Transient progeroid phenotype and lipodystrophy in mosaic polyploidy
University of Pécs, Medical Faculty, Department of Medical Genetics and Child Development, Pécs, Hungary.Clinical Dysmorphology (Impact Factor: 0.61). 02/2006; 15(1):29-31. DOI: 10.1097/01.mcd.0000175605.10844.3e
Wiedemann-Rautenstrauch syndrome is a rare disorder with a progressive course and early lethality. Severe mental and growth retardation, muscle hypotonia, a progeroid face, wrinkled skin, relative macrocephaly with late closure of the anterior fontanel, arachnodactyly and congenital heart defects are also typical. We report on a female infant with all the characteristic features of this syndrome after birth. Chromosomal studies on peripheral leukocytes showed a normal karyotype. In view of an abnormal lipid distribution and lipodystrophy, metabolic studies for congenital disorders of glycosylation have been performed with normal results. At the age of 2 years 6 months the progeroid signs were no longer present, and the patient had a striking improvement in her psychomotor development. As there are overlapping features in Wiedemann-Rautenstrauch syndrome and in mosaic polyploidy, including psychomotor retardation, reduced peripheral muscle bulk, arachnodactyly and lipodystrophy, chromosome analysis was performed in the fibroblast culture of our patient. A mosaic triploidy/tetraploidy was detected in 60% and 14% of the cells, respectively. We therefore recommend chromosome analysis of fibroblasts from patients with a neonatal presentation of progeroid features and lipodystrophy.
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ABSTRACT: Neonatal progeroid syndrome (NPS), also known as Wiedemann-Rautenstrauch Syndrome, is a rare autosomal recessive disorder characterized by accelerated aging and lipodystrophy from birth. Affected children have extreme intrauterine growth retardation, poor postnatal weight gain, and characteristic facial dysmorphic features such as a triangular shape, pinched nose, pseudohydrocephalus with wide fontanelles and prominent subcutaneous (sc) veins. Generalized loss of sc fat has been reported as a cardinal feature; however, the pattern of fat loss and its association with insulin resistance and its metabolic complications have not been systematically studied. The aim of the current study was to examine body fat distribution and body composition in two girls with NPS using anthropometric measures, whole-body magnetic resonance imaging (MRI) and dual energy X-ray absorptiometry (DEXA), and to assess metabolic complications such as hyperinsulinemia and dyslipidemia. Both the girls (aged 17 years and 10 years, respectively) had generalized paucity of sc fat on physical examination. However, measurements of skin-fold thickness revealed that sc fat was decreased over the extremities, but preserved over the chest and abdomen. MRI studies confirmed the presence of normal amounts of sc truncal fat, and marked loss of fat from the face and distal extremities. Striking fat loss was also noted in the paravertebral and lateral gluteal regions. Interestingly, body composition analysis with DEXA scan revealed a marked reduction in both the fat and lean tissue mass. Fasting glucose, lipids and insulin levels were not elevated. We conclude that patients with NPS do not have generalized lipodystrophy as previously reported, but fat loss is confined to the face, distal extremities, and possibly the paravertebral and lateral gluteal regions. Metabolic abnormalities related to insulin resistance are also uncommon in this condition.
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ABSTRACT: This report presents the case of a 15-year-old male with severe chronic neutropenia, leukopenia, and persistent tetraploid mosaicism in the bone marrow and peripheral blood. His father had mild neutropenia and bone marrow tetraploidy. Flow cytometric analysis of DNA content peripheral blood showed tetraploidy in 20% of granulocytes and 15% of monocytes. Sequence analysis of the ELA2 gene was normal, but the GFI1 gene exhibited transient appearance of single base changes the coding region and promoter. We speculate that an underlying genetic defect, inherited in an autosomal dominant pattern, leads to both disordered mitosis and neutropenia in this kindred.
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