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Biomedical subjects

D Lev

Publications and source records attributed to D Lev.

At least 19 recordsLinked to original sources
PubMed2007

Prenatal diagnosis of malformations of cortical development by dedicated neurosonography.

OBJECTIVE: Malformations of cortical development (MCD) are rarely diagnosed in utero. We describe and compare the ultrasonographic and pathology findings in a cohort of fetuses with MCD. METHODS: Fetuses with MCD were identified among all fetuses evaluated for suspected brain anomalies at the Fetal Neurology Clinic, and the ultrasonographic findings were compared with the results of the pathology examination. RESULTS: We suspected the presence of MCD by ultrasonography in 23 fetuses. The mean gestational age at the time of ultrasound diagnosis was 26.2 (range, 18-40) weeks. The ultrasonographic findings leading to the diagnosis of MCD were abnormally overdeveloped gyri and sulci for gestational age (n = 7), delay in sulcation (n = 5), abnormally thin cortex (n = 5) abnormally wide and broad sulci (n = 3), bulging into the lateral ventricle (n = 1), cortical cleft (n = 1), and multiple intraparenchymal echogenic nodules (n = 1). All fetuses had associated central nervous system (CNS) and/or non-CNS anomalies. Pathology examination (performed in 17 fetuses) confirmed MCD in 16. CONCLUSIONS: Cortical malformations can be diagnosed in utero by ultrasonography based on the presence of specific deviations from the normal pattern of development. The identified cases may represent the more severe forms in the MCD spectrum. The pathology findings do not always conform to the current classification systems of MCD but help in differentiating between possible genetic and acquired etiologies and in some cases provide a definitive syndromic diagnosis.

Cerebral Cortex↗
PubMed2006

Normal and abnormal fetal brain development during the third trimester as demonstrated by neurosonography.

The multiplanar neurosonographic examination of the fetus enables superb visualization of brain anatomy during pregnancy. The examination may be performed using a transvaginal or a transfundal approach and it is indicated in patients at high risk for CNS anomalies or in those with a suspicious finding during a routine examination. The purpose of this paper is to present a description of the normal brain and of abnormal findings usually diagnosed late in pregnancy, including malformations of cortical development, infratentorial anomalies, and prenatal insults.

Brain↗
PubMed2006

Sonographic developmental milestones of the fetal cerebral cortex: a longitudinal study.

OBJECTIVE: To identify sonographic landmarks of normal fetal cortical development. METHODS: Serial ultrasound examinations were performed every 2 weeks from 18 weeks of gestation until term. In each session a detailed examination of the fetal brain was performed and the appearance of the main sulci and gyri was recorded. RESULTS: Twenty-two pregnant women volunteered to participate in the study. The fetal cortex followed an orderly pattern of development. By the time of the first ultrasound examination, at 18 weeks, the major fissures were present. The first sulci could be demonstrated as early as 18 weeks. Main landmarks, represented by the parieto-occipital fissure and the cingulate and calcarine sulci, were present between 22-24 weeks. The central sulcus was present in all cases by 28 weeks. By 30-32 weeks most of the main sulci could be demonstrated. CONCLUSIONS: Prenatal sonographic examinations can accurately demonstrate structures of the fetal cortex. Comparison of our results with those of both magnetic resonance imaging and other sonographic studies shows similarities in the order of appearance of the sulci and gyri, with only minor differences in the exact gestational age at which they are detected. Accurate knowledge of the ultrasound appearance of the fetal cortex at different stages of gestation is important in order to be able to diagnose in-utero malformations of cortical development.

Cerebral Cortex↗
PubMed2005

Fulminant neurological deterioration in a neonate with Leigh syndrome due to a maternally transmitted missense mutation in the mitochondrial ND3 gene.

Leigh syndrome can result from both nuclear and mitochondrial DNA defects. Mutations in complex V genes of the respiratory chain were considered until recently as the most frequent cause for mitochondrial inherited Leigh syndrome, while gene defects in complex I were related to recessive Leigh syndrome. Recently few reports of mutations in the mitochondrial-encoded complex I subunit genes causing Leigh syndrome have been reported. We describe a 1-month-old baby who acutely deteriorated, with abrupt onset of brainstem dysfunction, due to basal ganglia lesions extending to the brainstem. A muscle biopsy demonstrated complex I deficiency. Subsequent analysis of the mitochondrial genome revealed a homoplastic T10191C mutation in the ND3 gene (in blood and muscle), resulting in a substitution of serine to proline. Hair root analysis revealed a 50% mutant load, reflecting heteroplasmy in early embryonic stages. The mutation was also detected in his mother (5%). Western blot analysis revealed a decrease of the 20 kDa subunit (likely ND6) and of the 30 kDa subunit (NDUFA9), which is probably due to instability attributed to the inability to form subcomplexes with ND3. This is the first description of infantile Leigh syndrome due to a maternally transmitted T10191C substitution in ND3 and not due to a de novo mutation. This mutation is age and tissue dependent and therefore may not be amenable to prenatal testing.

