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A form of severe short-limbed dwarfism with hair anomalies, defective immunity, and erythrogenesis.

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Metaphyseal Chondrodysplasia McKusick type.

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First recognized as a distinct entity in the Old Order Amish, a religious group in the United States, in 1965 by the American geneticist V.A. McKusick, who is also the founder and one of the editors of the “Online Mendelian Inheritance in Man" (OMIM) database.

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Clustering is found in Old Order Amish (1-2 in 1000 live births) and in certain areas of Finland (1 in 23,000 live births). It is very rare in other populations. No sexual predilection.

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Autosomal recessive with reduced penetrance. Caused by mutations of the mitochondrial RNA-processing endoribonuclease gene, which is located on 9p21-p12. This enzyme is responsible for cleavage of RNA in the mitochondrial DNA synthesis and for nucleolar cleaving of pre-rRNA.

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Defective cellular proliferation has been described affecting predominately T-cells (resulting in lymphopenia in almost two thirds of patients), but also involves B-cells (low serum concentrations of immunoglobulins A and/or G; in approximately one third of patients), neutrophils, and fibroblasts. This syndrome has been suggested to result from a generalized defect in cellular proliferation.

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Incomplete extension in the elbows, anterolateral chest deformity, genua varum, and excessive distal length of the fibula relative to the tibia are specific skeletal features. The major radiologic abnormalities are confined to the metaphyseal regions of tubular bones. Biopsy shows hypoplasia of cartilage to be the nature of the skeletal abnormalities.

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Radiographs show metaphyseal dysostosis. The disorder may involve the cervical spine (odontoid hypoplasia), the skeleton (short stature secondary to dwarfism with an adult height usually <135 cm, flaring of the lower rib cage at the costochondral junction, scoliosis, lumbar hyper-lordosis, platyspondylia, narrowed interpeduncular distances, small pelvic inlet, limited elbow extension, metaphyseal dysplasia, fibular length exceeding tibial length distally, short hands, brachydactyly, joint hyperextensibility), the viscera (Hirschsprung disease, esophageal atresia, anal stenosis, malabsorption), the teeth (microdontia, anomalies of the incisors and premolars), and the hair and skin (sparse, fine, light colored hair, redundant skin folds around the neck and the extremities, hypopigmentation, onychodysplasia). Laboratory investigations may show macrocytic anemia, neutropenia, lymphopenia, and cellular immunodeficiency. Recurrent pulmonary and opportunistic infections in these patients are common (mainly Candida albicans, Pneumocystis carinii, and Cytomegalovirus). Patients are predisposed to a severe course of Varicella infection (multiple fatalities have been reported) and malignancies (in approximately 5% of patients, mainly non-Hodgkin lymphomas). Susceptibility to infections usually improves in adulthood. The higher mortality in these patients compared to the general population mainly refers to children and is a result of the compromised immune system.

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Obtain a complete blood count with differentiation of red and white cells. The degree of anemia may correspond to the degree of immune deficiency. Anemia usually is mild, however, severe forms of hypoplastic anemia of childhood have been reported. Assess the airway for difficult intubation. Recurrent pulmonary infections warrant careful evaluation of pulmonary function (chest radiograph, arterial blood gas analysis, pulmonary function test). Check cardiac function to delineate the extent of cardiac compromise secondary to chest deformities and scoliosis (electrocardiography, echocardiography). If any concerns exist regarding the stability of the cervical spine, radiologic examinations should be performed.

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Strict aseptic technique during insertion of lines, performance of any regional blocks, and other invasive procedures is mandatory in the presence of immune deficiency. Lumbar spinal or epidural anesthesia may be difficult because of scoliosis, pronounced lumbar lordosis, and diminished interpeduncular distance. Venous access often is difficult because ...

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