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Wolf-Hirschhorn syndrome

Saturday 5 January 2008

Patients with deletions of distal 4p have the characteristic features of Wolf-Hirschhorn syndrome (WHS).

Wolf-Hirschhorn syndrome, also known as deletion 4p and 4p- syndrome was first described in 1961 by the Americans Herbert L. Cooper and Kurt Hirschhorn, 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’.

It is a characteristic phenotype resulting from a partial deletion of chromosomal material of the short arm of chromosome 4.


- profound mental retardation
- microcephaly
- seizures
- poor muscle tone
- cleft lip and/or cleft palate
- strabismus
- hypertelorism
- bilateral microphthalmia (18551766)
- orbital cysts (18551766)
- posterior intraorbital coloboma cyst (15030910)

- down-turned "fishlike" mouth
- short upper lip and philtrum
- small chin
- ear tags or pits
- cranial asymmetry
- heart defects
- hypospadias
- scoliosis, ptosis
- fused teeth
- hearing loss
- delayed bone age
- low hairline with webbed neck
- renal anomalies
- multiple hemangiomas (18076104)
- congenital diaphragmatic hernia (16903248)
- cutaneous T-cell lymphoma (15103723)


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. The symptoms and phenotype do not differ based on the size of the deletion.

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.


- Pardo S, Blitman N, Han B, Cohen N, Edelmann L, Hirschhorn K. Multiple hemangiomas in a patient with a t(3q;4p) translocation: an infrequent association with Wolf-Hirschhorn syndrome. Am J Med Genet A. 2008 Jan 15;146(2):219-24. PMID: 18076104