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

OBJECTIVE: To explore the clinical characteristics and genetic basis for a child with X-linked lissencephaly with abnormal genitalia (XLAG). METHODS: A child with XLAG who had presented at the Third Affiliated Hospital of Zhengzhou University in May 2021 was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to high-throughput sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the result was analyzed by using bioinformatic software. RESULTS: The child was found to have harbored a hemizygous c.945_948del variant in exon 2 of the ARX gene, which as a frameshifting variant has resulted in a truncated protein. His mother was found to be heterozygous for the variant, whilst his father was of wild type. The variant was unreported previously. CONCLUSION The hemizygous c.945_948del variant of the ARX gene probably underlay the XLAG in this patient. Above finding has provided a basis for the diagnosis and genetic counseling for this family.
Humans ; Child ; Classical Lissencephalies and Subcortical Band Heterotopias ; Exons ; Computational Biology ; Genetic Counseling ; Genitalia ; Transcription Factors ; Homeodomain Proteins

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

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

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

OBJECTIVETo investigate the prenatal ultrasonic manifestations of fetal gray matter heterotopias (FGMH) and evaluate the optimal method its prenatal diagnosis.

METHODSThe prenatal and postnatal ultrasound images and MRI images were analyzed for a fetus with a definitive diagnosis of FGMH. The detection rates of FGMH by prenatal ultrasound and MRI reported in literature were compared.

RESULTSWe identified 11 reports of FGMH from 1998 to 2015, involving 43 cases with prenatal diagnoses. Of the total of 44 cases (including our case), 32 that had been confirmed postpartum had prenatal ultrasound and MRI data, which showed a significantly lower detection rates of FGMH by prenatal ultrasound than by MRI (43.8% vs 93.8%, P<0.001).

CONCLUSIONPrenatal ultrasound can only detect subependymal heterotopia with characteristic manifestations, and the detection of other types of FGMH relies on MRI, which is currently the best option for prenatal diagnosis of FGMH.

Classical Lissencephalies and Subcortical Band Heterotopias ; diagnosis ; Female ; Fetal Diseases ; diagnosis ; Fetus ; Gray Matter ; pathology ; Humans ; Magnetic Resonance Imaging ; Pregnancy ; Prenatal Diagnosis ; Ultrasonography, Prenatal

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

OBJECTIVE: To carry out genetic diagnosis for a fetus. METHODS: Chromosome G-banding and chromosomal microarray analysis (CMA) were carried out for a fetus with abnormal morphology of lateral cerebral fissure. RESULTS: The karyotype of the fetus was normal, but CMA showed that it has carried a 1.4 Mb deletion at 17p13.3 region, which suggested a diagnosis of Miller-Dieker syndrome (MDS). CONCLUSION Familiarity with clinical features and proper selection of genetic testing method are crucial for the diagnosis of MDS. Attention should be paid to microdeletions and microduplications which can be missed by conventional chromosomal karyotyping.
Chromosome Banding ; Chromosome Deletion ; Chromosomes, Human, Pair 17 ; Classical Lissencephalies and Subcortical Band Heterotopias/genetics* ; Female ; Fetus ; Humans ; Karyotyping ; Pregnancy ; Prenatal Diagnosis

OBJECTIVE: To explore the genetic basis for fetus with bilateral lateral ventriculomegaly. METHODS: Fetus umbilical cord blood and peripheral blood samples of its parents were collected. The fetus was subjected to chromosomal karyotyping, whilst the fetus and its parents were subjected to array comparative genomic hybridization (aCGH). The candidate copy number variation (CNV) were verified by qPCR, Application goldeneye DNA identification system was used to confirm the parental relationship. RESULTS: The fetus was found to have a normal karyotype. aCGH analysis indicated that it has carried a 1.16 Mb deletion at 17p13.3, which partially overlapped with the critical region of Miller-Dieker syndrome (MDS), in addition with a 1.33 Mb deletion at 17p12 region, which is associated with hereditary stress-susceptible peripheral neuropathy (HNPP). Its mother was also found to harbor the 1.33 Mb deletion at 17p12. qPCR analysis confirmed that the expression levels of genes from the 17p13.3 and 17p12 regions were about the half of that in the normal control, as well as the maternal peripheral blood sample. Parental relationship was confirmed between the fetus and its parents. Following genetic counseling, the parents has chosen to continue with the pregnancy. CONCLUSION The fetus was diagnosed with Miller-Dieker syndrome due to the de novo deletion at 17p13.3. Ventriculomegaly may be an important indicator for prenatal ultrasonography in fetuses with MDS.
Pregnancy ; Female ; Humans ; Classical Lissencephalies and Subcortical Band Heterotopias ; Comparative Genomic Hybridization ; DNA Copy Number Variations ; Fetus ; Hydrocephalus ; Prenatal Diagnosis ; Chromosome Deletion