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Biomedical subjects

G Ponsot

Publications and source records attributed to G Ponsot.

At least 73 records · Page 4Linked to original sources
PubMed1995

[Subcortical laminal heterotopia and lissencephaly: cerebral malformations of X-linked inheritance].

Subcortical laminar heterotopia (band heterotopia) is a brain malformation now recognized by MRI. We report 3 families (2 previously described) in which several members had subcortical laminar heterotopia or a more severe malformation (agyria/pachygyria). In these families, subcortical laminar heterotopia were observed in women and were associated with epilepsy or slight mental retardation depending on the extend of heterotopia. Males had lissencephaly with refractory epilepsy and severe mental retardation. The pedigrees of these families demonstrate that these 2 malformations originate from a single genetic origin. A single X-linked dominant gene is postulated. Diagnosis of subcortical laminar heterotopia in a female or lissencephaly in a male (except in the case of Miller-Dieker syndrome) requires appropriate genetic counselling in the family: brain imaging should be performed in relatives.

Adult↗
PubMed1995

Opercular malformations: clinical and MRI features in 11 children.

Opercular malformations are rare and complex brain malformations for which only very fragmented neuropathological descriptions have been reported. They are related to an abnormal development of both sylvian fissure and frontoparietal operculum. We report a retrospective clinical and MRI study of 11 patients presenting with opercular malformations. A congenital pseudobulbar syndrome was observed in six cases, various motor disorders in seven cases, mental retardation in six cases and epilepsy in four cases. The purpose of this study is to evaluate the main features of opercular malformations in children and to try to characterise this entity on the basis of its clinical features and MRI pattern.

Cerebral Cortex↗
PubMed1994

Is Rett syndrome a chromosome breakage syndrome?

Lymphocytes from venous blood from 15 girls with Rett syndrome (RTS), 7 girls with RTS "forme fruste," and 46 unrelated control females were examined. All subjects had a normal karyotype using RHG and RTBG technique. The frequency of gaps and breaks was determined for each group. A significantly higher (P < 0.01) frequency of chromosome breakage was observed in RTS subjects compared to controls. This work suggests that an increased tendency to chromosome breakage may be part of a genetically determined disorder in RTS patients.

Case-Control Studies↗
PubMed1994

Reappraisal of Rasmussen's syndrome with special emphasis on treatment with high doses of steroids.

Eight patients with Rasmussen's syndrome and epilepsia partialis continua were treated with high doses of steroids, including pulses of methylprednisolone and prednisone in decreasing doses. Three patients exhibited clinical, radiological, or histological evidence of bilateral involvement. Epilepsy and focal deficit decreased within six months in seven patients. Only five patients, in whom steroid treatment had begun less than 15 months after the onset of epilepsia partialis continua, experienced a lasting effect although they had periodic episodes of transient relapse. Treatment with high doses of steroids seems advisable during the first year after onset of epilepsia partialis continua, before hemiplegia has developed and in cases with bilateral involvement.

Adolescent↗
PubMed1994

Aberrant splicing of exon 6 in the pyruvate dehydrogenase-E1 alpha mRNA linked to a silent mutation in a large family with Leigh's encephalomyelopathy.

Pyruvate dehydrogenase (PDH)-E1 alpha deficiency has recently been studied at the molecular-genetic level. The gene is situated on the X chromosome. We report on an unusual mutation in a familial E1 alpha deficiency. In fibroblasts, PDH deficiency was diagnosed in a young infant presenting with Leigh's encephalomyelopathy and in a maternal nephew with episodes of "malaises." In the two affected children as well as their mothers we found a silent mutation in exon 6 of the PDH-E1 alpha and an aberrant splicing of exon 6 in some of the cDNA clones. This case emphasizes the need for both genomic and cDNA analysis in cases where a PDH-E1 alpha deficiency is strongly suspected.

Base Sequence↗
PubMed1994

Genetic heterogeneity of familial hemiplegic migraine.

Familial hemiplegic migraine (FHM) is an autosomal dominant variety of migraine with aura. We previously mapped a gene responsible for this disorder to the short arm of chromosome 19, within a 30-cM interval bracketed by D19S216 and D19S215. Linkage analysis conducted on two large pedigrees did not show any evidence of heterogeneity, despite their clinical differences due to the presence, in one family, of cerebellar ataxia and nystagmus. Herein we report linkage data on seven additional FHM families including another one with cerebellar ataxia. Analysis was conducted with a set of seven markers spanning the D19S216-D19S215 interval. Two-point and multipoint lod score analyses as well as HOMOG testing provided strong evidence for genetic heterogeneity. Strong evidence of linkage was obtained in two families and of absence of linkage in four families. The posterior probability of being of the linked type was > .95 in the first two families and < .01 in four other ones. It was not possible to draw any firm conclusion for the last family. Thus, within the nine families so far tested, four were linked, including those with associated cerebellar ataxia. We could not find any clinical difference between the pure FHM families regardless of whether they were linked. In addition to the demonstration of genetic heterogeneity of FHM, this study also allowed us to establish that the most likely location of the gene was within an interval of 12 cM between D19S413 and D19S226.

