French guidelines for the diagnosis and management of Tourette syndrome.

The term "Gilles de la Tourette syndrome", or the more commonly used term "Tourette syndrome" (TS) refers to the association of motor and phonic tics which evolve in a context of variable but frequent psychiatric comorbidity. The syndrome is characterized by the association of several motor tics and at least one phonic tic that have no identifiable cause, are present for at least one year and appear before the age of 18. The presence of coprolalia is not necessary to establish or rule out the diagnosis, as it is present in only 10% of cases. The diagnosis of TS is purely clinical and is based on the symptoms defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). No additional tests are required to confirm the diagnosis of TS. However, to exclude certain differential diagnoses, further tests may be necessary. Very frequently, one or more psychiatric comorbidities are also present, including attention deficit hyperactivity disorder, obsessive-compulsive disorder, anxiety, explosive outbursts, self-injurious behaviors, learning disorders or autism spectrum disorder. The condition begins in childhood around 6 or 7 years of age and progresses gradually, with periods of relative waxing and waning of tics. The majority of patients experience improvement by the end of the second decade of life, but symptoms may persist into adulthood in around one-third of patients. The cause of TS is unknown, but genetic susceptibility and certain environmental factors appear to play a role. The treatment of TS and severe forms of tics is often challenging and requires a multidisciplinary approach (involving the general practitioner (GP), pediatrician, psychiatrist, neurologist, school or occupational physicians, psychologist and social workers). In mild forms, education (of young patients, parents and siblings) and psychological management are usually recommended. Medical treatments, including antipsychotics, are essential in the moderate to severe forms of the disease (i.e. when there is a functional and/or psychosocial discomfort linked to tics). Over the past decade, cognitive-behavioral therapies have been validated for the treatment of tics. For certain isolated tics, botulinum toxin injections may also be useful. Psychiatric comorbidities, when present, often require a specific treatment. For very severe forms of TS, treatment by deep brain stimulation offers real therapeutic hope. If tics are suspected and social or functional impairment is significant, specialist advice should be sought, in accordance with the patient's age (psychiatrist/child psychiatrist; neurologist/pediatric neurologist). They will determine tic severity and the presence or absence of comorbidities. The GP will take over the management and prescription of treatment: encouraging treatment compliance, assessing side effects, and combating stigmatization among family and friends. They will also play an important role in rehabilitation therapies, as well as in ensuring that accommodations are made in the patient's schooling or professional environment.

Dermatological and genetic data in tuberous sclerosis: A prospective single-center study of 38 patients.

BACKGROUND: Tuberous sclerosis complex (TSC) is a genetic disorder involving the TSC1 or TSC2 gene. Skin signs are prominent, but dermatological data are scarce. This study aims to describe the cutaneous signs of TSC with the genotype. METHODS: We studied the dermatological characteristics of 38 patients with TSC at the University Hospital of Montpellier. We collected details of genotypic features. RESULTS: All the patients presented at least one cutaneous sign. The dermatological examination alone was sufficient to establish a definite diagnosis of TSC based on the diagnostic criteria for 34/38 patients. No association was found between cutaneous signs and the presence of a TSC1 or TSC2 mutation. We noted skin signs that were poorly described in the disease, namely epidermal nevus in 3 patients, vascular malformation in 2 patients, and keratosis pilaris in 9 patients. DISCUSSION: While several studies demonstrate a more severe neurological phenotype in TSC2 mutated patients, skin expression does not appear to differ according to the mutated gene. Further case reports and molecular genetic studies are needed to determine the link between epidermal nevus, vascular malformations, keratosis pilaris and TSC.

Deciphering the natural history of SCA7 in children.