DNA, Mitochondrial↗
PubMed2005

Differential diagnosis in fetuses with absent septum pellucidum.

OBJECTIVE: To elucidate the characteristic morphological features that may help in the prenatal differential diagnosis of absent septum pellucidum as demonstrated by ultrasound. METHODS: Twenty-six fetuses were referred to the fetal neurology clinic due to mild to severe ventriculomegaly and a connection between the lateral ventricles. The following ultrasonographic features were evaluated: place and extent of the ventricular communication, non-cleavage of the hemispheres and deep gray nuclei, callosal anomalies, position of the choroid plexus, and other central nervous system and facial or body anomalies. A flowchart was created in order to facilitate the final diagnosis. RESULTS: The presence of non-cleavage and/or characteristic facial anomalies prompted the diagnosis of holoprosencephaly (HPE) in 14 fetuses, including two fetuses with the middle interhemispheric variant. Ten fetuses were diagnosed as having hydrocephalus based on the lack of the same features and the observation that the communication between the lateral ventricles was at the level of the third ventricle with almost normal anterior and posterior segments. In two fetuses the diagnosis of septo-optic dysplasia vs. isolated agenesis of the cavum septi pellucidi was contemplated. CONCLUSIONS: The use of the proposed flowchart enabled differentiation between hydrocephalus and HPE. The communication between the ventricles in hydrocephalic fetuses may be due to a disruption of the septum pellucidum or to a pathological enlargement of the foramen of Monro. Published by John Wiley & Sons, Ltd.

Diagnosis, Differential↗
PubMed2005

A novel missense mutation in the Connexin 26 gene associated with autosomal recessive sensorineural deafness.

Mutations in the Connexin 26 (Cx26) gene (GJB2) are a common cause of hereditary hearing impairment. We report the identification of a novel point mutation in the Cx26 gene, Leu205Pro(L205P), linked to familial, autosomal recessive sensorineural hearing loss. This missense mutation, causing amino acid leucine at position 205 to be substituted by proline, is located in the highly conserved sequence of the fourth transmembrane domain (TM4) of Cx26. Hearing loss with this mutation occurred in a Georgian Jewish family, was congenital, moderate to profound and nonprogressive. We have shown that the new mutation L205P in Cx26 is strongly associated with congenital NSHL. Multiple-sample screening for this mutation can be easily performed with a mismatch PCR that creates a restriction site.

Alleles↗
PubMed2004

Clinical presentations of mitochondrial cardiomyopathies.

UNLABELLED: To determine the clinical manifestations and interfamilial variability of patients diagnosed with a mitochondrial cardiomyopathy, we reviewed the charts of 14 patients with cardiomyopathy out of 59 patients with mitochondrial disorders who attended the mitochondrial disease clinic at Wolfson Medical Center from 1996 to 2001. All patients underwent a metabolic evaluation including blood lactate, pyruvate, carnitine, and amino acids and urine organic acids. Respiratory chain enzymes were assessed in 10 patients. The mitochondrial DNA (mtDNA) was assessed for mutations. The age at presentation ranged between 6 months and 24 years. Six of the patients died, 5 from heart failure. The cardiomyopathy was hypertrophic in 10 and dilated in 4. Conduction and rhythm abnormalities were present in 6. Eleven patients had family members with mitochondrial disorders. All the patients had additional involvement of one or more systems. Seven patients exhibited a deficiency of a respiratory chain enzyme in the muscle. The MELAS mtDNA point mutation (3243) was found in one patient. Blood lactic acid levels were increased in 5. Brain MRI abnormalities were observed in 4. CONCLUSIONS: Mitochondrial dysfunction frequently affects the heart and may cause both hypertrophic and dilated cardiomyopathy. The cardiomyopathy is usually a part of a multisystem involvement and may rarely be isolated. The course may be stable for many years, but rapid deterioration may occur. Understanding the biochemical and genetic features of these diseases will enable us to comprehend the clinical heterogeneity of these disorders.

Adolescent↗
PubMed2004

Fetal brain imaging: a comparison between magnetic resonance imaging and dedicated neurosonography.

