Subtypes of<unk>  OMIM Name Gene Chromosome Gene/Locus MIM number<unk> 1 ELANE 19p13.3 130130<unk> 2 GFI1 1p22.1<unk> 3 HAX1 1q21.3<unk> 4 G6PC3 17q21.31<unk> 5 VPS45 1q21.2<unk> X WASP Xp11.23 300392 The most common form,<unk> 1, is autosomal dominant. Kostmann disease, which is<unk> 3, is inherited in an autosomal recessive pattern. Kostmann disease,<unk> 3, is inherited in an autosomal recessive manner, but the commonest subtype of Kostmann syndrome,<unk> 1, is autosomal dominant. A significant proportion of<unk>  lacks a known mutation. The recognized subtypes of Kostmann syndrome are: *<unk> 1 is the commonest form of<unk> , which accounts for 60-80% of<unk> , and the first to be genetically typified. This autosomal dominant form that arises from mutations of the ELANE (formerly ELA2) gene on chromosome 19p13.3, which encodes neutrophil elastase. Over a hundred ELANE mutations have been found in<unk> 1. This same gene is mutated in cyclic<unk> . *<unk> 2 is caused by heterozygous (autosomal dominant) mutation of the GFI1 gene on chromosome 1p22. GFI1 is a repressor of<unk> l transcriptional processes, including ELANE, as well as miR-21 and miR-196b micro-RNAs which influence myelopoiesis. *<unk> 3 is the "classical", autosomal recessive form of Kostmann disease which arises from homozygous mutations in the HAX1 gene on chromosome 1p22.1. About one third of<unk> 3 individuals also have neurological changes including seizures, learning disabilities, or developmental delay. *<unk> 4 is caused by autosomal recessive mutation of the G6PC3 gene on 17q21.<unk> 4 is associated with structural cardiac abnormalities, enlarged liver, intermittent thrombocytopenia and a prominent superficial venous pattern. A subset of<unk> 4 has<unk>  primary pulmonary hypertension and respiratory failure. *<unk> 5 arises from autosomal recessive Thr224Asn mutation in the VPS45 gene on chromosome 1q21.2. Unlike classical Kostmann disease,<unk> 5 also has defective platelet aggregation (thrombasthenia) and myelofibrosis. This type is refractory to granulocyte colony-stimulating factor. There is an absence of lysosomes in fibroblasts and depletion of alpha granules in platelets. Accelerated apoptosis occurs in the neutrophils and bone marrow. * X-linked<unk>  <unk> X) is caused by mutation in the WASP gene on Xp11.<unk>  occasionally may arise from SBDS mutations. Usage<unk>  <unk>  is used as the overarching term for all diseases that affect myelopoiesis most prominently. Kostmann syndrome can restrictively refer to Kostmann disease specifically, or can be used synonymously with<unk>  as an umbrella term. These syndrome subtypes are phenotypically similar despite arising from different gene abnormalities. Kostmann disease is a form of<unk>  <unk> , specifically type 3 <unk> 3), which is a rare autosomal recessive condition in which<unk>  chronic<unk>  is detected soon after birth. The disorder was discovered in 1956 in an extended family in northern Sweden by Rolf Kostmann, a Swedish doctor. Although mutations of more than 15 genes cause<unk>  (in a general sense) not all of these are usually considered as<unk> . Clinical usage excludes two broad categories of<unk><unk> . Diseases are excluded that overtly affect multiple systems rather than impacting myelopoiesis most prominently. Thus<unk>  excludes the<unk><unk>  which can occur in<unk>  diseases such as Shwachman–Diamond syndrome, Barth syndrome, Chédiak–Higashi syndrome, WHIM syndrome, and glycogen storage disease type Ib. A further group of other miscellaneous inherited disorders, such as hyper IgM syndrome, Hermansky–Pudlak syndrome (HPS), Griscelli syndrome (GS), PN, P14 deficiency, Cohen syndrome, Charcot–Marie–Tooth disease (CMT) can show<unk><unk> , but lack bone marrow findings typical of<unk> . This group of diseases may also have additional features such as partial albinism, retinopathy, or neuropathy, and are not inclined to degenerate into acute myelogenous leukemia. GATA2 deficiency GATA2 deficiency is a grouping of<unk> l disorders caused by common defect, viz., familial or sporadic inactivating mutations in one of the two parental GATA2 genes. These autosomal dominant mutations cause a reduction, i.e. a haploinsufficiency, in the cellular levels of the gene's product, GATA2. The GATA2 protein is a transcription factor critical for the embryonic development, maintenance, and functionality of blood-forming, lympathic-forming, and other tissue-forming stem cells. In consequence of these mutations, cellular levels of GATA2 are deficient and individuals develop over time hematological, immunological, lymphatic, or other presentations that may begin as apparently benign abnormalities but commonly progress to a more serious disorder. A small but significant percentage of individuals with GATA2 deficiency's present with<unk><unk> . This<unk>  is typically mild, often persists for years, and therefore is not a Kostmann syndrome disorder. Over time, however, the deficiency commonly progresses to include thrombocytopenia, increases susceptibility to infections due to, e.g. atypical mycobacteria or human papillomavirus, dysfunction of non-hematological organs, the myelodysplastic syndrome, and/or a leukemia, particularly acute myelogenous leukemia.
Severe congenital neutropenia
Autoimmune neutropenia
Bare lymphocyte syndrome
Diffuse infiltrative lymphocytosis syndrome
Adult-onset immunodeficiency syndrome
Refractory cytopenia of childhood
Leukocyte adhesion deficiency
Myelodysplastic syndrome