BACKGROUND AND PURPOSE: Childhood-onset autosomal dominant cerebellar ataxia type 7 (SCA7) is a severe disease which leads to premature loss of ambulation and death. Early diagnosis of SCA7 is of major importance for genetic counselling and still relies on specific genetic testing, driven by clinical expertise. However, the precise phenotype and natural history of paediatric SCA7 has not yet been fully described. Our aims were to describe the natural history of SCA7 in a large multicentric series of children of all ages, and to find correlates to variables defining this natural history. METHODS: We collected and analysed clinical data from 28 children with proven SCA7. All had clinical manifestations of SCA7 and either a definite number of CAG repeats in ATXN7 or a long expansion > 100 CAG. RESULTS: We identified four clinical presentation patterns related to age at onset. Children of all age groups had cerebellar atrophy and retinal dystrophy. Our data, combined with those in the literature, suggest that definite ranges of CAG repeats determine paediatric SCA7 subtypes. The number of CAG repeats inversely correlated to all variables of the natural history. Age at gait ataxia onset correlated accurately to age at loss of walking ability and to age at death. CONCLUSION: SCA7 in children has four presentation patterns that are roughly correlated to the number of CAG repeats. Our depiction of the natural history of SCA7 in children may help in monitoring the effect of future therapeutic trials.

Ketone Bodies as a Possible Adjuvant to Ketogenic Diet in PDHc Deficiency but Not in GLUT1 Deficiency.

OBJECTIVE: Ketogenic diet is the first line therapy for neurological symptoms associated with pyruvate dehydrogenase deficiency (PDHD) and intractable seizures in a number of disorders, including GLUT1 deficiency syndrome (GLUT1-DS). Because high-fat diet raises serious compliance issues, we investigated if oral L,D-3-hydroxybutyrate administration could be as effective as ketogenic diet in PDHD and GLUT1-DS. METHODS: We designed a partial or total progressive substitution of KD with L,D-3-hydroxybutyrate in three GLUT1-DS and two PDHD patients. RESULTS: In GLUT1-DS patients, we observed clinical deterioration including increased frequency of seizures and myoclonus. In parallel, ketone bodies in CSF decreased after introducing 3-hydroxybutyrate. By contrast, two patients with PDHD showed clinical improvement as dystonic crises and fatigability decreased under basal metabolic conditions. In one of the two PDHD children, 3-hydroxybutyrate has largely replaced the ketogenic diet, with the latter that is mostly resumed only during febrile illness. Positive direct effects on energy metabolism in PDHD patients were suggested by negative correlation between ketonemia and lactatemia (r 2 = 0.59). Moreover, in cultured PDHc-deficient fibroblasts, the increase of CO2 production after 14C-labeled 3-hydroxybutyrate supplementation was consistent with improved Krebs cycle activity. However, except in one patient, ketonemia tended to be lower with 3-hydroxybutyrate administration compared to ketogenic diet. CONCLUSION: 3-hydroxybutyrate may be an adjuvant treatment to ketogenic diet in PDHD but not in GLUT1-DS under basal metabolic conditions. Nevertheless, ketogenic diet is still necessary in PDHD patients during febrile illness.

[Bilateral facial nerve palsy associated with Epstein-Barr virus infection in a 3-year-old boy]. / Paralysie faciale bilatérale au cours d'une infection à virus d'Epstein­Barr.

Bilateral facial nerve palsy is a rare and sometimes difficult diagnosis. We describe a case of bilateral simultaneous facial nerve palsy associated with Epstein-Barr virus (EBV) infection in a 3-year-old boy. Several symptoms led to the diagnosis of EBV infection: the clinical situation (fever, stomachache, and throat infection), white blood cell count (5300/mm3 with 70% lymphocyte count), seroconversion with EBV-specific antibodies, lymphocytic meningitis, and a positive blood EBV polymerase chain reaction (9.3×103 copies of EBV-DNA). An MRI brain scan showed bilateral gadolinium enhancement of the facial nerve. A treatment plan with IV antibiotics (ceftriaxone) and corticosteroids was implemented. Antibiotics were stopped after the diagnosis of Lyme disease was ruled out. The patient's facial weakness improved within a few weeks. Bilateral facial nerve palsy is rare and, unlike unilateral facial palsy, it is idiopathic in only 20% of cases. Therefore, it requires further investigation and examination to search for the underlying etiology. Lyme disease is the first infectious disease that should be considered in children, especially in endemic areas. An antibiotic treatment effective against Borrelia burgdorferi should be set up until the diagnosis is negated or confirmed. Further examination should include a blood test (such as immunologic testing, and serologic testing for viruses and bacterium with neurological tropism), a cerebrospinal fluid test, and an MRI brain scan to exclude any serious or curable underlying etiology. Facial bilateral nerve palsy associated with EBV is rarely described in children. Neurological complications have been reported in 7% of all EBV infections. The facial nerve is the most frequently affected of all cranial nerves. Facial palsy described in EBV infections is bilateral in 35% of all cases. The physiopathology is currently unknown. Prognosis is good most of the time.

