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ABSTRACT: OBJECTIVE: To evaluate if a standard complete anatomical fetal survey, as recommended based on ultrasound (US) examination guidelines was feasible using a standardized MRI protocol. METHODS: Based on guidelines for US-based examination, we built up a specific MRI protocol for fetal anatomical survey. This protocol was then prospectively tested in 100 women, at a median gestational age (GA) of 30 weeks, undergoing fetal MRI examination for various specific indications. Ability to perform fetal anatomical survey was analysed by two reviewers (A and B) based on 26 predefined anatomical criteria agreed upon yielding a score ranging from 0 to 26 (complete anatomical study). Reproducibility was analysed using percentage of agreement and modified Kappa statistics. RESULTS: Mean (SD) [range] score for standardized anatomical survey was 24.6/26 (1.4) [15;26] and 24.2/26 (1.7) [15;26] according to A and B respectively (p=0.1). Satisfactory examination was achievable in >95%, 80-95% and <80% for 22, 2 and 2 and for 19, 4 and 3 anatomic criteria according to A and B respectively. For both reviewers, the two most difficult criteria to evaluate were aorta and pulmonary artery. Inter-reviewers agreement was above 90% for 22 of the 26 anatomical criteria and adjusted kappa coefficients for each criterion demonstrated good, moderate and poor agreement for 22, 2 and 2 criteria respectively. CONCLUSION: Our data support the hypothesis that standardized fetal anatomical examination might be achieved and reproducible using MRI even though further effort should aim at improving fetal cardiac examination.
Ultrasound in Obstetrics and Gynecology 01/2013; · 3.01 Impact Factor
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C Thauvin-Robinet,
S Thomas,
M Sinico,
B Aral,
L Burglen,
N Gigot,
H Dollfus,
S Rossignol,
M Raynaud,
C Philippe, [......],
N Elkhartoufi,
L Faivre,
A Munnich, N Boddaert,
L Van Maldergem,
F Encha-Razavi,
S Lyonnet,
M Vekemans,
E Escudier,
T Attié-Bitach
Clinical Genetics 10/2012; · 3.13 Impact Factor
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ABSTRACT: The most common clinical sign of autism spectrum disorders (ASD) is social interaction impairment, which is associated with communication deficits and stereotyped behaviors. Based on brain-imaging results, our hypothesis is that abnormalities in the superior temporal sulcus (STS) are highly implicated in ASD. These abnormalities are characterized by decreased grey matter concentration, rest hypoperfusion and abnormal activation during social tasks. STS anatomofunctional anomalies occurring early across brain development could constitute the first step in the cascade of neural dysfunctions underlying autism. It is known that STS is highly implicated on social perception processing, from perception of biological movements, such as body movements or eye gaze, to more complex social cognition processes. Among the impairments that can be described in social perception processing, eye gaze perception is particularly relevant in autism. Gaze abnormalities can now be objectively measured using eye-tracking methodology. In the present work, we will review recent data on STS contributions to normal social cognition and its implication in autism, with particular focus on eye gaze perception.
Revue Neurologique 09/2012; 168(10):762-70. · 0.49 Impact Factor
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A Brassier,
C Ottolenghi, N Boddaert,
P Sonigo,
T Attié-Bitach,
A-E Millischer-Bellaiche,
G Baujat,
V Cormier-Daire,
V Valayannopoulos,
N Seta,
M Piraud,
B Chadefaux-Vekemans,
C Vianey-Saban,
R Froissart,
P de Lonlay
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ABSTRACT: Inherited metabolic diseases are mostly due to enzyme deficiency in one of numerous metabolic pathways, leading to absence of a compound downstream from and the accumulation of a compound upstream from the deficient metabolite(s). Diseases of intoxication by proteins (aminoacidopathies, organic acidurias, urea cycle defects) and by sugars (galactosemia, fructosemia) usually do not give prenatal symptoms since mothers protect their fetuses from pathological metabolite accumulation. A well-known exception is hypoplasia of corpus callosum, as is sometimes observed in nonketotic hyperglycinemia and sulfite oxidase deficiency. Conversely, women with phenylketonuria "poison" their fetus if they are not treated (spontaneous abortions, intrauterine growth restriction [IUGR], cardiac malformations, and brain disease). Amino acid synthesis defects can lead to prenatal symptoms: microcephaly in serine deficiency (detectable by amino acid analysis in fetal cord blood), and brain malformations in glutamine synthetase deficiency. Impaired folate metabolism is involved in a large fraction of neurodevelopmental defects referred to as spina bifida, yet the underlying genetic component(s) are largely unknown. Energy metabolism diseases