Ataxia↗
PubMed1993

Verbal and visual memory impairment in children with epilepsy.

Verbal and visual memory performances were evaluated in 60 epileptic children and 60 normal control subjects with Signoret's Memory Battery scale. Eighteen patients had idiopathic generalized epilepsy and 42 had partial epilepsy, mostly of the temporal (n = 28) and frontal (n = 10) lobes. Memory scores were statistically lower in epileptics than in controls and significant differences were found within each group: (1) children with idiopathic generalized epilepsy had a slight depression of visual memory; (2) memory disorder was more severe in partial epilepsy; and (3) children with left and right temporal lobe epilepsy had marked memory deficits related to hemispheric specialization.

Adolescent↗
PubMed1993

E1 pyruvate dehydrogenase deficiency in a child with motor neuropathy.

We report the case of a boy who developed a motor neuropathy during infectious episodes at 18 mo and 3 y of age. When he was 7 y old, he suffered persistent weakness and areflexia; his resting lactate and pyruvate values were 3.65 mM and 398 microM, respectively (controls: 1.1 +/- 0.3 mM and 90 +/- 22 microM), and an exercise test demonstrated a lactic acidosis (13.6 mM; controls: 6.4 +/- 1.3 mM) with a high pyruvate level (537 microM; controls: 176 +/- 15 microM) and a low lactate/pyruvate ratio (24.2; controls: 35 +/- 2). The results of polarographic studies on muscle mitochondria suggested a defect in pyruvate oxidation (pyruvate 17 ng atom O/min/mg protein; controls: 115 +/- 42), whereas glutamate, palmitoylcarnitine, and succinate were good respiratory substrates. The activity of total pyruvate dehydrogenase complex (PDHC) in muscle mitochondria and in fresh mononuclear cells was markedly decreased (9.7 and 0.054 nmol 14CO2/min/mg protein, respectively; controls: 123 +/- 4.5 and 0.733 +/- 0.03, respectively). Immunochemical analysis in muscle mitochondria demonstrated an absence of the alpha and beta E1 PDHC subunits. After 2 y of treatment with 500 mg/d thiamine, the patient was clinically improved. A genetic study of the main regions of mutations (exon 10 and 11) in the X chromosome encoding for the E1 alpha subunit of PDHC did not show any mutation. These data indicate that, although genetically different, this case enters in a very rare category of patients with PDHC deficiency without cerebral dysfunction and improved by thiamine + L-carnitine therapy.

Base Sequence↗
PubMed1993

[Biotinidase deficiency. Progressive encephalopathy curable with biotin].

BACKGROUND: Multiple carboxylase deficiency is a rare cause of progressive encephalopathy. There are 2 forms: the neonatal-onset form of holocarboxylase synthetase deficiency and the late-onset form of biotinidase deficiency. This report describes a case of biotinidase deficiency. CASE REPORT: A boy began to have repeated convulsions at the age of 3 months. The brain CT-scan and MRI were normal and the patient was given valproic acid and carbamazepine. Progressive neurological degradation was noted from the 4th month of life and myoclonic seizures began 2 months later. At admission, the patient had seizures, myoclonic fits and hypotonia. He had a skin rash but no alopecia. Biochemical investigation showed lactic acidosis, mainly in the CSF, moderate hyperammonemia and hyperalaninemia. Chromatography of organic acids showed several abnormal peaks suggesting biotinidase deficiency. The patient was given biotin (20 mg/day) orally. This treatment produced a pronounced, rapid, clinical and biochemical improvement and antiepileptic drugs were discontinued. There was no developmental delay at the age of 18 months. CONCLUSION: The clinical findings of neurologic abnormalities and dermatological signs led to the diagnosis of a metabolic disease that, fortunately, can be treated. This disease could benefit from a mass neonatal screening program.

Amidohydrolases↗
PubMed1993

[Herpes encephalitis in newborn infants. Retrospective study of 12 cases].

