Lissencephaly syndrome
Discussion and General Information:
Heredity/Genetic:
Lissencephaly I - Gene map locus 17p13.3 (ILS, LIS1, Lissencephaly
sequence,
isolated; Lissencephaly, classic; SBH; SCLH; Subcortical band
heterotopia;
Subcortical laminar heterotopia; MDLS)
Lissencephaly, X-linked - Gene map locus Xq22.3-q23 (Double cortex
syndrome;
LISX; Lissencephaly and agenesis of corpus callosum; Subcortical band
heterotopia, X-linked; Subcortical laminar heterotopia, X-linked)
--------------
Lissencephaly is a set of rare brain disorders and you will probably find that very few people have heard of it. Lissencephaly is used as an 'umbrella' term to describe a range of disorders where the whole or parts of the surface of the brain appear smooth.
The range of disorders include:
You may have
also been told that your child may
be diagnosed with either agyria or pachygyria - these terms are
generally used
to describe the degree of brain smoothness and are often included in
some of the
diagnoses above.
The word lissencephaly is derived from the Greek "lissos" meaning
smooth and "encephalos" meaning brain. The human brain
normally
has a convoluted surface. In Lissencephaly these convolutions are
completely or
partially absent from the brain, or areas of it, have a smooth
appearance. The
convolutions are also called "gyri" and their absence is known as
"agyria" (without gyri). In some cases convolutions are present, but
thicker and reduced in number and you may hear the term
"pachygyria"
(broad gyri) being used. The diagnosis is usually made with the help of
a CT
Scan or MRI Scan of the brain.
* neither SCH or PMG are strictly lissencephaly, but are often included
because
of the similarity in brain scan appearance (1)
Types: While there are several lissencephaly syndromes, these all fall under the category of either Type I or Type II. Type I lissencephaly occurs in isolated lissencephaly sequence, in Miller-Dieker syndrome and in a very rare condition called Norman-Roberts syndrome. Type II occurs in Fukuyama syndrome and Walker-Warburg syndrome. Fukuyama syndrome is usually known as Fukuyama congenital muscular dystropy. (2)
Causes: There are probably several causes of lissencephaly. It can be caused by injury to the fetus during development in the womb such as infections, trauma, insufficient blood flow to the brain. Genetic mutation is another cause. There have been two genes found to be associated with lissencephaly. One is on Chromosome 17, named LIS1. The other is on the X chromosome (named XLIS or Doublecortin).
Symptoms and/or complications: Mental retardation, developmental delays, eye abnormalities, muscular dystrophy (difficulty controlling his/her muscles or stiffness or spasticity of arms and legs); seizures; generalized edema and/or lymphedema
Diagnosis: Initially may be suspected due to developmental delays, spasms, and/or seizures. Diganostic imaging through use of MRI or CT can confirm the diagnosis.
Treatment: Treatment depends on the type of lissencephaly, severity and developmental delays or abnormalities. If there are seizures, treament will be needed for that, there may be a need for a feeding tube, a shunt if there is hydrocephalus,
Prognosis: There is no set prognosis, rather the prognosis depends totaly on the degree of brain malformation and the severity of the lissencephaly.
Lissencephaly is classified as a Cephalic Disorder.
Cephalic disorders are congenital conditions that stem from damage to, or abnormal development of, the budding nervous system. Cephalic is a term that means "head" or "head end of the body." Congenital means the disorder is present at, and usually before, birth. Although there are many congenital developmental disorders, this fact sheet briefly describes only cephalic conditions.
Cephalic disorders are not necessarily caused by a single factor but may be influenced by hereditary or genetic conditions or by environmental exposures during pregnancy such as medication taken by the mother, maternal infection, or exposure to radiation. Some cephalic disorders occur when the cranial sutures (the fibrous joints that connect the bones of the skull) join prematurely. Most cephalic disorders are caused by a disturbance that occurs very early in the development of the fetal nervous system.(3)
May 30, 2008
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Lissencephaly syndrome
| GeneTests, Links | |
| MILLER-DIEKER LISSENCEPHALY SYNDROME; MDLS | |
Alternative titles; symbols
MDSA number sign
(#) is used with this entry because the Miller-Dieker
lissencephaly syndrome appears to be caused by deletion of several
genes on 17p.
