Neonatal progeroid (Wiedemann-Rautenstrauch) syndrome: Report of five new cases and review

Abstract

The neonatal progeroid syndrome (NPS), or Wiedemann-Rautenstrauch, is a rare autosomal recessive disorder comprised of generalized lipoatrophy except for fat pads in the suprabuttock areas, hypotrichosis of the scalp hair, eyebrows, and eyelashes, relative macrocephaly, triangular face, natal teeth, and micrognathia. We report on 5 new patients who demonstrate phenotypic variability and who represent the single largest series of NPS reported to date. Two of the patients are from an African-American kindred, an ethnic occurrence not reported previously. The fact that there are 2 pairs of sibs among the 5 patients further supports that NPS is an autosomal recessive condition. This report also includes a review of the previously reported 16 patients and compares them with the 5 new patients. Abnormalities in endocrine and lipid metabolism were found in 3 of 5 patients. Skeletal findings in 2 of our patients demonstrated some new findings as well as the typical radiological abnormalities previously noted in NPS. It is apparent, based on the 21 cases, that mild to moderate mental retardation is common in NPS. Long term follow-up of patients with NPS should provide more information relative to their ultimate psychomotor development. NPS is usually lethal by 7 months; however, on rare occasions, patients have survived into the teens. Our 3 surviving patients range in age from 16-23 months. Variability in the phenotype of NPS is clear; however, the phenotype remains distinct enough to allow a secure diagnosis.

Thematic review series: Adipocyte Biology. Lipodystrophies: windows on adipose biology and metabolism

“…Affected individuals have progeroid features at birth, skull deformities, Lipodystrophies: windows on adipose biology and metabolismand generalized lipodystrophy fat loss (87). The molecular basis is unknown, but these patients have no mutations in known lipodystrophy genes or in candidate genes encoding nuclear envelope proteins (R. A. Hegele, unpublished observations).…”

LMNA is mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090)

“…This is associated with a spectrum of clinical features, including delayed psychomotor development and physical growth, alopecia, macrocephaly and lipoatrophy (Arboleda et al 1997;Bitoun et al 1995;Castineyra et al 1992;Devos et al 1981;Martin et al 1984;Pivnick et al 2000;Toriello 1990). No genomic DNA mutations have yet been reported in WRS, but because lipodystrophy is a central feature, genes that cause lipodystrophy can be considered as candidates.…”

Guilt by Association

“…The similarity of the lipocyte cells in liver to adipocytes has highlighted a group of NETs specific to fat cells (97) that are candidates for guilt by association in other inherited lipodystrophies (111)(112)(113)(114). The liver dataset could also be important for hepatic diseases.…”