BACKGROUND: Herpes simplex virus (HSV) may cause severe disease in neonates with high mortality and devastating sequelae. Adenine arabinoside (ara-A) and acyclovir can be effective in treating the neonatal disseminated disease, but optimal doses of the drugs are still debated. PATIENTS: The files of 12 neonates treated for HSV infection between May 1983 and April 1989 in 9 departments of pediatrics were studied. The following data were analysed: age at initial signs, clinical manifestations, CSF abnormalities, viral and immunological studies, imaging techniques used to detect brain damage, doses and duration of treatment. RESULTS: The mean age at the first infectious signs was 12.3 +/- 9.3 days and neurological manifestations were first seen at 18.3 +/- 7.7 days. Acyclovir was given intravenously for 2 to 4 weeks at doses of 30 mg/kg/24 hr (5 patients) or 60 mg/kg/24 hr (7 patients) at an average of 7.7 days after the first clinical manifestations. The initial dose of 30 mg/kg/24 hr was increased to 50 or 60 mg/kg/24 hr in 3 patients. Five patients died during treatment, and 5 had severe sequelae; follow-up for the 2 remaining patients was not possible. There was no correlation between prognosis and the dose of acyclovir, which was well tolerated in all patients. CONCLUSIONS: The best results are obtained when treatment is started early. This retrospective study failed to show any dose-dependent difference in the efficacy of acyclovir. A prospective study with different doses would be useful.

Acyclovir↗
PubMed1993

[Acquired cerebral toxoplasmosis in an non-immunosuppressed child].

BACKGROUND: Postnatally acquired toxoplasmosis is relatively common as an unapparent infection. When there are severe clinical manifestations such as encephalitis, pneumonia and myocarditis, the patient should be checked for immunocompetence deficiencies. CASE REPORT: A two-year old girl living in French Guyana suffered from acute respiratory distress due to interstitial pneumonia plus pericarditis that was treated by closed pericardial aspiration. Palsies of four limbs and chorioretinitis gradually appeared. The CSF protein content was elevated, 1 g/l, but the number of cells was normal. Serologic tests indicated a recent toxoplasma infection; she was given sulfadoxine, pyrimethamine and spiramycin. Her neurologic condition and the persistent antibodies, indicating active disease, led to her transfer to our Department 3 months after the onset of the disease. The CSF contained 47 cells/mm3 and 0.8 g/l proteins. Measurement of both IgM and IgG classes of toxoplasma antibodies showed persistent high titers in the blood and CSF. The CT scan showed numerous calcifications in the brain and hypodense areas in the frontal and parietal lobes. The MRI showed extensive changes. The severity of the disease in this girl led us to study her immune system. It was normal. The girl was given 6-week treatments with pyrimethamine-sulfadiazine for 2 years. This treatment stabilized the disease, but her titers of toxoplasma antibodies remained high. CONCLUSION: The initial clinical presentation of the disease in this patient and persistent high titers of toxoplasma antibodies, especially of the IgM class, argue against the possibility of congenital toxoplasmosis and favor the diagnosis of acquired disease in a patient who has no immune deficiency.

Child, Preschool↗
PubMed1992

Segregation of three reciprocal translocations in the same family: t(3;4), t(5;10), and t(15;21).

A male infant with static antenatal encephalopathy and epilepsy was found to have a duplication of 5p12----5pter and deficiency of 10p13----10pter. Each of his parents was a carrier of a balanced reciprocal translocation. A third translocation was found in the maternal grandfather. The pedigree of each translocation and the segregation of parental reciprocal translocations are discussed.

Amino Acids↗
PubMed1992

Kearns-Sayre syndrome with sideroblastic anemia: molecular investigations.

The progressive syndrome of Kearns-Sayre has been studied at the clinical, biochemical and genetic levels in a patient. Clinical arguments suggest an evolution from Pearson's disease to Kearns-Sayre syndrome. The respiratory chain activities were low, and Southern blot analysis, together with gene sequencing, showed a heteroplasmic deletion of 7767 base pairs in a significant proportion of the mitochondrial DNA in different tissues. Protein synthesis studies on lymphoblasts did not reveal any translation of the new reading frame created by the deletion, although the corresponding deleted mitochondrial DNA sequence is transcribed.

Anemia, Sideroblastic↗
PubMed1991

Different mechanisms inferred from sequences of human mitochondrial DNA deletions in ocular myopathies.

We have sequenced the deletion borders of the muscle mitochondrial DNA from 24 patients with heteroplasmic deletions. The length of these deletions varies from 2.310 bp to 8.476 bp and spans from position 5.786 to 15.925 of the human mitochondrial genome preserving the heavy chain and light chain origins of replication. 12 cases are common deletions identical to the mutation already described by other workers and characterized by 13 bp repeats at the deletion boundaries, one of these repeats being retained during the deletion process. The other cases (10 out of 12) have shown deletions which have not been previously described. All these deletions are located in the H strand DNA region which is potentially single stranded during mitochondrial DNA replication. In two cases, the retained Adenosine from repeat closed to the heavy strand origin of replication would indicate slippage mispairing. Furthermore in one patient two mt DNA molecules have been cloned and their sequences showed the difference of four nucleotides in the breakpoint of the deletion, possibly dued to slippage mispairing. Taken together our results suggest that deletions occur either by slippage mispairing or by internal recombination at the direct repeat level. They also suggest that different mechanisms account for the deletions since similarly located deletions may display different motives at the boundaries including the absence of any direct repeat.

Base Sequence↗