Deletion of or mutation in the LIS1 gene (601545)
appears to cause the lissencephaly because point mutations have been
identified
in the disorder isolated lissencephaly sequence (ILS; see 607432).
On the other hand, facial dysmorphism and other anomalies in
Miller-Dieker
patients appear to be the consequence of deletion of additional genes
distal to
LIS1. Toyo-oka
et al. (2003) presented evidence that the gene whose deletion
is responsible
for the greater severity of Miller-Dieker syndrome compared to isolated
lissencephaly is the gene encoding 14-3-3-epsilon (YWHAE; 605066).
(The number 247200
was assigned to this entry when it was first created between the fourth
(1975)
and eighth (1978) editions of Mendelian Inheritance in Man, on the
presumption
that the disorder was autosomal recessive. It turns out that both
isolated
lissencephaly sequence and the Miller-Dieker syndrome are due to
haploinsufficiency of one or more genes on 17p; they are autosomal
dominant
disorders.)
Miller-Dieker lissencephaly syndrome is a chromosomal microdeletion disorder characterized by microcephaly and a thickened cortex with 4 rather than 6 layers. Lissencephaly means 'smooth brain,' i.e., brain without convolutions or gyri.
Miller
(1963) described this condition in a brother and sister who
were the fifth
and sixth children of unrelated parents. The features were
microcephaly, small
mandible, bizarre facies, failure to thrive, retarded motor
development,
dysphagia, decorticate and decerebrate postures, and death at 3 and 4
months,
respectively. Autopsy showed anomalies of the brain, kidney, heart, and
gastrointestinal tract. The brains were smooth with large ventricles
and a
histologic architecture more like normal fetal brain of 3 to 4 months'
gestation.
Dieker
et al.
(1969) described 2 affected brothers and an affected female
maternal first
cousin. They also emphasized that this should be termed the
lissencephaly
syndrome because malformations of the heart, kidneys, and other organs,
as well
as polydactyly and unusual facial appearance, are associated.
Reznik
and
Alberca-Serrano (1964) described 2 brothers with congenital
hypertelorism,
mental defect, intractable epilepsy, progressive spastic paraplegia,
and death
at ages 19 and 9 years. The mother showed hypertelorism and short-lived
epileptiform attacks. Autopsy showed lissencephaly with massive
neuronal
heterotopia, and large ventricular cavities of embryonic type. (The
findings in
the mother made X-linked recessive inheritance a possibility.) The
patients of Reznik
and Alberca-Serrano (1964) may have suffered from a disorder
distinct from
that described by Miller
(1963) and Dieker
et al. (1969). All patients with the Miller-Dieker syndrome
are severely
retarded. None learned to speak. They may walk by 3 to 5 years but
spastic
diplegia with spastic gait is evident. As in other forms of stationary
forebrain
developmental anomalies, decerebrate posturing with head retraction
emerges in
the first year of life. In the case of Norman
et al. (1976), 3 sibs were affected and the parents were
third cousins.
Dobyns
et
al. (1983) stated that the most characteristic finding on
computerized
tomography is complete failure of opercularization of the frontal and
temporal
lobes, and that this most likely accounts for bitemporal hollowing.
(Opercularization
is formation of the parts of the lobes that cover part of the insula.)
The form
of lissencephaly in the Miller-Dieker syndrome was designated classical
or type
I lissencephaly by Dobyns
et al. (1984). It is characterized by microcephaly and a
thickened cortex
with 4 rather than 6 layers. (Type II lissencephaly has associated
obstructive
hydrocephalus and severe brain malformations. It is a major
manifestation of the
HARD plus/minus-E syndrome (236670).
The Walker-Warburg syndrome (236670)
is the most frequent form of type II lissencephaly (Dobyns
et al., 1988). A third form occurs in the Neu-Laxova syndrome
(256520).
Dobyns et al.
