Lissencephaly and facial dysmorphism: is it Miller–Dieker syndrome?

Abstract

An 8-month-old girl presented with developmental delay and flexor jerks for the past 2 months. Examination showed unusual facial characteristics, such as bitemporal hollowing, prominent upper lip, high arched palate and retrognathia (Fig. 1a), microcephaly, spasticity, brisk muscle stretch reflexes and flexor-infantile spasms. She had no neck-control, visual following or social smile. Magnetic resonance imaging showed lissencephaly (Fig. 1b). Genetic analysis confirmed deletion of the 17p13.3 chromosome. Electroencephalograph showed hypsarrhythmia. Adrenocoticotropic hormone or Corticotropin therapy, rehabilitation and antenatal diagnosis for future pregnancies was offered to the parents. Lissencephaly can occur either as a result of a contiguous gene deletion disorder known as Miller–Dieker syndrome or as an isolated form known as isolated lissencephaly sequence (i.e. without facial dysmorphism or other abnormalities, such as abnormal genitalia or cerebellar hypoplasia) as a result of a single gene mutation in the LIS1 or DCX gene. Miller–Dieker syndrome, as a result of chromosome-band 17p13.3 deletions, is a multiple malformation syndrome characterized by severe lissencephaly (Dobyns’ grade 2; diffuse agyria with a few shallow sulci); characteristic facial features such as high, prominent forehead, bitemporal hollowing, short nose with upturned nares, protuberant upper lip and small jaw; and severe psychomotor impairment. Early-infantile seizures, especially infantile spasms with evolution into Lennox–Gastaut syndrome occur in the majority of patients. Genetic confirmation is crucial for prognosis and prenatal diagnosis.