caused by defects in the synthesis or utilization of relevant metabolites lead to organ dysfunctions or malformations, but prenatal diagnosis is usually impossible unless genetic analysis can rely on a previously affected child in the family. A somewhat intermediate condition is defects of mitochondrial beta-oxidation of fatty acids, as they may sometimes be symptomatic prenatally (notably the HELLP syndrome or other presentations), and in this case, organic acid and acylcarnitine analysis in amniotic fluid can be informative in the absence of an index case. In contrast, complex molecule diseases commonly give prenatal symptoms that may permit the diagnosis even in the absence of index cases: hydrops fetalis and skeletal anomalies in lysosomal storage diseases, hydrops fetalis in congenital disorders of glycosylation (CDG) and transaldolase deficiency, brain malformations in O-glycosylation defects, brain malformations, kidney cysts and skeletal anomalies in peroxysomal diseases (Zellweger syndrome), syndactyly, genitalia malformations, and IUGR in Smith-Lemli-Opitz (SLO) syndrome. Although many metabolic disorders show biochemical abnormalities during fetal development that are informative for prenatal diagnosis, only a fraction of them are clinically/sonographically symptomatic before birth, thus allowing for prenatal diagnosis in the absence of an index case, i.e., serine deficiency, some fatty acid beta-oxidation defects, transaldolase deficiency, lysosomal diseases, CDG, Zellweger syndrome, and SLO syndrome.
Archives de Pédiatrie 08/2012; 19(9):959-69. · 0.30 Impact Factor
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Journal of Neuroradiology 05/2012; · 1.21 Impact Factor
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ABSTRACT: Understanding of brain structural anomalies seen in children with autism has considerably progressed since the apparition of MRI and functional imaging. All the results are converging toward the description of anatomical and functional anomalies in the regions of the so-called "social brain". Statistical analyses show diminution of gray matter in the region of the superior temporal sulcus (STS). Functional studies with PET shows a diminution of brain blood flow at rest in the same region. Brain activation studies show absence of activation of the specialized region in processing human voice and hypoactivation of "social brain" regions in complex tasks of social cognition. At last, abnormal connectivity between the frontal and temporal regions has been showed. Those regions are implicated in processing sensorial inputs necessary for normal social life. All those anomalies could be responsible of the abnormal social behaviour pattern of children with autism.
Archives de Pédiatrie 04/2012; 19(5):547-50. · 0.30 Impact Factor
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ABSTRACT: Percutaneous sclerotherapy is an effective treatment for aneurysmal bone cysts (ABCs).
The purpose of this study was to demonstrate the safety and efficacy of sclerotherapy with absolute alcohol and to propose a vascular classification of ABCs based on a retrospective review.
This was a review of children treated with absolute alcohol sclerotherapy for ABC at a single institution from January 1995 until November 2009. Treatment response was evaluated radiographically and clinically. Cyst fluid was classified as clear, partially bloody, or bloody. Presence of any venous drainage of the cyst was assessed by injection of contrast medium into the cyst cavity.
Twenty-nine children with ages ranging from 2 to 16 years were included. Treatment response was good in 17 (59%), partial in 9 (31%), and poor in 3 (10%) children. Venous drainage was absent in six out of seven clear-fluid cysts, which we classified as lymphatic. Drainage was present in all seven bloody-fluid cysts, which we classified as venous. In seven partially bloody-fluid cysts, venous drainage was seen in three.
Sclerotherapy with absolute alcohol is a safe and effective treatment of ABC. We propose classifying ABC as lymphatic or venous and suggest considering ABC intraosseous slow-flow vascular malformations.
Pediatric Radiology 01/2012; 42(5):599-605. · 1.67 Impact Factor
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ABSTRACT: NBIA characterizes a class of neurodegenerative diseases that feature a prominent extrapyramidal movement disorder, intellectual deterioration, and a characteristic deposition of iron in the basal ganglia. The diagnosis of NBIA is made on the basis of the combination of representative clinical features along with MR imaging evidence of iron accumulation. In many cases, confirmatory molecular genetic testing is now available as well. A number of new subtypes of NBIA have recently been described, with distinct neuroradiologic and clinical features. This article outlines the known subtypes of NBIA, delineates their clinical and radiographic features, and suggests an algorithm for evaluation.