(1984) suggested the designation Norman-Roberts syndrome (see
257320)
for the disorder associated with type I lissencephaly but distinct from
the
Miller-Dieker syndrome. A low, sloped forehead and prominent nasal
bridge are
distinctive to this condition and chromosomes are normal.)
Bordarier et al. (1986) pointed out that agyria was considered a rare malformation until the recent progress in neuroradiology.
Selypes
and
Laszlo (1988) described the Miller-Dieker syndrome in a
12-year-old boy with
a de novo terminal deletion of 17p13. He had growth retardation,
microcephaly,
ptosis of the left eyelid, low-set ears, prominent philtrum, thin upper
lip,
clinodactyly of the fifth fingers, and atrial septal defect.
Lissencephaly was
demonstrated by computerized tomography. MDS is a severe neuronal
migration
abnormality.
Dobyns
et
al. (1988) found the most consistent features of the facies
in MDLS to be
bitemporal hollowing, prominent forehead, short nose with upturned
nares,
prominent upper lip, thin vermilion border of the upper lip, and small
jaw.
Agenesis of the corpus callosum was demonstrated by computerized
tomography in
about 90% of cases. The cerebellum was normal in all. Striking midline
calcifications were found in most patients with visible chromosomal
change.
Allanson
et
al. (1998) reported pattern profiles on 5 children with MDLS
and 25 children
and adolescents with isolated lissencephaly sequence. The patients with
ILS at
all ages showed reduced head circumference and a wide and flat face
with a broad
nose and widely spaced eyes. In the age group of 6 months to 4 years of
age,
there was similarity between the pattern profiles of ILS and MDLS, with
a
correlation coefficient of 0.812 (p less than 0.001). In MDLS there are
a few
distinguishing features, including brachycephaly, a slightly wider
face, and a
considerably shorter nose. Allanson
et al. (1998) concluded that given the striking similarity of
the pattern
profiles, the principal diagnostic discriminators are qualitative
features,
specifically the tall, furrowed forehead and the long, broad thickened
upper lip
in MDLS. They also concluded that their observations were consistent
with the
concept of additional gene(s) telomeric to LIS1 contributing to the
facial
phenotype of MDLS.
Dobyns
et
al. (1983) found a ring chromosome 17 in 1 patient and were
prompted to
study 2 other cases. They found partial monosomy of 17p13 in one of
these. A
review of the literature uncovered abnormality of 17p in 5 other
patients in 3
families. Sharief
et al. (1991) reported a case of MDS associated with ring
chromosome 17.
Ledbetter
(1983) studied the parents of the patients reported by Miller
(1963), Dieker
et al. (1969), and Norman
et al. (1976). The father of Miller's sibs had a 15q;17p
translocation; the
father of Dieker's patients 1 and 3 had a 12q;17p translocation and
both parents
of Norman's patient had normal karyotypes. An autosomal recessive form
of
lissencephaly is suggested also by the parental consanguinity in
Norman's case.
Stratton
et
al. (1984) further narrowed the monosomy to 17p13.3. They
also reported
prenatal diagnosis. In a patient with MDS and no cytogenetically
detectable
deletion, vanTuinen
and Ledbetter (1987) found evidence of deletion by use of a
DNA marker
located at 17p13.3. Greenberg
et al. (1986) described a family in which the mother had a
pericentric
inversion of chromosome 17 and 2 of her children had MDS. One of them
was shown
to carry a recombinant 17 consisting of dup(17q) and del(17p). The
patient
described by Selypes
and Laszlo (1988) had a de novo terminal deletion of 17p13.
Bordarier et al. (1986) reported anatomoclinical observations on a case of partial deletion of 17p. Golgi stains showed many inverted pyramidal cells in the superficial part of the cortex.
Dhellemmes
et
al. (1988) found a microdeletion of 17p in 1 of 12 cases with
lissencephaly.
They subscribed to the 4-way classification of lissencephalies proposed
by Dobyns
et al. (1984): the Miller-Dieker syndrome with abnormality of
chromosome 17;
the Miller-Dieker syndrome without evident abnormality of chromosome
17; a
disorder with manifestations unlike those of the Miller-Dieker syndrome
but with
familial occurrence and normal chromosomes (Norman-Roberts syndrome);
and a form
without characteristic facial dysmorphism and without familial
occurrence. In
the study of Dhellemmes
et al. (1988), 1 patient was in category 1 and the other 11
were in category
4.
