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Am J Med Genet A. 2017 Jul;173(7):1763-1772. doi: 10.1002/ajmg.a.38246. Epub 2017 Apr 26.

Wiedemann-Rautenstrauch syndrome: A phenotype analysis.

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Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy.
Unidade de Genética do Instituto da Criança, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Department of Clinical Genetics, Guy's Hospital, London, United Kingdom.
Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, Rome, Italy.
Institute of Human Genetics, University Medical Center Göttingen, Göttingen, Germany.
Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.


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.


4H syndrome; POLR3A; POLR3B; Wiedemann-Rautenstrauch syndrome; autosomal recessive; cerebellar hypoplasia-endosteal sclerosis; lipodystrophy


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