American Journal of Neuroradiology 09/2011; 33(3):407-14. · 2.93 Impact Factor
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A S Lebre,
M Rio,
L Faivre d'Arcier,
D Vernerey,
P Landrieu,
A Slama,
C Jardel,
P Laforêt,
D Rodriguez,
N Dorison, [......],
B Funalot,
N Villeneuve,
V Valayannopoulos,
P de Lonlay,
I Desguerre,
F Brunelle,
J P Bonnefont,
A Rötig,
A Munnich, N Boddaert
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ABSTRACT: To identify a consistent pattern of brain MRI imaging in primary complex I deficiency. Complex I deficiency, a major cause of respiratory chain dysfunction, accounts for various clinical presentations, including Leigh syndrome. Human complex I comprises seven core subunits encoded by mitochondrial DNA (mtDNA) and 38 core subunits encoded by nuclear DNA (nDNA). Moreover, its assembly requires six known and many unknown assembly factors. To date, no correlation between genotypes and brain MRI phenotypes has been found in complex I deficiencies.
The brain MRIs of 30 patients carrying known mutation(s) in genes involved in complex I were retrospectively collected and compared with the brain MRIs of 11 patients carrying known mutations in genes involved in the pyruvate dehydrogenase (PDH) complex as well as 10 patients with MT-TL1 mutations.
All complex I deficient patients showed bilateral brainstem lesions (30/30) and 77% (23/30) showed anomalies of the putamen. Supratentorial stroke-like lesions were only observed in complex I deficient patients carrying mtDNA mutations (8/19) and necrotising leucoencephalopathy in patients with nDNA mutations (4/5). Conversely, the isolated stroke-like images observed in patients with MT-TL1 mutations, or the corpus callosum malformations observed in PDH deficient patients, were never observed in complex I deficient patients.
A common pattern of brain MRI imaging was identified with abnormal signal intensities in brainstem and subtentorial nuclei with lactate peak as a clue of complex I deficiency. Combining clinico-biochemical data with brain imaging may therefore help orient genetic studies in complex I deficiency.
Journal of Medical Genetics 10/2010; 48(1):16-23. · 6.36 Impact Factor
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L Galmiche,
F Jaubert,
F Sauvat,
S Sarnacki,
O Goulet,
Z Assouline,
V Vedrenne,
A-S Lebre, N Boddaert,
N Brousse,
D Chrétien,
A Munnich,
A Rötig
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ABSTRACT: Chronic intestinal pseudo-obstruction (CIPO) is a severe disease of the digestive tract motility. In pediatric population, CIPO remains of unknown origin for most patients. Chronic intestinal pseudo-obstruction is also a common feature in the course of mitochondrial oxidative phosphorylation disorders related for some patients to mutations in TYMP, POLG1, mtDNA tRNA(leu(UUR)) or tRNA(lys) genes. We hypothesized that CIPOs could be the presenting symptom of respiratory chain enzyme deficiency and thus we investigated oxidative phosphorylation in small bowel and/or colon smooth muscle of primary CIPO children.
We studied eight children with CIPO and 12 pediatric controls. We collected clinical, radiological and pathological data and measured respiratory chain enzymatic activity in isolated smooth muscle of the small bowel and/or the colon. We also sequenced TYMP, POLG, mtDNA tRNA(leu(UUR)) and tRNA(lys) genes.
Neither pathological nor radiological data were in favor of a mitochondrial dysfunction. No respiratory chain enzyme deficiency was detected in CIPO children. In myogenic CIPO, respiratory enzymes and citrate synthase activities were increased in small bowel and/or colon whereas no abnormality was noted in neurogenic and unclassified CIPO. Levels of enzyme activities were higher in control small bowel than in control colon muscle. Sequencing of TYMP, POLG, mtDNA tRNA(leu(UUR)) and tRNA(lys) genes and POLG gene did not reveal mutation for any of the patients.
The normal enzymatic activities as the lack of radiological and genetic abnormalities indicate that, at variance with adult patients, oxidative phosphorylation deficiency is not a common cause of childhood CIPO.
