears) associated with chronic neutropenia, recurrent infections, pachyonychia and palmoplantar keratoderma. Growth and/or develomental delay and hepato- and/or splenomegaly are additional reported features.

OMIM® : ⁵⁷ Poikiloderma with neutropenia (PN) is an autosomal recessive syndrome characterized by poikiloderma, hyperkeratotic nails, generalized hyperkeratosis on palms and soles, noncyclic neutropenia, short stature, and recurrent pulmonary infections (Clericuzio et al., 1991). (604173) (Updated 05-Apr-2021)

KEGG : ³⁶ Poikiloderma with neutropenia is an inherited genodermatosis found in Navajo people. It is characterized by erythematous rash that appears in the first year of life. The rash starts from the limbs and spreads to the trunk and the face, evolving into poikiloderma. Patients with this disease have recurrent bacterial infections and chronic neutropenia. It has been reported mutations in USB1 cause this condition.

UniProtKB/Swiss-Prot : ⁷² Poikiloderma with neutropenia: A genodermatosis characterized by poikiloderma, pachyonychia and chronic neutropenia. The disorder starts as a papular erythematous rash on the limbs during the first year of life. It gradually spreads centripetally and, as the papular rash resolves, hypo- and hyperpigmentation result, with development of telangiectasias. Another skin manifestation is pachyonychia, but alopecia and leukoplakia are distinctively absent. Patients have recurrent pneumonias that usually result in reactive airway disease and/or chronic cough. One of the most important extracutaneous symptoms is an increased susceptibility to infections, mainly affecting the respiratory system, primarily due to a chronic neutropenia and to neutrophil functional defects. Bone marrow abnormalities account for neutropenia and may evolve into myelodysplasia associated with the risk of leukemic transformation. Poikiloderma with neutropenia shows phenotypic overlap with Rothmund- Thomson syndrome.

GeneReviews: NBK459118

Clinical features from OMIM®:

604173 (Updated 05-Apr-2021)

#	Description	GenomeRNAi Source Accession	Score	Top Affiliating Genes
1	Decreased shRNA abundance	GR00251-A-1	9.62	CDC5L G6PC3 PLRG1 PRPF19 RNU5A-1
2	Decreased shRNA abundance	GR00251-A-2	9.62	CDC5L G6PC3 PLRG1 PRPF19 RNU5A-1

Search Clinical Trials , NIH Clinical Center for Poikiloderma with Neutropenia

Search GEO for disease gene expression data for Poikiloderma with Neutropenia.