Dobyns
et al.
(1991) reviewed the results of their clinical, cytogenetic,
and molecular
studies in 27 patients with MDS from 25 families. All had severe type I
lissencephaly with grossly normal cerebellum and a distinctive facial
appearance
consisting of prominent forehead, bitemporal hollowing, short nose with
upturned
nares, protuberant upper lip, thin vermilion border, and small jaw.
Chromosome
analysis showed deletion of band 17p13 in 14 of 25 MDS probands.
Studies using
probes from the 17p13.3 region detected deletions in 19 of 25 probands
tested,
including 7 in whom chromosome analysis was normal. When the
cytogenetic and
molecular data were combined, deletions were detected in 21 of 25
probands. Of
the 11 patients in whom parental origin of the de novo deletion was
determined,
paternal origin was demonstrated in 7 and maternal origin in 4.
De Rijk-van Andel et al. (1991) identified a submicroscopic deletion of 2 DNA markers located at 17p13 in a patient with isolated grade 3 lissencephaly. The findings suggested that MDS and isolated lissencephaly have a common etiology.
About 90% of
MDS patients have visible or submicroscopic deletions of
17p13.3; Ledbetter
et al. (1992) investigated the possibility that some patients
with 'isolated
lissencephaly sequence' (ILS) had smaller deletions in that chromosomal
region.
Their studies uncovered 6 submicroscopic deletions in 45 ILS patients
with gyral
abnormalities ranging from complete agyria to mixed agyria/pachygyria
and
complete pachygyria. In situ hybridization proved to be the most rapid
and
sensitive method of deletion detection. The centromeric boundary of
these
deletions overlapped that of MDS patients, while the telomeric boundary
for 4 of
them was proximal to that of MDS.
Oostra
et
al. (1991) studied 5 patients with MDS, 17 patients with
isolated
lissencephaly sequence, 1 patient with an unclassified form of
lissencephaly,
and 9 patients with an atypical cortical dysplasia. All patients had
normal
chromosomes except for a deletion of 17p13.3 in 1 of the 5 MDS
patients. The 5
MDS patients showed deletion of markers YNZ22.1 and YNH37.3. Dobyns
et al. (1993) reviewed the clinical phenotype, pathologic
changes, and
results of cytogenetic and molecular genetic studies in 90 probands
with
lissencephaly, with emphasis on patients with the classic form (type
I).
A cryptic
translocation in one of the parents of MDS patients had been found
using fluorescence in situ hybridization (FISH) (Kuwano
et al., 1991). Masuno
et al. (1995) described a patient with MDS and a maternal
cryptic
translocation. Kingston
et al. (1996) described a boy who, in addition to
lissencephaly and facial
features of MDS, had rhizomelic shortening of the limbs, cleft palate,
hypospadias, and sacral tail. Banded chromosome analysis did not reveal
any
abnormality of chromosome 17. FISH studies with the alpha satellite
probe D17Z1
and 3 overlapping cosmids from the MDS critical region showed that his
mother
and grandmother carried a balanced inv(17)(p13.3q25.1). The proband's
karyotype
was 46,XY,rec(17),dup q,inv(17)(p13.3q25.1)mat. Additional
manifestations in the
proband were due to distal 17q trisomy. Masuno
et al. (1995) and Kingston
et al. (1996) stated that FISH analysis is crucial to exclude
subtle
rearrangements in affected children and their parents.
VanTuinen et al. (1988) found that the genes for myosin heavy chain-2 (160740), tumor antigen p53, and RNA polymerase II (180660), previously mapped to 17p, are not included in the MDS deletion region and therefore are unlikely to play a role in its pathogenesis.