OBJECTIVES: To evaluate whether fetal brain magnetic resonance imaging (MRI) adds useful clinical information to that obtained by dedicated fetal neurosonography using a combined transabdominal and transvaginal approach in fetuses with suspected brain anomalies. METHODS: In the 2-year period between January 2000 and January 2002, 42 fetuses underwent neurosonographic and MRI examinations of the brain. The referral indications were: asymmetric ventriculomegaly (13), ventriculomegaly (7), periventricular cysts (2), suspected midline findings (7), agenesis of the corpus callosum (3), infratentorial pathology (3), cytomegalovirus (CMV) infection (2) and miscellaneous indications (5). RESULTS: Neurosonography and MRI produced similar diagnoses in 29 fetuses: normal examination (10), isolated asymmetric ventriculomegaly (11), isolated ventriculomegaly (3), periventricular cysts (2), agenesis of the corpus callosum (1), pericallosal lipoma (1) and cerebellar hemorrhage (1). The neurosonographic diagnoses were more accurate in seven patients: hemimegalencephaly, pericallosal lipoma, signs of CMV infection, brain anomalies associated with agenesis of the corpus callosum and three fetuses with a normal ultrasound scan in which MRI suggested a parenchymal abnormality. MRI provided a more accurate diagnosis in three patients: a third ventricular dilatation was ruled out, normal ventricles in a fetus with an ultrasonographic finding of asymmetric ventricles, and diagnosis of progression of asymmetric ventriculomegaly. In three patients the identified pathologies were differently interpreted, each examination provided another aspect of the anomaly or a definitive diagnosis was not possible. CONCLUSIONS: Our study demonstrated that dedicated neurosonography is equal to MRI in the diagnosis of fetal brain anomalies. In most of the cases MRI confirmed the ultrasonographic diagnosis; in a minority of cases each modality provided additional/different information. The major role of MRI was in reassurance of the parents regarding the presence or absence of brain anomalies.

Agenesis of Corpus Callosum↗
PubMed2003

Neonatal liver failure and Leigh syndrome possibly due to CoQ-responsive OXPHOS deficiency.

CoQ transfers electrons from complexes I and II of the mitochondrial respiratory chain to complex III. There are very few reports on human CoQ deficiency. The clinical presentation is usually characterized by: epilepsy, muscle weakness, ataxia, cerebellar atrophy, migraine, myogloblinuria and developmental delay. We describe a patient who presented with neonatal liver and pancreatic insufficiency, tyrosinemia and hyperammonemia and later developed sensorineural hearing loss and Leigh syndrome. Liver biopsy revealed markedly reduced complex I+III and II+III. Addition of CoQ to the liver homogenate restored the activities, suggesting CoQ depletion. Histological staining showed prominent bridging; septal fibrosis and widening of portal spaces with prominent mixed inflammatory infiltrate, associated with interface hepatitis, bile duct proliferation with numerous bile plugs. Electron microscopy revealed a large number of mitochondria, which were altered in shape and size, widened and disordered intercristal spaces. This may be the first case of Leigh syndrome with liver and pancreas insufficiency, possibly caused by CoQ responsive oxphos deficiency.

Biopsy↗
PubMed2003

The first nonsense mutation in alsin results in a homogeneous phenotype of infantile-onset ascending spastic paralysis with bulbar involvement in two siblings.

Eight mutations in the ALS2 gene have been described as causing autosomal-recessive juvenile-onset forms of the motor neuron diseases amyotrophic lateral sclerosis, primary lateral sclerosis and hereditary spastic paraplegia. All mutations are small deletions that are predicted to result in a frameshift and premature truncation of the alsin protein. Here we describe a ninth ALS2 mutation, in two siblings affected by infantile-onset ascending spastic paraplegia with bulbar involvement. This mutation is predicted to result in the substitution of an amino acid by a stop codon, and thus is the first nonsense mutation detected in this gene. It is probable that full-length alsin is required for the proper development and/or functioning of upper motor neurons.

Age of Onset↗
PubMed2002

Reversible fulminant lactic acidosis and liver failure in an infant with hepatic cytochrome-c oxidase deficiency.

Cytochrome-c oxidase (COX) is the most common respiratory chain complex involved in liver failure, either as a single enzyme deficiency or as part of multiple enzyme deficiencies. We describe an infant who presented with fulminant lactic acidosis in the neonatal period. The lactic acidosis resolved spontaneously but liver and pancreatic insufficiency ensued. Isolated cytochrome-c oxidase deficiency was found in liver but not in muscle and fibroblasts. mtDNA rearrangements or depletion were ruled out. By the age of one year, liver and pancreatic functions have normalized completely and neurodevelopment is normal.

Acidosis, Lactic↗
PubMed2002

Germline mutations in the PTEN gene in Israeli patients with Bannayan-Riley-Ruvalcaba syndrome and women with familial breast cancer.

