The Renpenning syndrome spectrum: new clinical insights supported by 13 new PQBP1-mutated males

Clin Genet. 2011 Mar;79(3):225-35. doi: 10.1111/j.1399-0004.2010.01551.x. Epub 2010 Oct 18.

Abstract

Since the first reports of polyglutamine-binding protein 1 (PQBP1) mutations in Renpenning syndrome and related disorders, the spectrum of PQBP1-linked clinical manifestations has been outlined from rare published case reports. The phenotypic description is often obtained from medical archives, and therefore, heterogeneous. Moreover, some aspects such as brain imaging or cognitive and behavioral functioning are rarely described. In this study, 13 PQBP1-mutated French patients were subjected to a standardized clinical, cognitive and behavioral assessment. Physical measurements of their relatives were also collected. We report on a recognizable clinical and radiological phenotype. All patients presented with microcephaly, leanness and mild short stature, relative to familial measurements. Three new clinical features are described: upper back progressive muscular atrophy, metacarpophalangeal ankylosis of the thumb and velar dysfunction. The specific facial dysmorphic features included at least four of the following signs: long triangular face, large ridged nose, half-depilated eyebrows, dysplastic or protruding ears and rough slightly sparse hair. An over-aged appearance was noticed in elderly patients. Cortical gyrification was normal based on available magnetic brain imaging of six patients. PQBP1-linked microcephaly (or Renpenning syndrome) is an X-linked mental retardation syndrome, which has clinically recognizable features.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Brain / diagnostic imaging
  • Brain / pathology
  • Carrier Proteins / genetics*
  • Cerebral Palsy / complications
  • Cerebral Palsy / diagnostic imaging
  • Cerebral Palsy / genetics
  • Cerebral Palsy / pathology
  • Child
  • Child, Preschool
  • Cognition Disorders / etiology
  • DNA-Binding Proteins
  • Female
  • France
  • Genotype
  • Humans
  • Male
  • Mental Retardation, X-Linked / complications
  • Mental Retardation, X-Linked / diagnostic imaging
  • Mental Retardation, X-Linked / genetics
  • Mental Retardation, X-Linked / pathology
  • Mutation*
  • Nuclear Proteins / genetics*
  • Phenotype*
  • Pregnancy
  • Radiography
  • Young Adult

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • PQBP1 protein, human

Supplementary concepts

  • Renpenning syndrome 1