Chronic Diarrhea in L-Amino Acid Decarboxylase (AADC) Deficiency: A Prominent Clinical Finding Among a Series of Ten French Patients.

Aromatic L-amino acid decarboxylase (AADC) deficiency is an autosomal recessive inborn error of metabolism, affecting catecholamines and serotonin biosynthesis. Cardinal signs consist in psychomotor delay, hypotonia, oculogyric crises, dystonia, and extraneurological symptoms. PATIENTS AND METHODS: We present a retrospective descriptive multicentric study concerning ten French children with a biochemical and molecular confirmed diagnosis of AADC deficiency. RESULTS: Clinical presentation of most of our patients was consistent with the previous descriptions from the literature (hypotonia (nine children), autonomic signs (nine children), sleep disorders (eight children), oculogyric crises (eight children), motor disorders like hypertonia and involuntary movements (seven children)). We described however some phenotypic particularities. Two patients exhibited normal intellectual abilities (patients already described in the literature). We also underlined the importance of digestive symptoms like diarrhea, which occurred in five among the ten patients. We report in particular two children with chronic diarrhea, complicated by severe failure to thrive. Vanillactic acid (VLA) elevation in urines of one of these two patients led to suspect the diagnosis of AADC deficiency, as in two other patients from our population. CONCLUSION: Some symptoms like chronic diarrhea were atypical and have been poorly described in the literature up to now. Diagnosis of the AADC deficiency is sometimes difficult because of the phenotypic heterogeneity of the disease and VLA elevation in urines should suggest the diagnosis.

[Mitochondrial neurogastrointestinal encephalopathy disease]. / L'encéphalomyopathie neuro-gastro-intestinale mitochondriale : un tableau d'anorexie mentale atypique.

Mitochondrial neurogastrointestinal encephalopathy disease (MNGIE) is a rare autosomal-recessive syndrome, resulting from mutations in the TYMP gene, located at 22q13. The mutation induces a thymidine phosphorylase (TP) deficit, which leads to a nucleotide pool imbalance and to instability of the mitochondrial DNA. The clinical picture regroups gastrointestinal dysmotility, cachexia, ptosis, ophthalmoplegia, peripheral neuropathy, and asymptomatic leukoencephalopathy. The prognosis is unfavorable. We present the case of a 14-year-old Caucasian female whose symptoms started in early childhood. The diagnosis was suspected after magnetic resonance imaging (MRI), performed given the atypical features of mental anorexia, which revealed white matter abnormalities. She presented chronic vomiting, postprandial abdominal pain, and problems gaining weight accompanied by cachexia. This diagnosis led to establishing proper care, in particular an enteral and parenteral nutrition program. There is no known specific effective treatment, but numerous studies are in progress. In this article, after reviewing the existing studies, we discuss the main diagnostic and therapeutic aspects of the disease. We argue for the necessity of performing a cerebral MRI given the atypical features of a patient with suspected mental anorexia (or when the clinical pattern of a patient with mental anorexia seems atypical), so that MNGIE can be ruled out.

Partial acute transverse myelitis is a predictor of multiple sclerosis in children.

BACKGROUND: Acute transverse myelitis (ATM) in children is a rare and often severe disease for which there are few known prognostic factors, particularly the subsequent risk of multiple sclerosis (MS) diagnosis. OBJECTIVES: To determine the clinical course and prognostic factors after a first episode of ATM in children. METHODS: Thirty children below 16 years of age diagnosed with a first neurological episode of ATM were included retrospectively. Clinical evaluation, treatment, laboratory, and MRI data were collected. RESULTS: Median age at onset was 11 years (range 3-15 years). Follow-up data were available for a median of 4 years (range 0.5-16.7 years). Five patients subsequently had a diagnosis of MS (17%), which was associated with acute partial transverse myelitis (odds ratio 5; 95% confidence interval 2.3-11), with a 60% probability of having a relapse at five years (p < 0.01). The 2011 Verhey criteria correctly identified MS in children with the highest specificity (96%) and sensitivity (80%). CONCLUSION: Acute partial transverse myelitis and brain MRI abnormalities at initial presentation are significantly predictive of a subsequent diagnosis of MS in children with ATM. These findings suggest that closer brain MRI monitoring after acute partial transverse myelitis might make the earlier introduction of disease-modifying therapies possible.

