This paper reports the brain magnetic resonance imaging (MRI) findings of a case of merosin-deficient congenital muscular dystrophy (MDCMD) in a neonate and discusses the spectrum of brain involvement in MDCMD. A neonate presented hypotonia, increased serum creatine kinase levels, and polymicrogyria and subcortical heterotopia on brain MRI involving both posterior temporal and occipital lobes. Although these findings suggested Fukuyama muscular dystrophy, muscle biopsy showed dystrophic changes and an absence of merosin staining. We found that compound heterozygous mutation for c.2049_2050delAG (p.R683fs) and c.5866-2A>G in the LAMA2 gene which encodes Laminin-α2. To our knowledge, this is the second Korean case of MDCMD with polymicrogyria and subcortical heterotopias. This case shows that a range of brain structural malformations can be found in children with MDCMD and that the classification of congenital muscular dystrophy (CMD) is not complete yet, as indicated previously in reports suggesting other unclassified forms of CMD.
Biopsy ; Brain ; Child ; Classical Lissencephalies and Subcortical Band Heterotopias ; Classification ; Creatine Kinase ; Humans ; Infant, Newborn ; Laminin ; Magnetic Resonance Imaging ; Muscle Hypotonia ; Muscular Dystrophies* ; Occipital Lobe ; Polymicrogyria* ; Walker-Warburg Syndrome

Miller-Dieker syndrome is a contiguous gene deletion syndrome involving chromosome 17p13.3, which is characterized by type 1(classical) lissencephaly and typical craniofacial abnormalities. Children with Miller-Dieker syndrome have profound psychomotor retardation, seizures that often are intractable, chronic feeding problems that lead to recurrent pneumonia, and shortened lifespan. We have experienced a Miller-Dieker syndrome female who has lived to 8years, showing severe mental and motor retardation and intractable epilepsy. She was diagnosed as Miller-Dieker syndrome in the neonatal period, showing typical facial features, type 1 lissencephaly, and chromosome 17p13.3 microdeletion in fluorescence in situ hybridization. Infantile spasm occurred at 4 months of age and progressed to Lennox-Gastaut syndrome at 3 years and 6 months, both of which were not controlled by antiepileptic drugs.
Child ; Classical Lissencephalies and Subcortical Band Heterotopias ; Craniofacial Abnormalities ; Epilepsy ; Female ; Fluorescence ; Gene Deletion ; Humans ; In Situ Hybridization ; Infant ; Infant, Newborn ; Intellectual Disability ; Lissencephaly ; Pneumonia ; Seizures ; Spasms, Infantile

Miller-Dieker Syndrome consists of severe type I lissencephaly and a characteristic abnormal facial appearance at birth and may progress to severe neurologic defects such as intractable seizure and growth failure. This syndrome is associated with microdeletion of p13.3 in the distal portion of chromosome 17. Lissencephaly is a brain malformation manifested by a smooth cerebral surface, thickened cortical mantle, and microscopic evidence of incomplete neuronal migration. We diagnosed Miller-Dieker syndrome in a case in which there are charcteristic craniofacial appearance and neurologic symptoms and type I lissencephaly on the MRI. : We confirmed this syndrome with the a microdeletion of p13.3 portion in the short arm of chromosome 17 by the FISH method. We have experienced a baby with this syndrome, who showed characterisic craniofacial abnormalities and a microdeletion of p13.3 portion in the short arm of chromosome 17. Then we report this rare case with brief review of literature.
Arm ; Brain ; Chromosomes, Human, Pair 17 ; Classical Lissencephalies and Subcortical Band Heterotopias* ; Craniofacial Abnormalities ; Lissencephaly ; Magnetic Resonance Imaging ; Neurologic Manifestations ; Neurons ; Parturition ; Seizures

Lissencephaly is a rare disorder that is characterized by the disorganized and unlayered cortex. The cause of this disorder is related to chromosomal abnormalities or infection. The pathogenesis of lissencephaly is faulty migration of neuroblast. Lissencephaly is associated with Dandy-Walker syndrome and Miller-Dieker syndrome. A woman at 35 weeks of gestaion was transferred to our hospital due to abnormal antenatal sonographic findings (ventricular dilation and decreased sulci in cerebral cortex after 31 weeks of gestation). The antenatal studies showed none-specific findings. The infant was diagnosed lissencephaly by postnatal MRI evaluation and showed normal karyotype. We report the prenatal diagnosis of lissencephaly case with a literature.
Cerebral Cortex ; Chromosome Aberrations ; Classical Lissencephalies and Subcortical Band Heterotopias ; Dandy-Walker Syndrome ; Female ; Humans ; Infant ; Karyotype ; Lissencephaly* ; Magnetic Resonance Imaging* ; Prenatal Diagnosis ; Ultrasonography

Lissencephaly results from a neuromigrational arrest during first and second trimester of pregnancy and shows hypotonia, marked mental retardation and seizure as predominant features. Myelination is a perinatal process and co-occurence of migrational disorder with myelination disorder is rare. We report a 17-month-old male with mixed quadriplegia and mental retardation with type 1 lissencephaly and dysmyelination of cerebral white matter diagnosed by magnetic resonance imaging.
Classical Lissencephalies and Subcortical Band Heterotopias ; Female ; Humans ; Infant ; Intellectual Disability ; Lissencephaly* ; Magnetic Resonance Imaging ; Male ; Muscle Hypotonia ; Myelin Sheath ; Pregnancy ; Pregnancy Trimester, Second ; Quadriplegia* ; Seizures

