Miller-Dieker Lissencephaly Syndrome

At a glance

Malformation of the cerebral cortex with abnormal facies. Classic lissencephaly, also known as lissencephaly type I, is a brain malformation that may occur as an isolated abnormality (isolated lissencephaly sequence) or in association with certain underlying syndromes (eg, Miller-Dieker Syndrome, Norman-Roberts Syndrome). The condition is characterized by agyria or pachygyria of the gyri of the cerebral cortex, causing the brain’s surface to appear unusually smooth. In infants with classic lissencephaly, microcephaly is usually present. Other clinical features include seizures, severe or profound mental retardation, feeding difficulties, growth retardation, and impaired motor functions.

Synonyms

Lissencephaly Syndrome, Type I; MDLS.

Classification

This medical condition is part of a spectrum of disease that consists of five types of ☞lissencephaly.

Incidence

It is undoubtedly a rare condition. The exact incidence remains unknown. In 1991, it was reported in the only published epidemiological study performed in the Dutch population that the prevalence was 11.7 per million live births. Since then, the larger use of MRI diagnosis has most certainly contributed to make the incidence and prevalence higher. It is suggested that 25 to 30% of patients with classical lissencephaly have Miller-Dieker Syndrome.

Genetic inheritance

Usually sporadic cases with no familial inheritance; in most cases, changes (mutations) of at least two different genes have been implicated in isolated lissencephaly: a gene located on chromosome 17 (known as LIS1) and a gene located on the X chromosome (deletions or mutations of gene LIS1 on chromosome 17 p13.3).

Pathophysiology

Various possible causes of isolated lissencephaly include viral infections, insufficient blood flow to the brain during fetal development, and certain genetic factors.

Diagnosis

Clinical picture and central nervous system imaging: smooth brain surface (with or without pachygyria), thickened cortex, absent or hypoplastic corpus callosum, small brain stem.

Clinical aspects

Postnatal failure to thrive leading to death before age 2 years. It is characterized by microcephaly with bitemporal narrowing, vertical ridging, and furrowing of the skin on the forehead. Other features include up-slanted palpebral fissures, small nose with anteverted nostrils, protuberant upper lip, and micrognathia. Affected patients may have cardiac defect (atrial septal defect, ventricular septal defect, tetralogy of Fallot) and cardiomyopathy leading to sudden death. Severe mental deficiency with hypotonia is progressing to spasticity and severe generalized seizures. Dysphagia and gastroesophageal reflux are common.

Precautions before anesthesia

Check for chronic aspiration pneumonia (radiography), presence of a cardiac defect, and possible undernutrition; antiepileptic and antireflux treatment should be continued until the morning of anesthesia.

Anesthetic considerations

Classic considerations for infants at risk for difficult intubation and gastroesophageal ...