Ledbetter
et
al. (1988) described 2 variable number tandem repeat (VNTR)
probes that
revealed a 15-kb region containing HTF islands that are likely to be
markers of
expressed sequences. Use of these probes showed homology to chromosome
11 in the
mouse. Because of the close location of MDCR to tumor antigen p53
(TP53; 191170)
and MYHSA1 (160730)
in man, the homologous locus in the mouse is probably close to the
corresponding
loci in that species. Several neurologic mutants in the mouse map to
that
region.
In 2 MDS
patients with normal chromosomes, a combination of somatic cell
hybrid, RFLP, and densitometric studies demonstrated deletion of
polymorphic
anonymous probes in the paternally derived chromosome 17 (VanTuinen
et al., 1988). This demonstration of submicroscopic deletion
suggests that
all MDS patients may have deletions at the molecular level. In an
addendum, the
authors stated that 3 additional MDS patients without cytogenetically
detectable
deletions had been found to have molecular deletions and that 'to date'
13 of 13
MDS patients had molecular deletions. Using anonymous probes, Schwartz
et al. (1988) likewise found molecular deletions in 3 MDS
patients, 2 of
whom had no visible abnormalities of chromosome 17. None of the 3 RFLP
loci
studied was absent in a case of lissencephaly without MDS.
Ledbetter
et
al. (1989) found that in all of 7 patients 3 overlapping
cosmids spanning
more than 100 kb were completely deleted, thus providing a minimum
estimate of
the size of the MDS critical region. A hypomethylated island and
evolutionarily
conserved sequences were identified within this 100-kb
region--indications of
the presence of one or more expressed sequences potentially involved in
the
pathophysiology of this disorder.
Reiner
et
al. (1993) cloned a gene called LIS1 (lissencephaly-1) in
17p13.3 that is
deleted in Miller-Dieker patients. Nonoverlapping deletions involving
either the
5-prime or the 3-prime end of the gene were found in 2 patients,
identifying
LIS1 as the disease gene. The deduced amino acid sequence showed
significant
homology to beta subunits of heterotrimeric G proteins, suggesting that
it may
be involved in a signal transduction pathway crucial for cerebral
development.
Since haploinsufficiency appears to lead to the syndrome, half the
normal dosage
of the gene product is apparently inadequate for normal development. It
may be
that improper proportions of beta and gamma subunits of a G protein
disturb
formation of the normal protein complex, as in hemoglobin H disease,
which is
caused by an imbalance in the ratio of alpha- to beta-globin. About 15%
of
patients with isolated lissencephaly and more than 90% of patients with
Miller-Dieker
syndrome have microdeletions in a critical 350-kb region of 17p13.3.
Genotype/phenotype studies are necessary to explain the phenotypic
differences. Neer
et al. (1993) commented on the nature of the newly found gene
and the
usefulness of identifying families of genes and the proteins they
encode.
Platelet-activating
factor (PAF) is involved in a variety of biologic and
pathologic processes (Hanahan,
1986). PAF acetylhydrolase, which inactivates PAF by removing
the acetyl
group at the sn-2 position, is widely distributed in plasma and tissue
cytosols.
One isoform of PAF acetylhydrolase present in bovine brain cortex is a
heterotrimer comprising subunits with relative molecular masses of 45,
30, and
29 kD (Hattori
et al., 1993). Hattori
et al. (1994) isolated the cDNA for the 45-kD subunit.
Sequence analysis
revealed 99% identity with the LIS1 gene, indicating that the LIS1 gene
product
is a human homolog of the 45-kD subunit of intracellular PAF
acetylhydrolase.
The results raised the possibility that PAF and PAF acetylhydrolase are
important in the formation of the brain cortex during differentiation
and
development.
Kohler
et
al. (1995) searched for microdeletions in 17p13.3 in 5
patients with
lissencephaly-1, typical features of Miller-Dieker syndrome and
apparently
normal karyotypes. Analysis of loci D17S5 and D17S379 by PCR and FISH
revealed a
deletion in 3 of the 5 cases. No deletion was observed in the other 2.
Given the
almost identical clinical picture of the 5 patients, the great
variation in the
molecular findings argued against Miller-Dieker syndrome being a
contiguous gene
syndrome.
Chong
et al.
