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

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 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

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

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

OBJECTIVETo detect potential mutation of Doublecortin (DCX) gene in a patient featuring X-linked subcortical laminar heterotopia (X-SCLH) and epilepsy.

METHODSMutation of the DCX gene was screened by PCR and direct sequencing. Pathogenicity of the mutation was analyzed with a PolyPhen-2 software.

RESULTSA de novo missense mutation c.971T>C (p.Phe324Ser) was discovered.

CONCLUSIONA diagnostic method for X-SCLH has been established, which may facilitate diagnosis and genetic counseling of patients featuring this disease.

Agenesis of Corpus Callosum ; diagnosis ; genetics ; Base Sequence ; Brain ; pathology ; Child ; Classical Lissencephalies and Subcortical Band Heterotopias ; diagnosis ; genetics ; Electroencephalography ; Epilepsy ; diagnosis ; genetics ; Exons ; Female ; Humans ; Magnetic Resonance Imaging ; Microtubule-Associated Proteins ; genetics ; Mutation ; Neuropeptides ; genetics

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

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

OBJECTIVETo report on prenatal diagnosis of a fetus with Miller-Dieker syndrome (MDS) and explore its genotype - phenotype correlation.

METHODSChromosome karyotyping, bacterial artificial chromosome on beads (BACs-on-Beads, BoBs), fluorescence in situ hybridization (FISH), and single nucleotide polymorphism microarray (SNP array) were applied in conjunction for the prenatal diagnosis of a fetus with abnormal ultrasound findings.

RESULTSA 17p13.3 microdeletion was detected with the BoBs assay, and the result was confirmed by FISH. With the SNP array, the deletion was mapped to chromosome 17, with its range determined to be 5.2 Mb. On high-resolution banding analysis and BoB assay, the deletion was not found in either parent.

CONCLUSIONThe combined use of BoBs, FISH and SNP array has enabled prenatal diagnosis of a fetus with MDS. Attention should be paid to microdeletions and microduplications which can be missed by conventional chromosomal karyotyping analysis.

Adult ; Chromosome Deletion ; Chromosomes, Human, Pair 17 ; Classical Lissencephalies and Subcortical Band Heterotopias ; diagnosis ; genetics ; Female ; Genetic Association Studies ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Polymorphism, Single Nucleotide ; Pregnancy ; Prenatal Diagnosis

BACKGROUND: Microdeletion syndromes not detectable by conventional cytogenetic analysis have been reported to occur in approximately 5% of patients with unexplained mental retardation (MR). Therefore, it is essential to ensure that patients with MR are screened for these microdeletion syndromes. Mental retardation syndrome multiplex ligation-dependent probe amplification (MRS-MLPA) is a new technique for measuring sequence dosages that allows for the detection of copy number changes of several microdeletion syndromes (1p36 deletion syndrome, Williams syndrome, Smith-Magenis syndrome, Miller-Dieker syndrome, DiGeorge syndrome, Prader-Willi/Angelman syndrome, Alagille syndrome, Saethre-Chotzen syndrome, and Sotos syndrome) to be processed simultaneously, thus significantly reducing the amount of laboratory work. METHODS: We assessed the performance of MLPA (MRC-Holland, The Netherlands) for the detection of microdeletion syndromes by comparing the results with those generated using FISH assays. MLPA analysis was carried out on 12 patients with microdeletion confirmed by FISH (three DiGeorge syndrome, four Williams syndrome, four Prader-Willi syndrome, and one Miller-Dieker syndrome). RESULTS: The results of MLPA analysis showed a complete concordance with FISH in 12 patients with microdeletion syndromes. CONCLUSIONS: On the basis of these results, we conclude that MLPA is an accurate, reliable, and cost-effective alternative to FISH in the screening for microdeletion syndromes.
*Chromosome Deletion ; Classical Lissencephalies and Subcortical Band Heterotopias/genetics ; DiGeorge Syndrome/genetics ; Humans ; In Situ Hybridization, Fluorescence/*methods ; Laboratories, Hospital ; Mental Retardation/*diagnosis/genetics ; Nucleic Acid Amplification Techniques/*methods ; Prader-Willi Syndrome/genetics ; Williams Syndrome/genetics