Germline mutations in BRCA1 or BRCA2 account for the majority of inherited breast cancer cases. Yet, in up to 40% of familial breast cancer cases, no mutations can be detected in either gene. Germline mutations in PTEN underlie two inherited syndromes: Cowden disease (CD) and Bannayan-Riley-Ruvalcaba syndrome (BRRS). The known association of CD with breast cancer risk made it plausible that germline mutations within PTEN may play a role in inherited predisposition to breast cancer. The nine coding exons of the PTEN gene were screened for harboring germline mutations using denaturing gradient gel electrophoresis (DGGE) complemented by sequencing, in two subsets of Israeli patients: 12 patients clinically diagnosed with BRRS, and 89 women with an apparent inherited predisposition to breast cancer, some with salient features of CD. Two of three familial BRRS patients exhibited novel germline mutations in PTEN: a missense mutation changing methionine to arginine at codon 134, and insertion of two nucleotides (CA) at cDNA position 1215 resulting in a frameshift at codon 61 and a premature stop at codon 99. Among 89 high-risk women, two missense mutations were detected in exon 4: A to C change at cDNA position 1279 resulting in a change of aspargine to threonine at codon 82 (N82T), and a G to an A alteration in 1269 which alters threonine to alanine at codon 78 (T78A), a non-conservative missense mutation. This study suggests that PTEN does not play a major role in predisposing to hereditary breast cancer in Israeli women, and that detection of PTEN mutations in BRRS patients is more likely in familial cases.

Breast Neoplasms↗
PubMed2002

A normal second-trimester ultrasound does not exclude intracranial structural pathology.

OBJECTIVE: To report the prenatal diagnosis and management of 34 fetuses with various intracranial structural pathologies diagnosed following a normal second-trimester ultrasound examination. METHODS: We retrospectively reviewed the images of 203 abnormal central nervous system ultrasound examinations performed between 13 and 37 weeks of gestation at our prenatal diagnosis unit. In 34 (16.7%) of them at least one previous second-trimester ultrasound examination had been performed and considered normal. These 34 fetuses represent the study group. RESULTS: The following intracranial pathologies were diagnosed: dysgenesis of the corpus callosum, ventriculomegaly, cerebral cysts or hemorrhage, migrational disorders, vermian dysgenesis, arachnoid cysts, macrocephaly, enlarged subarachnoid space, brain calcifications and microcephaly. CONCLUSION: A normal second-trimester ultrasound scan does not rule out significant intracranial anomalies. Parents and physicians should be informed about the limitations of second-trimester sonography as far as brain diagnosis is concerned. A repeat third-trimester scan may enable more accurate diagnosis and counseling.

Brain↗
PubMed2002

Congenital periventricular pseudocysts: prenatal sonographic appearance and clinical implications.

OBJECTIVE: Periventricular pseudocysts (PVPC) are diagnosed in approximately 1% of premature newborns that undergo brain sonography during the first 24 h of life. These pseudocysts are thought to develop antenatally due to germinal matrix hemorrhage, but have not been described until now in prenatal ultrasound studies. The aim of this study was to report the identification, differential diagnosis, and prognosis of PVPC detected by prenatal ultrasound examination. DESIGN: Between 1997 and 2001 we made an ultrasound diagnosis of PVPC in 11 fetuses. In nine fetuses the findings were characteristic of PVPC and these patients represent our study group. Fetal magnetic resonance imaging was performed in five patients. Termination of pregnancy was carried out in three patients, in one case intrauterine fetal death occurred at 31 weeks, and one infant died in the neonatal period. The surviving four newborns are being followed in the pediatric neurology clinic. RESULTS: PVPC were diagnosed by ultrasound scan in fetuses between 16 and 37 weeks of gestation (mean, 29.7 weeks). Magnetic resonance imaging confirmed the presence of PVPC in two cases. In eight cases the pseudocysts were unilateral and in one case bilateral. They were an isolated finding in five patients. Four of these fetuses were delivered at term and have normal neurological development at ages ranging from 6 to 25 months. All fetuses with additional pathologies (coarctation of the aorta, hemimegalencephaly, cytomegalovirus infection, hypoplasia of the vermis with dysmorphism) did not survive. CONCLUSIONS: The prenatal diagnosis of PVPC warrants an extensive search for possible associated pathological findings. As an isolated finding, antenatal PVPC seem to carry a good prognosis.

Abortion, Induced↗
PubMed2002

White matter abnormalities in Leber's hereditary optic neuropathy due to the 3460 mitochondrial DNA mutation.

Leber's hereditary optic neuropathy is a maternally inherited disorder characterized by acute or subacute loss of central vision leading to severe optic atrophy. It is caused by mutations in the mitochondrial genome. Primary mutations are located at nucleotide positions 3460, 11778 and 14484 in genes encoding subunits of complex I of the respiratory chain. The occurrence of a demyelinating disease such as multiple sclerosis has been reported mainly in females with the 11778 mutation. We report a patient with Leber's hereditary optic neuropathy, kyphosis and white matter lesions in association with the 3460 mtDNA mutation. It is suggested that multiple sclerosis-like illness and deformities of the vertebral column may be associated pathogenically with Leber's hereditary optic neuropathy.

Adolescent↗