No abstract available.
Lissencephaly* ; Walker-Warburg Syndrome

Miller-Dieker Syndrome (MDS) is a contiguous gene deletion syndrome of chromosome 17p13.3, characterized by classical lissencephaly (lissencephaly type 1) and distinct facial features. Children with MDS present with severe developmental delay, epilepsy and feeding problems. The lissencephaly represents the severe end of the spectrum with generalized agyria, or agyria and some frontal pachy- gyria. Prenatal diagnosis is available and consists of fetal chromosomal analysis by karyotyping or fluorescence in situ hybridization (FISH), on chorion villus sampling or amniocentesis. Sonographic diagnosis in general cannot be accomplished earlier than late second trimester, when the characteristic cerebral anomalies can be noted. The progressive microcephaly and failure of development of both sulci and gyri are suggestive of lissencephaly. We report the case of a pregnant woman of 24 weeks gestation who presented with ventriculomegaly on antenatal sonography and hydrocephalus, and corpus callosum agenesis on fetal MRI, which was diagnosed as MDS by karyotyping and FISH on amniocentesis.
Agenesis of Corpus Callosum ; Amniocentesis ; Child ; Chorion ; Classical Lissencephalies and Subcortical Band Heterotopias* ; Diagnosis ; Epilepsy ; Female ; Fluorescence ; Gene Deletion ; Humans ; Hydrocephalus ; In Situ Hybridization ; Karyotyping ; Lissencephaly ; Magnetic Resonance Imaging ; Microcephaly ; Pregnancy ; Pregnancy Trimester, Second ; Pregnant Women ; Prenatal Diagnosis ; Ultrasonography

A 9-year-old Korean boy with lissencephaly was found dead at home. He had previously been diagnosed with lissencephaly that presented with infantile spasm on the basis of magnetic resonance imaging and electroencephalogram results. Antemortem chromosomal banding revealed a normal karyotype. A legal autopsy was requested to eliminate the possibility of neglect or abuse by his parents. The autopsy findings revealed type I lissencephaly with the associated microcephaly. No external wounds or decubitus ulcers were noted. Postmortem fluorescence in situ hybridization for the LIS1 locus and nucleotide sequence analysis of the whole coding regions of the LIS1 gene did not reveal any deletions. The antemortem and postmortem findings revealed that lissencephaly syndrome was associated with isolated lissencephaly sequence. External causes of death were excluded by the full autopsy and toxicology test results. Because patients with mental retardation are frequently victimized and suffer neglect or abuse, thorough external and internal examinations should be conducted at the time of autopsy.
Autopsy ; Base Sequence ; Cause of Death ; Child ; Child Abuse ; Classical Lissencephalies and Subcortical Band Heterotopias ; Clinical Coding ; Electroencephalography ; Fluorescence ; Forensic Pathology ; Humans ; In Situ Hybridization ; Infant ; Infant, Newborn ; Intellectual Disability ; Karyotype ; Lissencephaly ; Magnetic Resonance Imaging ; Microcephaly ; Parents ; Pressure Ulcer ; Spasms, Infantile ; Toxicology

Miller-Dieker syndrome is a multiple malformation syndrome characterized by severe lissencephaly and characteristic facial abnormalities at birth. It is associated with visible or submicroscopic deletions within chromosome 17p13.3 including PAFAH1B1 (LIS1) gene. We report a six-month-old boy who presented with spasm and generalized myoclonic seizures. The patient was born at 40 weeks' gestation to a 36-year-old woman and showed developmental delay without microcephaly or prominent facial abnormality. Magnetic resonance imaging of the brain showed a few gyrus (lissencephaly). High resolution cytogenetic analysis from peripheral blood showed a normal karyotype. However, fluorescence in situ hybridization (FISH) of the metaphase chromosome using Miller-Dieker/ILS probe (Oncor, Gaithersburg, Maryland, USA) revealed only one signal of probe, indicating a microdeletion of 17pl3.3 region including PAFAH1B1 (LIS1) gene. We suggest that FISH 17p13.3 studies should be performed in addition to a standard metaphase analysis in patients with lissencephaly even if facial anomaly is not noted. A confirmatory diagnosis using FISH would be helpful in terms of leading to allow genetic counseling and availability prenatal diagnosis to the family.
Adult ; Brain ; Classical Lissencephalies and Subcortical Band Heterotopias* ; Cytogenetic Analysis ; Diagnosis ; Female ; Fluorescence ; Genetic Counseling ; Humans ; In Situ Hybridization ; Karyotype ; Lissencephaly ; Magnetic Resonance Imaging ; Male ; Maryland ; Metaphase ; Microcephaly ; Parturition ; Pregnancy ; Prenatal Diagnosis ; Seizures ; Spasm

Adolescent ; Classical Lissencephalies and Subcortical Band Heterotopias ; diagnosis ; Female ; Humans