Neurogastroenterology and Motility 09/2010; 23(1):24-9, e1. · 3.41 Impact Factor
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M Rio,
A S Lebre,
P de Lonlay,
V Valayannopoulos,
I Desguerre,
J-L Dufier,
D Grévent,
M Zilbovicius,
C Tréguier,
F Brunelle,
C de Baracé,
J Kaplan,
M A Espinase-Berrod,
C Sainte-Rose,
S Puget,
A Rotig,
A Munnich, N Boddaert
Neurology 07/2010; 75(1):93. · 8.31 Impact Factor
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ABSTRACT: Stem cell transplantation is not appropriate first-line treatment for attenuated phenotypes of mucopolysaccharidosis type I (MPS I). In three patients with attenuated MPSA I treated by laronidase, Patients 2 and 3 displayed significant cognitive improvement within 2years; Patients 1 and 3 displayed improvement on MRI scans of the brain.
Molecular Genetics and Metabolism 05/2010; 100(1):20-3. · 3.19 Impact Factor
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N Boddaert,
I Desguerre,
N Bahi-Buisson,
S Romano,
V Valayannopoulos,
Y Saillour,
D Seidenwurm,
D Grevent,
L Berteloot,
A-S Lebre,
M Zilbovicius,
S Puget,
R Salomon,
T Attie-Bitach,
A Munnich,
F Brunelle,
P de Lonlay
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ABSTRACT: OBJECTIFS: To propose a MRI cerebellar algorithm that may be applied to guide genetic/malformative or biochemical investigations for patients with cerebellar ataxia.
Cerebral MRI of 158 patients with cerebellar ataxia and no supratentorial abnormality were examined according to a new categorization system based on posterior fossa imaging. The clinical and radiological findings were confronted to biochemical and/or genetic results using the MR cerebellar algorithm. Seven groups of cerebellar MRI pattern were described: vermian dysgenesis (n=27), cerebellar hypoplasia (n=15), hemispheric cerebellar dysgenesis (n=6), unilateral hemispheric atrophy (n=5), global cerebellar atrophy (n=84), signal abnormalities (n=11) and normal MRI (n=10). Cerebellar hypoplasia, vermian dysgenesis and hemispheric cerebellar dysgenesis groups were classified as malformative disorders. Global atrophy and signal abnormality groups were classified as metabolic disorders.
In the vermian dysgenesis group, a specific genetic diagnosis was obtained in eight children (8/27) and all of the mutated genes (AHI1 (JBS3), CEP290 (JBS5), TMEM67 (JBS6), and RPGRIP1L (JBS7)) are involved in primary cilia function. In the group of pontocerebellar hypoplasia specific genetic diagnosis was obtained in one patient (PCH2) (1/15). Thus, nine of 42 children classified as malformative disorder had a molecular diagnosis. Global atrophy and signal abnormality groups were classified as metabolic disorders, specific biochemical was obtained in 46/95 children. In global atrophy group, respiratory chain deficiency was diagnosed in 18 children (18/84). In 21 children a congenital disorders of glycosylation type 1a (CDG Ia) was diagnosed (21/84) and infantile neuroaxonale dystrophy (INAD) was diagnosed in one child. In signal abnormalities group, specific biochemical diagnosis was obtained in six out of 11 children, five children with respiratory chain deficiency and one child with sulphite oxidase deficiency. In hemispheric cerebellar dysgenesis and normal MRI groups, no biological diagnosis was found for any of the patients. In the group of unilateral hemispheric atrophy, we hypothesized a clastic prenatal injury.
The proposed MR cerebellar algorithm was useful to guide genetic/malformative or biochemical investigations, allowing an etiological diagnosis in 55 children.
Journal of Neuroradiology 04/2010; 37(4):220-30. · 1.21 Impact Factor
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ABSTRACT: Although status epilepticus (SE) affects the course of Dravet syndrome (DS), it rarely alters dramatically psychomotor outcome. We report an unusual pattern in 3 patients who following refractory SE lasting respectively 2, 7 and 12h experienced persistent and severe cognitive and motor deterioration. We compared these patients to published data and to personal experience in Necker hospital, to find links between severe outcome and clinical features such as treatment or duration of refractory SE. The key point was that anoxoischemic-like lesions appeared on MRI although cardiovascular function had remained stable. Therefore, neither hemodynamic failure, nor abnormalities of cardiac rhythm could explain the lesions and neurological worsening. For theoretical reasons the responsibility of therapy common for the 3 patients, e.g., barbiturates was suspected.
