Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Wolf-Hirschhorn Syndrome (WHS; 4p-) [Q93.3]

OMIM number: 194190

Dr. med. Imma Rost

Scientific Background

The Wolf-Hirschhorn syndrome (WHS) is marked by a combination of characteristic physical features, congenital malformations, a severe developmental delay and short stature. Frequently, visual diagnosis is possible already in newborns or infants. Patients have wide-set eyes, a broad nasal bridge, highly arched eyebrows, downslanting palpebral fissures, divergent strabismus, frequently iris coloboma and cleft lip/palate, dysplastic ears, malformations of the heart and kidneys, hypospadia in boys. Approximately 80% of all patients suffer from seizures. WHS is caused by deletions varying in size of the terminal short arm of chromosome 4 (4p16.3). Smaller deletions (up to 3.5 mb) are considered to cause the milder form without malformations, moderate deletions (5-18 mb) the classic WHS and very large (22-25 mb) deletions a very severe form, without similarity to WHS. Deletions causing the classic WHS can frequently be detected during conventional chromosome analysis. Interstitial deletions with intact subtelomeric regions also occur. 85-90% of the deletions are de novo, the remaining percentage are due to chromosomal structural rearrangements, that may be present already in the parents in their balanced form. The frequency is 1:20,000 to 1:50,000.