Wolf–Hirschhorn syndrome
| Wolf–Hirschhorn syndrome | |
|---|---|
| Other names | Chromosome deletion Dillan 4p syndrome, Pitt–Rogers–Danks syndrome (PRDS), Pitt syndrome[1][2] |
 | |
| Young girl displaying characteristic facial features of Wolf–Hirschhorn syndrome | |
| Specialty | Medical genetics  |
Wolf–Hirschhorn syndrome (WHS) is a chromosomal deletion syndrome resulting from a partial deletion on 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. [4]
Less common characteristics include hypospadias, colobomata of the iris, renal anomalies, and deafness.[5] Antibody deficiencies are also common, including common variable immunodeficiency and IgA deficiency. T-cell immunity is normal.[6]
Genetics[edit]
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 WHSCR1 and WHSCR2.[7]
About 87% of cases represent a de novo deletion, while about 13% are inherited from a parent with a chromosome translocation.[4] 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.[citation needed]
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.[citation needed]
Diagnosis[edit]
Initial diagnosis is based on a distinct craniofacial phenotype after birth.[4] Diagnosis of WHS is confirmed by the detection of a deletion in the WHSCR. Chromosomal microarray and Cytogenetic analysis.D4S96 or D4Z1 chromosome band 4p16.3–specific probe (Wolf-Hirschhorn region, Vysis, Inc) is available for FISH study.[4]
Epidemiology[edit]
The minimum birth incidence has been estimated as 1 in 50,000.[4]
History[edit]
Wolf–Hirschhorn syndrome was first described in 1961 by the Austrian-born American pediatrician Kurt Hirschhorn and his colleagues.[8]
Thereafter, the syndrome gained worldwide attention after publications by the German geneticist Ulrich Wolf and his co-workers, specifically their articles in the German scientific magazine Humangenetik.[8][9]
References[edit]
- ^ Online Mendelian Inheritance in Man (OMIM): Wolf-Hirschhorn syndrome - 194190
- ^ Rapini RP, Bolognia JL, Jorizzo JL (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. pp. 892, 894. ISBN 978-1-4160-2999-1.
- ^ 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. S2CID 19641395.
- ^ a b c d e Paradowska-Stolarz AM (2014). "Wolf-Hirschhorn syndrome (WHS) - literature review on the features of the syndrome". Adv Clin Exp Med. 23 (3): 485–9. doi:10.17219/acem/24111. PMID 24979523.
- ^ Wieczorek D (September 2003). "Wolf-Hirschhorn syndrome" (PDF). Orphanet encyclopedia.
- ^ 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.
- ^ 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.
- ^ 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. S2CID 32805973.
- ^ 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.
External links[edit]
- https://www.ncbi.nlm.nih.gov/books/NBK1183/
- Wolf-Hirschhorn syndrome on Genetics Home Reference