Seizure 02/2010; 19(3):190-4. · 1.80 Impact Factor
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F Molinari,
A Kaminska,
G Fiermonte, N Boddaert,
A Raas-Rothschild,
P Plouin,
L Palmieri,
F Brunelle,
F Palmieri,
O Dulac,
A Munnich,
L Colleaux
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ABSTRACT: Neonatal epileptic encephalopathies with suppression bursts (SBs) are very severe and relatively rare diseases characterized by neonatal onset of seizures, interictal electroencephalogram (EEG) with SB pattern and very poor neurological outcome or death. Their etiology remains elusive but they are occasionally caused by metabolic diseases or malformations. Studying an Arab Muslim Israeli consanguineous family, with four affected children presenting a severe neonatal epileptic encephalopathy, we have previously identified a mutation in the SLC25A22 gene encoding a mitochondrial glutamate transporter. In this report, we describe a novel SLC25A22 mutation in an unrelated patient born from first cousin Algerian parents and presenting severe epileptic encephalopathy characterized by an EEG with SB, hypotonia, microcephaly and abnormal electroretinogram. We showed that this patient carried a homozygous p.G236W SLC25A22 mutation which alters a highly conserved amino acid and completely abolishes the glutamate carrier's activity in vitro. Comparison of the clinical features of patients from both families suggests that SLC25A22 mutations are responsible for a novel clinically recognizable epileptic encephalopathy with SB.
Clinical Genetics 08/2009; 76(2):188-94. · 3.13 Impact Factor
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V Valayannopoulos, N Boddaert,
K Mention,
G Touati,
V Barbier,
A Chabli,
F Sedel,
J Kaplan,
J L Dufier,
David Seidenwurm,
D Rabier,
J M Saudubray,
P de Lonlay
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ABSTRACT: Ornithine delta-aminotransferase (OAT) deficiency causes gyrate atrophy (GA) of the retina, as a consequence of high plasma ornithine concentrations. Because creatine synthesis requires the conversion of arginine and glycine into ornithine and guanidinoacetate, high ornithine concentration inhibits this reaction thus causing secondary creatine deficiency. The aim of this study was to evaluate the neuropsychological features and creatine metabolism in patients with GA.
The study involved 7 GA patients, aged from 11 to 27 years who underwent neuropsychological evaluation and cerebral proton magnetic resonance spectroscopy (MRS).
Neurocognitive impairment was found in 5/7 patients, including mental retardation (3/7), school failure (1/7), major visuospatial dyspraxia (1/7), aggressive behavior (3/7) and epilepsy (2/7). Two patients had normal neuropsychological evaluation. Cerebral proton magnetic resonance spectroscopy revealed a profound creatine deficiency in all patients. MRS data were confirmed by decreased levels of creatine and/or guanidinoacetate in plasma and urine in all patients.
In our group of patients with GA, we found a high prevalence of neurological impairment, not reported so far, and possibly related to secondary creatine deficiency and hyperornithinemia. We propose to treat mentally retarded GA patients with high doses of creatine, as it may normalize brain creatine levels and help to reduce ornithine levels.
Molecular Genetics and Metabolism 04/2009; 97(2):109-13. · 3.19 Impact Factor
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M A Cosson,
J F Benoist,
G Touati,
M Déchaux,
N Royer,
L Grandin,
J P Jais, N Boddaert,
V Barbier,
I Desguerre,
P M Campeau,
D Rabier,
V Valayannopoulos,
P Niaudet,
P de Lonlay
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ABSTRACT: To better delineate the natural history of patients with methylmalonic aciduria (MMA).
Thirty patients with vitamin-B12-unresponsive MMA (25 aged 1.5 to 22.0 years (y) at the end of the study and 5 who died during a metabolic crisis) were managed following standardized guidelines and studied retrospectively. The median follow-up was 8.3 y (range: 1.4-19.5). Patients were investigated with neuropsychological testing, brain MRIs, inulin clearances, biochemical and genetic studies.
Fifteen patients had a neonatal onset. Thirteen patients (43%) had significant neurological impairment. Chronic renal disease (CRD) occurred in 14 patients (47%) with a median age of onset of 6.5 y (range 1.5-18.6). Renal function further deteriorated in 4 patients within a median period of 5.8 y (range 2-7.4). Of 25 patients investigated at the enzymatic level, 17 were classified mut(o), 3 mut- and 5 cblA. Mortality, number of acute decompensations (p=0.031), median MMA urinary excretion (p=0.006) and neurological impairment (p<0.0001) were higher in mut degrees patients compared to mut-/cblA patients. Concerning the CRD, no difference incidence was found although the onset of CRD occurred earlier in mut(o) patients and was more severe.
