J Med Genet 45:71-80 doi:10.1136/jmg.2007.052910
  • Original article

Genotype–phenotype correlation in 21 patients with Wolf–Hirschhorn syndrome using high resolution array comparative genome hybridisation (CGH)

  1. N M C Maas1,
  2. G Van Buggenhout1,
  3. F Hannes1,
  4. B Thienpont1,
  5. D Sanlaville2,
  6. K Kok3,
  7. A Midro4,
  8. J Andrieux5,
  9. B-M Anderlid6,
  10. J Schoumans6,
  11. R Hordijk3,
  12. K Devriendt1,
  13. J-P Fryns1,
  14. J R Vermeesch1
  1. 1
    Center for Human Genetics, University Hospital, Catholic University of Leuven, Leuven, Belgium
  2. 2
    Department of Genetics, Hôpital Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France
  3. 3
    Department of Medical Genetics, University Medical Center Groningen, Groningen, The Netherlands
  4. 4
    Department of Clinical Genetics of the Medical University Białystok, Poland
  5. 5
    St Vincent Hospital, Lille, France
  6. 6
    Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden
  1. J R Vermeesch, Center for Human Genetics, Herestraat 49, 3000 Leuven, Belgium; Joris.Vermeesch{at}
  • Received 6 July 2007
  • Revised 21 August 2007
  • Accepted 23 August 2007
  • Published Online First 14 September 2007


Background: The Wolf-Hirschhorn syndrome (WHS) is usually caused by terminal deletions of the short arm of chromosome 4 and is phenotypically defined by growth and mental retardation, seizures, and specific craniofacial manifestations. Large variation is observed in phenotypic expression of these features. In order to compare the phenotype with the genotype, we localised the breakpoints of the 4pter aberrations using a chromosome 4 specific tiling BAC/PAC array.

Methods: In total, DNA from 21 patients was analysed, of which 8 had a cytogenetic visible and 13 a submicroscopic deletion.

Results and conclusion: In addition to classical terminal deletions sized between 1.9 and 30 Mb, we observed the smallest terminal deletion (1.4 Mb) ever reported in a patient with mild WHS stigmata. In addition, we identified and mapped interstitial deletions in four patients. This study positions the genes causing microcephaly, intrauterine and postnatal growth retardation between 0.3 and 1.4 Mb and further refines the regions causing congenital heart disease, cleft lip and/or palate, oligodontia, and hypospadias.


  • Competing interests: None declared.

  • Informed consent was obtained from all patients’ legal guardians for publication of the images.