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At a glance

This is a congenital medical condition characterized by a distinctive facial dysmorphism resembling in infancy to a “Greek warrior’s helmet appearance.” This is observed in patients with a broad bridge between the nose and the forehead, microcephaly, high forehead with prominent glabella, ocular hypertelorism, epicanthus, highly arched eyebrows, short philtrum, downturned mouth, micrognathia, and poorly formed ears with numerous pits/tags. Developmental delay and mental retardation of variable degree is present in all. Other features include severe muscle hypotonia, seizures, with prenatal onset. Cardiac malformations are observed in half of the cases and consist of septal defects, pulmonary valvular stenosis, and patent ductus arteriosus. Mental retardation is usually severe. Initial reports have suggested a predisposition to the development of malignant hyperthermia; however, subsequent reports have failed to confirm this association although there is no clear position about it. Antibody immunodeficiencies are also common, particularly for the IgA. T-cell immunity is otherwise normal. The disease is associated with a high mortality rate, approximately 30% within the first 2 years of life, with the most common causes of death being lower respiratory tract infections and congenital heart disease/cardiac failure.

Synonyms

Deletion 4p; Monosomy 4p; Dillan 4p Chromosome Deletion Syndrome; Dillan Syndrome.

N.B.: The ☞Pitt-Rogers-Danks Syndrome (Pitt Syndrome; PRDS) is known as a milder form of the ☞Wolf-Hirschhorn Syndrome and is often mistakenly diagnosed as a WHS (see “Other conditions to be considered” below).

History

This syndrome was first described in 1961 by two American physicians named Herbert L. Cooper and Kurt Hirschhorn (b. 1926). Dr Hirschhorn is an Austrian born American pediatrician, medical geneticist, and cytogeneticist who identified the chromosomal defects of the Wolf-Hirschhorn Syndrome (WHS). In 1995, he received the William Allan Award in human medical genetics. This medical condition subsequently gained worldwide attention following the publications of articles in the German scientific magazine Humangenetik by the Ulrich Wolf, Kurt Hirschhorn et al.

Incidence

Although the exact frequency remains unclear, it has been estimated at 1 in 95,896 live births in the general population. The prevalence is estimated at 1:50,000 live births. It has been suggested that there is a female to male ratio of 2:1; however, it is believed this to be wrong due to misdiagnosis in males.

Genetic inheritance

It is believed to be caused by a partial microdeletion of the short arm of 1 chromosome 4. This deletion is located within the HSA band of chromosome 4p16.3, particularly in the region of WHSC1 and WHSC2. It is reported that in 87% of cases, a de novo deletion can be identified whereas the remaining 13% are inherited from a parent with a chromosome translocation.

Pathophysiology

The critical zone for development of this disorder is located distal to the Huntington ...

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