Wolf–Hirschhorn syndrome

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Wolf-Hirschhorn syndrome
Other namesChromosome deletion Dillan 4p syndrome, Pitt–Rogers–Danks syndrome (PRDS) or Pitt syndrome,[1][2]
Mia - whs.jpg
Young girl with Wolf-Hirschhorn syndrome
SpecialtyMedical genetics Edit this on Wikidata

Wolf–Hirschhorn syndrome (WHS), is a chromosomal deletion syndrome resulting from a partial deletion from the short arm of chromosome 4 (del(4p16.3)).[3] Features include a distinct craniofacial phenotype and intellectual disability.

Signs and symptoms[edit]

The most common characteristics include a distinct craniofacial phenotype (microcephaly, micrognathia, short philtrum, prominent glabella, ocular hypertelorism, dysplastic ears and periauricular tags), growth restriction, intellectual disability, muscle hypotonia, seizures, and congenital heart defects. Less common characteristics include hypospadias, colobomata of the iris, renal anomalies, and deafness.[4] Antibody deficiencies are also common, including common variable immunodeficiency and IgA deficiency. T-cell immunity is normal.[5]


Deletion of short arm of the chromosome 4 in a person with Wolf–Hirschhorn syndrome

Wolf–Hirschhorn syndrome is a microdeletion syndrome caused by a deletion within HSA band 4p16.3 of the short arm of chromosome 4, particularly in the region of WHSC1 and WHSC2.[6] About 87% of cases represent a de novo deletion, while about 13% are inherited from a parent with a chromosome translocation. In the cases of familial transmission, there is a 2 to 1 excess of maternal transmission. Of the de novo cases, 80% are paternally derived. Severity of symptoms and expressed phenotype differ based on the amount of genetic material deleted. The critical region for determining the phenotype is at 4p16.3 and can often be detected through genetic testing and fluorescence in situ hybridization (FISH). Genetic testing and genetic counseling is offered to affected families.



The minimum birth incidence has been calculated as 1 in 95,896.[7]


Wolf–Hirschhorn syndrome was first described in 1961 by Americans Herbert L. Cooper and Kurt Hirschhorn[8] and, thereafter, gained worldwide attention by publications by the German Ulrich Wolf, and Hirschhorn and their co-workers, specifically their articles in the German scientific magazine Humangenetik.[8][9]


  1. ^ Online Mendelian Inheritance in Man (OMIM) Wolf-Hirschhorn syndrome -194190
  2. ^ Rapini RP, Bolognia JL, Jorizzo JL (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp. 892, 894. ISBN 978-1-4160-2999-1.
  3. ^ Dufke A, Seidel J, Schöning M, Döbler-Neumann M, Kelbova C, Liehr T, Beensen V, Backsch C, Klein-Vogler U, Enders H (2000). "Microdeletion 4p16.3 in three unrelated patients with Wolf-Hirschhorn syndrome". Cytogenetics and Cell Genetics. 91 (1–4): 81–4. doi:10.1159/000056823. PMID 11173835.
  4. ^ Wieczorek D (September 2003). "Wolf-Hirschhorn syndrome" (PDF). Orphanet encyclopedia.
  5. ^ Hanley-Lopez J, Estabrooks LL, Stiehm R (July 1998). "Antibody deficiency in Wolf-Hirschhorn syndrome". The Journal of Pediatrics. 133 (1): 141–3. doi:10.1016/S0022-3476(98)70194-5. PMID 9672528.
  6. ^ Rauch A, Schellmoser S, Kraus C, Dörr HG, Trautmann U, Altherr MR, Pfeiffer RA, Reis A (April 2001). "First known microdeletion within the Wolf-Hirschhorn syndrome critical region refines genotype-phenotype correlation". American Journal of Medical Genetics. 99 (4): 338–42. doi:10.1002/ajmg.1203. PMID 11252005.
  7. ^ Shannon NL, Maltby EL, Rigby AS, Quarrell OW (October 2001). "An epidemiological study of Wolf-Hirschhorn syndrome: life expectancy and cause of mortality". Journal of Medical Genetics. 38 (10): 674–9. doi:10.1136/jmg.38.10.674. PMC 1734744. PMID 11584045.
  8. ^ a b Hirschhorn K, Cooper HL, Firschein IL (1961). "Deletion of short arms of chromosome 4-5 in a child with defects of midline fusion". Humangenetik. 1 (5): 479–82. doi:10.1007/bf00279124. PMID 5895684.
  9. ^ Wolf U, Reinwein H, Porsch R, Schröter R, Baitsch H (1965). "[Deficiency on the short arms of a chromosome No. 4]". Humangenetik (in German). 1 (5): 397–413. PMID 5868696.

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