Miller
Dieker SyndromeMiller Dieker syndrome was first thought to be inherited
in an autosomal recessive pattern, however in the 1990’s it was detected that
there is also autosomal recessive inheritance, but that both of these types of
inheritances occur only in 20% of cases. 80% of the cases develop spontaneously (by de novo
deletion of the short arm of chromosome 17, see more details under Ref.1 below).
90% of cases have a loss of the LIS1 gene, which leads to a malformation of the
brain; however, there is a spectrum of Miller Dieker syndrome where many other
adjacent (contiguous) genes are lost as well, which adds to the high mortality
rate of these babies depending on what organs are affected. Signs
and symptoms The major genetic abnormality in this syndrome is
the lissencephaly, which is the malformation of the outer layer of the brain cortex.
Here is an MRI
image of such a brain malformation (type I lissencephaly) that shows a
lack of surface structure (gyri) and an increase of the hollow space inside the
brain. Surviving individuals have severe mental retardation. They have low
set ears, severe vision problems, a high forehead and a small mouth with
a wide upper lip. Initially there is a normal head size at birth, but by one year
they have a much smaller than normal head circumference (microcephaly), because
of poor brain growth. Convulsions (seizures) happen frequently within the first
few weeks to months. Feeding is extremely poor and there is a constant danger
of aspiration of baby food as the normal swallowing and cough reflexes are poorly
developed. Aspiration pneumonia and infections are common leading to a high mortality
in the first year. There can be other genetic abnormalities affecting the heart
and kidneys. Cleft palates are also common leading to even worse feeding problems.
Diagnosis A special technique called
FISH
(fluorescent in situ hybridization) can be used on cultured blood lymphocytes
to look for the genetic deletion on chromosome
17 at the 17p13.3 location. CT or MRI scans will show the brain abnormalities
mentioned above. Prognosis Most babies with Miller
Dieker Syndrome die in the first three months of life and most infants are dead
from complications of seizures, aspiration pneumonia etc. within two years of
age. Occasionally individuals will live for several years.
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