Wolf-Hirschorn Syndrome

Synonyms: chromosome 4p deletion syndrome, 4p- syndrome, monosomy 4p syndrome.¹

Wolf-Hirschorn syndrome (WHS) is a well-characterized chromosomal disorder that occurs due to partial deletion of the short arm of chromosome 4 (4p-).²

• The incidence is estimated at 1 in 50,000 births.³
• Female to male ratio is 2:1.

• Severe growth retardation, microcephaly, hydrocephalus, corpus callosum agenesis.
• Severe mental retardation, severe limitation of comprehension and speech, seizures, ataxic gait, hypotonia, muscle hypertrophy.
• Microcephaly, a distinct "Greek warrior helmet" face with characteristic broad beaked nose, high frontal hairline and frontal bossing.
• Contracture of hands, wrists, and feet.
• Poor development of secondary sexual characteristics.
• Closure defects (cleft lip or palate, coloboma of the eye, and cardiac septal defects).
• Hypoplasia of kidneys and genital tract. Diaphragmatic hernia with secondary lung hypoplasia.
• Immunodeficiency.

• Similar multiple congenital anomalies and mental retardation syndromes, including Proximal 4p syndrome and Seckel syndrome.

• Prenatal diagnosis: anomaly ultrasound scan will suggest distinct physical characteristics and should be followed by karyotyping. Chromosomal analysis from amniocentesis or chorionic villus sampling. Umbilical blood sampling for rapid fetal karyotyping.
• Immunoglobulin and T cell numbers and function for likely immunodeficiency.
• EEG: characterized by distinctive seizure and EEG patterns.²
• Echocardiography: possible atrial septal defect or ventricular septal defect.
• Imaging of the urinary tract.
• MRI and CT scans for underlying brain pathology, e.g. corpus callosum agenesis and enlarged ventricles.

• No treatment exists for the underlying disorder and management is supportive.
• Seizures may be difficult to control.
• The management plan will require a multidisciplinary team approach and depend on the range of associated developmental,physical and behavioural problems.

• Frequently results in stillbirth or death within the first year.
• If patients survive beyond infancy, they have slow but constant progress in terms of development.
• About one-third die within the first two years of life, usually due to a heart defect, aspiration pneumonia, other severe infection or resulting from a seizure.
• Recurrence risk is negligible unless a parent is a translocation carrier.

• Genetic counselling.