Wiedemann–Rautenstrauch syndrome: A phenotype analysis. Issue 7 (26th April 2017)

• Record Type: Journal Article
• Authors: Paolacci, Stefano; Bertola, Debora; Franco, José; Mohammed, Shehla; Tartaglia, Marco; Wollnik, Bernd; Hennekam, Raoul C.
• Is Part Of: American journal of medical genetics. Volume 173:Issue 7(2017)
• Page Start: 1763
• Page End: 1772
• Publication Date: 2017-04-26
• Subjects: 4H syndrome -- autosomal recessive -- cerebellar hypoplasia‐endosteal sclerosis -- lipodystrophy -- POLR3A -- POLR3B -- Wiedemann–Rautenstrauch syndrome; Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.38246
• Languages: English
• ISSNs: 1552-4825

Abstract

Abstract : Wiedemann–Rautenstrauch syndrome (WRS) is a neonatal progeroid disorder characterized by growth retardation, lipodystrophy, a distinctive face, and dental anomalies. Patients reported to date demonstrate a remarkable variability in phenotype, which hampers diagnostics. We performed a literature search, and analyzed 51 reported patients, using the originally reported patients as "gold standard." In 15 patients sufficient information and photographic evidence was available to confirm the clinical diagnosis. In 12 patients the diagnosis was suggestive but lack of data prevented a definite diagnosis, and in 24 patients an alternative diagnosis was likely. Core manifestations of the syndrome are marked pre‐natal and severe post‐natal growth retardation, an unusual face (triangular shape, sparse hair, small mouth, pointed chin), dental anomalies (natal teeth; hypodontia), generalized lipodystrophy with localized fat masses, and—in some cases—progressive ataxia and tremor. It has been suggested that the syndrome might be caused by biallelic variants in POLR3A, identified by exome sequencing in a single patient only. Therefore, we compared the WRS phenotype with characteristics of conditions known to be caused by autosomal recessively inherited POLR3A mutations. There are major differences but there are also similarities in phenotype, which sustain the suggestion that the syndrome can be caused by disturbed POLR3A functioning.