Wolf-Hirschhorn syndrome (MIM.194190) is a chromosomal disorder characterized by retarded mental and physical growth, microcephaly, Greek helmet appearance of the facies, seizures/epilepsy. Closure defects of lip or palate, and cardiac septum defects occur in 30-50% of cases. Its cause is a deletion in the short arm of chromosome 4 (sporadic inheritance).

Synopsis

 systemic anomalies

• low birth weight
• marked growth retardation
• failure to thrive

 craniofacial anomalies

• low posterior hairline
• high-arched eyebrows
• sparse medial eyebrows
• microcephaly
• cranial asymmetry
• posterior midline scalp defects
• prominent glabella
• short philtrum
• micrognathia
• high forehead
• accessory tragus (preauricular tags)
• preauricular pits
• hearing loss
• narrow external auditory canals
• strabismus
• hypertelorism
• epicanthal folds
• exophthalmus
• ptosis
• Rieger anomaly
• nystagmus
• iris coloboma
• corectopia
• wide nasal bridge
• beaked nose
• cleft lip
• cleft palate
• downturned corners of mouth
• short upper lip
• hypodontia
• webbed neck

 cardiovascular anomalies

• atrial septal defect
• ventricular septal defect
• right ventricular hypoplasia

 sternal ossification center abnormalities
 fused ribs
 absence of gall bladder
 accessory spleen

 digestive anomalies

• intestinal malrotation
• gastroesophageal reflux

 congenital diaphragmatic hernia (#15108210#)

 genitourinary anomalies

• hypospadias
• cryptorchidism
• uterine agenesis (absent uterus)

 skeletal system anomalies

• delayed bone age
• sacral dimple
• sacral sinus
• scoliosis
• kyphosis
• fused vertebrae
• bifid vertebrae
• hip dislocation
• absence of pubic rami
• thin limbs
• radioulnar synostosis
• transverse palmar creases
• accessory proximal metacarpal ossification centers
• talipes equinovarus
• metatarsus adductus
• polydactyly
• posterior midline scalp defects
• sacral dimple
• hyperconvex fingernails

 cerebral anomalies

• cavum septum pellucidum
• absent septum pellucidum
• interventricular cysts
• hydrocephalus

 placental chorioangioma (#2062819#)
 jugular lymphatic obstruction sequence (#2062819#)

• cystic hygroma

Cytogenetics

 Partial deletion of short arm of chromosome 4 (4p-)

Etiology

 Locus: 4p16.1

References

 Bergemann AD, Cole F, Hirschhorn K. The etiology of Wolf-Hirschhorn syndrome. Trends Genet. 2005 Mar;21(3):188-95. PMID: #15734578#

 Fernandes BJ, Gardner HA, Bedard YC. The 4p- syndrome--an autopsy study. Hum Pathol. 1980 Nov;11(6):683-5. PMID: #7450742#