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Birth prevalence | 0.5–2.5 per 105 newborns; varies with ethnic background. |
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Mode of inheritance | Autosomal recessive (>98%) and X-linked (~1-2%). |
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Carrier frequency | Traditional overall estimate: “1/300 worldwide.” Needs reassessment according to subtype and ethnic background. |
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Congenital abnormalities* | Radial ray abnormalities (aplastic or hypoplastic radii and absent or extra thumbs) and other skeletal abnormalities; small head circumference; abnormal shape of the ears; microphthalmia; ectopic or horse-shoe kidney; hypogonadism; heart abnormalities; intestinal or anal atresia. |
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Other somatic abnormalities* | Short stature/retarded growth; reduced fertility; skin pigmentation abnormalities (hyperpigmentation, café-au-lait spots); deafness. Endocrinopathy affecting the pancreas (diabetes mellitus), growth hormone deficiency, and hypothyroidism; early menopause. |
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Hematological symptoms | Bone marrow failure or aplastic anemia typically starting at 5–10 years with thrombocytopenia. Exception: D1 and N patients may die before that age from AML or other childhood solid tumors (such as medullo- or nephroblastoma). |
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Cancer risk | 800-fold increased risk of AML, mostly occurring at age 5–15 years, typically after the onset of marrow failure. At older ages there is a similarly increased risk of solid tumors, mainly carcinomas of the head and neck or oesophagus, as well as, in females, the vulva and vagina. D1 and N patients typically develop malignancies during early childhood (<5 years). |
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Overlapping syndromes** | Inherited bone marrow failure syndromes: Dyskeratosis congenita, Diamond-Blackfan anemia, Shwachman-Diamond syndrome, severe congenital neutropenia, thrombocytopenia absent radii (TAR) syndrome, amegakaryocytic thrombocytopenia.Other overlapping syndromes: Baller-Gerold syndrome, Nijmegen breakage syndrome, Rothmund-Thomson syndrome, Roberts syndrome, Warsaw Breakage syndrome, DK-phocomelia, VACTERL hydrocephalus syndrome, Wiskott-Aldrich syndrome. |
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