| Wolf-Hirschhorn syndrome | |
|---|---|
| Classification and external resources | |
A neonate with Wolf-hirschhorn syndrome |
|
| ICD-10 | Q93.3 |
| ICD-9 | 758.3 |
| OMIM | 194190 |
| DiseasesDB | 32279 |
| eMedicine | ped/2446 |
Wolf–Hirschhorn syndrome (WHS), also known as chromosome deletion 4p syndrome, Pitt-Rogers-Danks syndrome (PRDS) or Pitt syndrome,[1][2] was first described in 1961 by Americans Herbert L. Cooper and Kurt Hirschhorn[3] 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.[4][5] It is a characteristic phenotype resulting from a partial deletion of chromosomal material of the short arm of chromosome 4 (del(4p16.3)).
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The most common characteristics include a distinct craniofacial phenotype (microcephaly, micrognathia, short philtrum, prominent glabella, ocular hypertelorism, dysplastic ears and periauricular tags), growth and mental retardation, muscle hypotonia, seizures, and congenital heart defects. Less common characteristics include hypospadias, colobomata of the iris, renal anomalies, and deafness.[6] Antibody deficiencies are also common, including common variable immunodeficiency and IgA deficiency. T-cell immunity is normal.[7]
Wolf-Hirshhorn syndrome is caused by a partial deletion of the short arm of chromosome 4, particularly in the region of WHSC1 and WHSC2. 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 translocation, 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 fluorescent in situ hybridization (FISH). Genetic testing and genetic counseling is offered to affected families.