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 (e.g., 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.
Lissencephaly Syndrome, Type I; MDLS.
It is undoubtedly a rare condition. 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 25-30% of patients with
classical lissencephaly have Miller-Dieker syndrome.
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).
Various possible causes of isolated lissencephaly
include viral infections, insufficient blood flow to the brain during fetal
development, and certain genetic factors.
Clinical picture and central nervous system imaging: smooth brain surface
(with or without pachygyria), thickened cortex, absent or hypoplastic
corpus callosum, small brainstem.
Postnatal failure to thrive with death before age 2 years. Microcephaly with
bitemporal narrowing, vertical ridging, and furrowing of the skin on the
forehead; up-slanted palpebral fissures; small nose with anteverted nostrils;
protuberant upper lip and micrognathia. May have cardiac defect (atrial
septal defect, ventricular septal defect, tetralogy of Fallot). Severe mental
deficiency with hypotonia progressing to spasticity and seizures. Dysphagia
and gastroesophageal reflux are common.
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.
Classic considerations for infants at
risk for difficult intubation and gastroesophageal reflux; adapt choice of
drugs and technique to the cardiac defect.
Antiepileptic treatment is usually
complex: possible induction of cytochrome P-450 enzymes. In presence of
cardiac anomalies, antibiotherapy must be considered.
Hard Syndrome: Characterized by type II lissencephaly in
association with retinal dysplasia, obstructive hydrocephalus, and agenesis
of the corpus callosum. Affected infants also typically have severe growth
failure, severe microcephaly, seizures, microphthalmia, and cataracts. Some
affected infants have an occipital encephalocele.
Neu-Laxova Syndrome: Rare genetic disorder in which
intrauterine growth retardation, polyhydramnios, and an unusually short
umbilical cord occur. Typically characterized by severe microcephaly, joint
contractures, generalized edema, and abnormalities of the brain and ...