(1996) characterized the LIS1 gene (601545),
demonstrating the presence of 11 exons. SSCP analysis of individual
exons was
performed on 18 patients with isolated lissencephaly sequence (ILS; see
607432)
who showed no deletions detectable by FISH. In 3 of these patients,
point
mutations were identified: a missense mutation, a nonsense mutation,
and a 22-bp
deletion at the exon 9-intron 9 junction predicted to result in a
splicing
error. The findings confirmed the view that mutations of LIS1 are the
cause of
the lissencephaly phenotype in ILS and in the Miller-Dieker syndrome.
Together
with the results of deletion analysis for other ILS and Miller-Dieker
syndrome
patients, these data are also consistent with the previous suggestion
that
additional genes distal to LIS1 are responsible for the facial
dysmorphism and
other anomalies in MDS patients.
Cardoso
et
al. (2003) completed a physical and transcriptional map of
the chromosome
17p13.3 region from LIS1 to the telomere. Using FISH, Cardoso
et al. (2003) mapped the deletion size in 19 children with
ILS (607432),
11 children with MDS, and 4 children with 17p13.3 deletions not
involving LIS1. Cardoso
et al. (2003) showed that the critical region that
differentiates ILS from
MDS at the molecular level can be reduced to 400 kb. Using somatic cell
hybrids
from selected patients, Cardoso
et al. (2003) identified 8 genes that are consistently
deleted in patients
classified as having MDS. These genes include ABR (600365),
14-3-3-epsilon (605066),
CRK (164762),
MYO1C (606538),
SKIP (603055),
PITPNA (600174),
SCARF1, RILP, PRP8 (607300),
and SERPINF1 (172860).
In addition, deletion of the genes CRK and 14-3-3-epsilon delineates
patients
with the most severe lissencephaly grade. On the basis of recent
functional data
and the creation of a mouse model suggesting a role for 14-3-3-epsilon
in
cortical development, Cardoso
et al. (2003) suggested that deletion of 1 or both of these
genes in
combination with deletion of LIS1 may contribute to the more severe
form of
lissencephaly seen only in patients with Miller-Dieker syndrome.
For rapid
diagnosis, Batanian
et al. (1990) used PCR in connection with probe YNZ22
(D17S5), a highly
polymorphic, variable number tandem repeat (VNTR) marker previously
shown to be
deleted in all patients with MDS, but not in patients with isolated
lissencephaly sequence. Analysis of 118 normal persons revealed 12
alleles
(differing in copy number of a 70-bp repeat unit) ranging in size from
168 to
938 bp.
Pollin
et
al. (1999) evaluated the risk of abnormal pregnancy outcome
in carriers of
balanced reciprocal translocations involving the MDS critical region in
17p13.3.
Fourteen families were ascertained on the basis of an affected index
case. In
these 14 families, 38 balanced translocation carriers had 127
pregnancies,
corrected for ascertainment bias by the exclusion of all index cases
and
carriers in the line of descent to the index cases. An abnormal
phenotype, an
unbalanced chromosome constitution, or both, were found in 33 of the
127 (26%)
pregnancies: 15 of 127 (12%) had MDS and an unbalanced karyotype with
del(17p);
9 of 127 (7%) had a less severe phenotype with dup(17p); and 9 were
unstudied,
although MDS with der(17) was usually suspected based on early death
and
multiple congenital anomalies. When unexplained pregnancy losses,
including
miscarriages and stillbirths, were excluded from the total, 33 of 99
(33%)
pregnancies were phenotypically or genotypically abnormal. The overall
risk of
abnormal pregnancy outcome of 26% was in the upper range of the
reported risk
for unbalanced offspring of carrier parents ascertained through
liveborn
aneuploid offspring. The risk increased to 33% when unexplained
pregnancy losses
were excluded from the total.
The condition
of so-called inverted pyramids is observed in the 'reeler'
mutation in mice (Landrieu
and Goffinet, 1981). The 'reeler' mutation (re) is located on
mouse
chromosome 5, a chromosome that carries no gene known thus far to be
homologous
to a gene on human chromosome 17. Thus, there is no support from
homology of
synteny for the notion that agyria in man is the same as 'reeler' in
the mouse.
