The disease was first described by Hirschhorn and Cooper in 1961, the second case was published in 1965 by Wolf et al. Wolf-Hirschhorn syndrome (WHS) is a congenital disorder with specific clinical features mostly caused by de novo microdeletion of the distal short arm of chromosome 4 (del 4p 16.3) among Wolf-Hirschhorn candidate gene (WHSC1 and WHSC2).

Only 10 % are caused by translocation [2,3]. The prevalence of the WHS is estimated at 1:50 000 births with a 2:1 female to male ratio. The severity of the phenotypic manifestation of WHS correlates with the amount of chromosomal deletion. The mortality rate is about 30% within the first two years of life mainly due to aspirations leading to pulmonary infections, epileptic seizures or cardiac failure. The seizures are often hard to control, but tend to decline with age. The typical clinical features can vary [1,12]. More than 75% of patients have typical facial feature of “Greek warrior helmet” appearance (wide bridge of nose, high forehead), microcephaly, low set ears, growth retardation with prenatal onset, muscular hypotonia, failure to thrive, seizures, febrile convulsions, EEG abnormalities, mental disability of variable degree. 50-75% of patients have skeletal abnormalities as scoliosis, congenital hip dislocation or clump feet, craniofacial asymmetry, microstomia, abnormal teeth, IgA or IgG2 deficiency. 25-50% of patients have hearing loss, heart defect (mostly atrial or ventricular septal defect), eye or optic nerve anomalies, cleft lip and cleft palate, genitourinary tract anomalies, structural brain anomalies and stereotypies. Congenital heart defects usually are not complex. Less than 25% of patients have anomalies concerning liver, gallbladder, gut, diaphragm, esophagus, lung and aorta, malignancies of liver or hematopoietic system.