Our study provides unique data concerning the progression of renal disease in MMA. Patients with mut(o) phenotype have a more severe phenotype and probably an earlier and more severe CRD than patients with mut-/cblA phenotype.
Molecular Genetics and Metabolism 03/2009; 97(3):172-8. · 3.19 Impact Factor
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N. Brahimi,
M. Jambou,
E. Sarzi,
V. Serre, N. Boddaert,
S. Romano,
P. de Lonlay,
A. Slama,
A. Munnich,
A. Rötig,
J.P. Bonnefont,
A.S. Lebre
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ABSTRACT: Deoxyguanosine kinase (dGK) deficiency is a frequent cause of mitochondrial DNA depletion associated with a hepatocerebral phenotype. In this study, we describe a new splice site mutation in the DGUOK gene and the clinical, radiologic, and genetic features of these DGUOK patients. This new DGUOK homozygous mutation (c.444-62C>A) was identified in three patients from two North-African consanguineous families with combined respiratory chain deficiencies and mitochondrial DNA depletion in the liver. Brain MRIs are normal in DGUOK patients in the literature. Interestingly, we found subtentorial abnormal myelination and moderate hyperintensity in the bilateral pallidi in our patients. This new mutation creates a cryptic splice site in intron 3 (in position −62) and is predicted to result in a larger protein with an in-frame insertion of 20 amino acids. In silico analysis of the putative impact of the insertion shows serious clashes in protein conformation: this insertion disrupts the α5 helix of the dGK kinase domain, rendering the protein unable to bind purine deoxyribonucleosides. In addition, a common haplotype that segregated with the disease in both families was detected by haplotype reconstruction with 10 markers (microsatellites and SNPs), which span 4.6 Mb of DNA covering the DGUOK locus. In conclusion, we report a new DGUOK splice site mutation that provide insight into a critical protein domain (dGK kinase domain) and the first founder mutation in a North-African population.
Molecular Genetics and Metabolism 03/2009; · 3.19 Impact Factor
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Archives de Pédiatrie 07/2008; 15(5):711-2. · 0.30 Impact Factor
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N Bahi-Buisson, N Boddaert,
Y Saillour,
I Souville,
K Poirier,
P-L Léger,
L Castelnau,
P Plouin,
N Carion,
C Beldjord,
J Chelly
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ABSTRACT: Malformations of cortical development (MCD) represent a major cause of developmental disabilities and severe epilepsy. Advances in imaging and genetics have improved the diagnosis and classification of these conditions. Up to now, eight genes have been involved in different types of MCD. Lissencephaly-pachygyria and subcortical band heterotopia (SBH) represent a malformative spectrum resulting from mutations of either LIS1 or DCX genes. LIS1 mutations cause a more severe malformation in the posterior brain regions. DCX mutations usually cause anteriorly predominant lissencephaly in males and SBH in female patients. Additional forms are X-linked lissencephaly with corpus callosum agenesis and ambiguous genitalia associated with mutations of the ARX gene. Lissencephaly with cerebellar hypoplasia (LCH) encompass heterogeneous disorders named LCH type a to d. LCHa are related with mutation in LIS1 or DCX, LCHb with mutation of RELN gene, and LCHd could be related with TUBA1A gene. Polymicrogyria encompass a wide range of clinical, aetiological and histological findings. Among several syndromes, recessive bilateral fronto-parietal polymicrogyria has been associated with mutations of the GPR56 gene. Bilateral perisylvian polymicrogyria showed a linkage to chromosome Xq28 in some pedigrees, and mutations in SRPX2 gene in others conditions. X-linked bilateral periventricular nodular heterotopia (BPNH) consists of BPNH with focal epilepsy in females and prenatal lethality in males. Filamin A (FLNA) mutations have been reported in some families and in sporadic patients. It is possible to infer the most likely causative gene by brain imaging studies and other clinical findings. Based on this experience, a detailed phenotype analysis is needed to develop the most efficient research on MCD in the future.
Revue Neurologique 07/2008; 164(12):995-1009. · 0.49 Impact Factor