The conserved sequences identified by Ledbetter et al. (1989) were mapped to mouse chromosome 11 by using mouse-rat somatic cell hybrids, thus extending the remarkable homology between human chromosome 17 and mouse chromosome 11 by 30 cM, into the 17p telomere region.
Yingling
et
al. (2003) discussed the prospects of using the mouse to
model Miller-Dieker
syndrome. Null and conditional knockout alleles in the mouse had been
generated
for Lis1 and Mnt (603039),
and null alleles had been produced for Hic1 (603825)
and 14-3-3-epsilon. For Lis1 and Pitpn (600174),
hypomorphic alleles also existed.
Victor A.
McKusick - updated : 10/13/2003
Victor A. McKusick - updated : 6/9/2003
Ada Hamosh - updated : 5/9/2003
Victor A. McKusick - updated : 8/31/1999
Michael J. Wright - updated : 2/12/1999
Iosif W. Lurie - updated : 8/6/1996
Victor A. McKusick : 6/3/1986
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=247200
.......................
Disorder Subdivisions
General Discussion
Classical lissencephaly, also known as lissencephaly type I, is a brain
malformation that may occur as an isolated abnormality (isolated
lissencephaly
sequence [ILS]) or in association with certain underlying syndromes
(e.g.,
Miller-Dieker syndrome, Norman-Roberts syndrome). The condition is
characterized
by absence (agyria) or incomplete development (pachygyria) of the
ridges or
convolutions (gyri) of the outer region of the brain (cerebral cortex),
causing
the brain's surface to appear unusually smooth.
In infants with classical lissencephaly, the head circumference may be
smaller
than would otherwise be expected (microcephaly). Additional
abnormalities may
include sudden episodes of uncontrolled electrical activity in the
brain
(seizures), severe or profound mental retardation, feeding
difficulties, growth
retardation, and impaired motor abilities. If an underlying syndrome is
present,
there may be additional symptoms and physical findings.
Researchers indicate that there may be various possible causes of
isolated
lissencephaly, including viral infections or insufficient blood flow to
the
brain during fetal development or certain genetic factors. 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 (known as XLIS or Doublecortin).
.
Organizations related to
Lissencephaly
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http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Lissencephaly
.......................
Miller-Dieker lissencephaly syndrome (MDLS)
| Syndrome | Miller-Dieker syndrome (MDS) |
|---|---|
| Synonyms | Miller-Dieker lissencephaly syndrome (MDLS) |
| agyria syndrome | |
| agyria-pachygyria syndrome | |
| classical lissencephaly | |
| hydrocephalic lissencephaly, is a major feature of |
| Summary | A developmental defect of the brain caused by incomplete neuronal migration and characterized by smoothness of the surface of the brain (lissencephaly) occurring in association with absence of the sulci and gyri (agyria) and thickening of the cerebral cortex with four rather than six layers (pachygyria), microcephaly, characteristic facial appearance, retarded growth and mental development, neurological complications, and multiple abnormalities of the brain, kidneys, heart, gastrointestinal tract, and other organs. Lissencephaly, once considered as synonymous with Walker-Warburg syndrome and Norman-Roberts syndrome, is now recognized as a component of several other syndromes. Type I (the classical form) is a component of Miller-Dieker and Norman-Roberts syndromes, also occurring as a separate entity; Type II the Walker-Warburg and muscle-eye-brain syndrome, also occurring in the Neu-Laxova syndrome. |
|---|---|
| Major Features | Head and neck: Microcephaly, prominent forehead, bitemporal hollowing, and micrognathia. |
| Ears: Malpositioned and/or malformed ears. | |
| Eyes: Abnormal irides, tortuous fundal vessels, telecanthus, hypertelorism, and mild blepharoptosis, | |
| Nose: Short nose with upturned nares and low nasal bridge. | |
| Mouth and oral structures: Long and thin the upper lip and late tooth eruption. | |
