Wolf-Hirschhorn syndrome

[MIM 194 190, 602 618, 602 952, 604 407, 605 032, 605 830, 606 026]

Very rare: about 1/50,000. Sporadic. Affects girls two times more often than boys. Due in about 50-60% of cases to a de novo deletion (area WHSCR: WHSC1, NELFA LETM1, PIGG, CTBP1, FGFRL1 genes) at the level of 4p16.3 and in other cases to a unbalanced translocation combining a deletion in 4 p and a partial trisomy for another arm. A few cases are characterized by other complex rearrangements such as a chromosome 4 in ring shape. Pitt-Rogers-Danks syndrome (another form of 4p deletion) is often considered as a moderate variant of this syndrome.


Association of:


-        intrauterine growth retardation and postnatal failure to thrive as a consequence to feeding difficulties; hypotonia (especially of the limbs)

-        microcephaly with mental retardation, and often structural abnormalities of the brain (thin corpus callosum)

-        facial dysmorphism described as "Greek Warrior helmet": hypertelorism, prominent glabella,  large or broken nose, low  implanted ears (sometimes preauricular tags). bilateral cleft lip palate or cleft palate, micrognathia

-        congenital heart disease (50%): ASD, pulmonary stenosis, VSD, tetralogy of Fallot

-        convulsions (90-100%): onset in general in the first year; risk of status epilepticus; atypical absences in childhood: avoid carbamazepine which makes them worse 

-        hearing loss (> 40%) usually conductive

-        skeletal abnormalities (60-70%): clubfoot, hip dislocation, scoliosis (spinal malformation)

-        urogenital malformations (25 %): renal agenesis, dysplasia or hypoplasia; hypospadias and cryptorchidism (50% boys); absence of uterus

-        eye anomalies: retinal coloboma, nasolacrimal duct obstruction

-        immune disorders: deficiency in IgA and IgG2, responsible for recurrent respiratory infections

-        dental abnormalities: persistence of deciduous dentition, malformed teeth

-        gastro-esophageal reflux

-        increased risk of hepatic adenoma ?


Anesthetic implications:

epilepsy. Gastroesophageal reflux, sometimes disorders of swallowing. Risk of difficult intubation (it is better to use an endotracheal tube smaller than the size recommended for the age. Check kidney function and echocardiography. One reported case of metabolic acidosis with hyperthermia erroneously diagnosed as malignant hyperthermia.


References : 


Updated: March 2023