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GENATLAS PHENOTYPE
last update : 21-12-2015
Symbol WHS
Location 4p16.3
Name Wolf-Hirschhorn syndrome
Other name(s) monosomy 4p, del 4p, 4p-
Corresponding gene WHSC1 , WHSC2 , LETM1 , SLBP
Other symbol(s) DEL4P, WHCR, WHSCR, PRDS
Main clinical features
  • classical form
  • characteristic facial features : 'Greek warrior helmet appearance' of the nose, microcephaly, hypertelorism, highly arched eyebrows, short philtrum, downturned mouth, micrognathia, poorly formed ears with pits/tags, dental abnormalities (delayed eruption, fusion, agenesis)
  • marked IUGR/postnatal growth retardation, hypotonia with muscles under development, thin habitus, usually severe mental retardation, seizures (50-100%), midline defects [cleft lip or palate, coloboma of the eye], skeletal anomalies, congenital heart defects, hearing loss, urinary tract malformation, structural brain abnormalities
  • cellular defects associated with WHS, including delayed S-phase progression and reduced DNA synthesis, impaired histone deposition, altered higher order chromatin structure and enhanced sensitivity to DNA damage (PMID: 22328085))
  • Genetic determination chromosomal
    Prevalence frequency estimated as 1/50,000-1/20,000 births, with a female predilection of 2:1.
    Related entries see WHSCR for small or cryptic deletions
    Function/system disorder multisystem/generalized
    mental retardation
    Type MCA/MR
    Gene product
    Name WHSC1 might function as a chromatin remodelling enzyme
    Mechanism(s)
    Gene mutationChromosome rearrangementEffectComments
      deletion haploinsufficiency large 4p deletion of several megabases usually detected by conventional cytogenetics
      translocation haploinsufficiency recurrent t(4;8)(p16;p23)translocation mediated by olfactory receptor-gene clusters, unbalanced form
      translocation   aCGH studies indicates a high prevalence of unbalanced translocations as high as 45 percent
    Remark(s) contiguous gene syndrome with an unknown number of genes contributing to the phenotype; no single gene deletions or intragenic mutations have been shown to confer the full WHS phenotype
    Genotype/Phenotype correlations microdeletions detected by FISH (WHCR probe) have a milder phenotype (see WHSCR); three different categories of the WHS phenotype were defined, generally correlating with the extent of the 4p deletion: small deletions not exceeding 3.5 Mb, that are usually associated with a mild phenotype, lacking major malformations, large deletions, averaging between 5 and 18 Mb, causing the widely recognizable WHS phenotype, and very large deletions exceeding 2225Mb causing a severe phenotype, that can hardly be defined as typical WHS