| Hand and foot: Clinodactyly, camptodactyly, and dermatoglyphic abnormal abnormalities consisting of irregular palmar creases. | |
| Muscles: Early hypotonia with subsequent hypertonia. | |
| Nervous system: Lissencephaly type I and agyria with or without regional thickening of the cerebral cortex (pachygyria); hypoplasia of the pontine nuclei and inferior olives; olivary heterotopia; and occasional small cerebellum, hypoplasia of the corpus callosum, dysplasia of the cerebral cortex structures, and midline calcification. Epilepsy and spastic paraplegia may be associated. | |
| Cardiovascular system: Cardiovascular defects vary and may include patent ductus arteriosus and ventricular septal defect. | |
| Urogenital system: Cryptorchidism, pilonidal sinus, kidney agenesis, and hydronephrosis are the most common anomalies. | |
| Temporal features: Death in infancy or childhood. | |
| Growth and development: Growth, mental, speech, and motor retardation. Polyhydramnios and decreased fetal movement may complicate prenatal development. | |
| Behavior and performance: Failure to thrive, decreased spontaneous activity, seizures, and feeding difficulty. | |
| Heredity: Transmitted as an autosomal recessive trait. Normal chromosomes are present in some cases but other are associated with chromosomal abnormalities which include deletion of the short arm of chromosome 17 (17p13.3, deletion of the short arm in association with duplication of the long arm of chromosome 17, ring chromosome l7, and 12q;17p translocation. |
http://www.nlm.nih.gov/mesh/jablonski/syndromes/syndrome456.html
===========================
References:
-------
The Lissencephaly Contact Group (1)
Cephalic Disorders Fact Sheet - NIH (3)
===========================
Abstracts and Clinical Studies
-------
Molecular genetics of lissencephaly and microcephaly - April 2008
Molecular mechanism of lissencephaly--how LIS1 and NDEL1 regulate cytoplasmic dynein - April 2008
Genetic mechanisms underlying abnormal neuronal migration in classical lissencephaly - Dec 2007
Lissencephaly and LIS1: insights into the molecular mechanisms of neuronal migration and development - Oct 2007
Molecular heterogeneity in fetal forms of type II lissencephaly -Oct 2007
Genetic and clinical aspects of lissencephaly - May 2007
Partial deletion of LIS1: a pitfall in molecular diagnosis of Miller-Dieker syndrome - April 2007
===========================
External Links Information:
-------
The Lissencephaly Launch Pad
http://homepage.ntlworld.com/foliot/liss/
.......................
The Lissencephaly Book Shop
http://homepage.ntlworld.com/foliot/liss/lissbooks.htm
.......................
Classical Lissencephaly Syndromes
http://www.lissencephaly.org/medical/info/classlis.htm
.......................
NINDS Lissencephaly Information Page
http://www.ninds.nih.gov/disorders/lissencephaly/lissencephaly.htm
===========================
Support Groups:
-------
Lissencephaly Network - Support
.......................
England
- United Kingdom
The Lissencephaly Contact
Group
http://www.lissencephaly.org.uk
info@lissencephaly.org.uk
Mrs. Nayyer Ahmed: Telephone: 01562
851429 (outside the UK +
44 1562 851429)
.......................
Austrailia
Lissencephaly Network
Australia
Contact: Mrs Debbie Tuivawa
76 Whitaker Street
Guildford 2161 NSW Australia
(02) 9632 5914
.......................
Germany
LISS e. V.
(Deutsch)
http://www.lissenzephalie.de/
Contact: Burkhard Propf
Corduaweg 16
21075 Hamburg
Germany
propf.burkhard@t-online.de
+49407927432
.......................
Online Support Group
Lissencephaly
http://health.groups.yahoo.com/group/lissencephaly/
.......................
Online Support Group
Miller-Dieker Lissencephaly
http://health.groups.yahoo.com/group/millerdieker/
===========================
Codes and External Resources:
ICD-10
| Q04.3 | Other reduction deformities of brain | |||||||
| Absence Agenesis Aplasia Hypoplasia |
} } } } |
of part of brain |
||||||
| Agyria Hydranencephaly Lissencephaly Microgyria Pachygyria |
||||||||
| Excludes: | congenital malformations of
corpus callosum |
|||||||
ICD-9
OMIM
===========================
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