Roberts syndrome: a review of 100 cases and a new rating system for severity

Am J Med Genet. 1993 Nov 15;47(7):1104-23. doi: 10.1002/ajmg.1320470735.


Roberts syndrome (RS) is a rare genetic disorder characterized by pre- and postnatal growth retardation, limb defects, and craniofacial anomalies. Affected persons have varying degrees of malformations involving symmetric reduction in the number of digits, and length or presence of bones in the arms and legs. Craniofacial malformations involve hypertelorism, hypoplastic nasal alae, and a high incidence of cleft lip and palate. Familial and sporadic cases have been reported consistent with an autosomal recessive mode of inheritance. Mitotic cells from many individuals with RS display a characteristic cytogenetic phenomenon consisting of repulsion of heterochromatic regions near centromeres, particularly of chromosomes 1, 9, 16, and splaying of the short arms of the acrocentrics and of the distal Yq. Mitosis in RS cells is abnormal in metaphase duration and anaphase progression. Specifically, anaphase figures show a higher degree of chromosomes that are outlying, lagging, or prematurely advancing toward the poles compared to normal controls. RS cells have abnormal nuclear morphology and also show a higher frequency of micronucleation than normal cells, presumably as a result of the abnormal mitotic events during anaphase. Therefore, RS has been interpreted as a human mitotic mutation syndrome which leads to secondary developmental defects. This report reviews 100 cases of RS, summarizes the phenotypic, genetic, cytogenetic, and cell biology findings in Roberts syndrome, and introduces the RS Rating for quantitating severity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / pathology
  • Facial Bones / abnormalities
  • Female
  • Growth Disorders / genetics
  • Humans
  • Limb Deformities, Congenital
  • Male
  • Mitosis / genetics
  • Mutation
  • Pedigree
  • Phenotype
  • Skull / abnormalities
  • Syndrome