Treatment for dystonia in childhood.

Management of childhood dystonia differs in certain respects from that of adult dystonia: (i) childhood dystonia is more often secondary than primary; (ii) mixed motor disorders are frequent; (iii) in children, the course of dystonia may be influenced by ongoing brain maturation and by the remarkable plasticity of the young brain; (iv) drug tolerability and effectiveness can be different in children; (v) the therapeutic strategy must be discussed with both the patient and his or her parents; and (vi) the child's education must be taken into account. Based on a systematic review of the literature through June 2011 and on our personal experience, we propose a therapeutic approach to childhood dystonia. After a detailed clinical evaluation and a comprehensive work-up to rule out a treatable cause of dystonia, symptomatic treatment may include various drugs, local botulinum toxin injections, and deep brain stimulation, in addition to rehabilitation.

[Genetic syndromes that mimic congenital infections: report of 2 cases]. / Syndromes génétiques mimant les infections congénitales : à propos de 2 cas.

Genetic syndromes that mimic congenital infections must be recognized because of the associated risk of recurrence. We describe a male infant who was born with the association of intra-uterine growth retardation, microcephaly, intracranial calcifications, white matter abnormalities, microphtalmy, bilateral cataract, and hearing loss. Congenital cytomegalovirus (CMV) infection was suspected, but serologic CMV markers were not decisive (IgG+/IgM-). His half-sister (same father) presented a similar phenotype. Therefore, the diagnosis of congenital CMV infection was questioned and a genetic hypothesis was suggested. In 1983, Baraitser et al. first described two brothers with microcephaly and intracranial calcifications and negative TORCH analysis. Later, a number of authors reported children in whom detailed investigation failed to objectively confirm an intra-uterine infective agent. Clinical features include severe postnatal microcephaly, seizures, and pronounced developmental arrest. These cases have been considered to define a distinct autosomal recessive disorder first named pseudo-Torch syndrome. The family described herein is different from the cases previously described with a suspected autosomal dominant inheritance, severe ophtalmological abnormalities, and unusual brain imaging.

[Neonatal seizures management]. / Prise en charge des crises du nouveau-né

For several decades, experimental studies have sought to explain the biological causes of newborn seizures and to assess the anatomical and functional consequences. Laboratory studies have shown that prolonged or repeated seizures disturb central nervous system development and may predispose to later epilepsy or cognitive deficits. Although these findings have not been clinically demonstrated in humans, several observations suggest that neonatal seizures have a deleterious effect on the immature brain and generate long-term sequelae. No therapeutic trial, however, has directly demonstrated the benefits of treatment, underlining the need for controlled studies that integrate the advances in electroencephalographic monitoring and pharmacology of anticonvulsant drugs.

[Acute inflammatory polyradiculoneuropathy and membranous glomerulonephritis following Epbstein-Barr virus primary infection in a 12-year-old girl]. / Polyradiculonévrite aiguë et glomérulonéphrite extramembraneuse au décours d'une primo-infection à Epstein-Barr virus chez une patiente de 12 ans.

Acute inflammatory polyradiculoneuropathy, or Guillain-Barré syndrome (GBS), is characterized by peripheral nerve demyelination, which leads to rapidly progressive weakness, loss of sensation, and loss of deep tendon reflexes. It is a prototype of postinfectious autoimmune disease, whose pathophysiology is well described in the forms provoked by certain bacteria (molecular mimicry with Campylobacter jejuni), but remains unclear for the forms related to other organisms (cytomegalovirus, Epstein-Barr virus and other herpes group viruses, Mycoplasma pneumoniae). Glomerular lesions can be associated with the neurological symptoms and have also been described after various infections, independently of any signs of polyradiculoneuropathy. We report the observation of a 12-year-old girl who presented with Guillain-Barré syndrome with facial diplegia, ataxia, and intracranial hypertension following Epstein-Barr virus (EBV) primary infection. During the course of the neurological disease, membranous glomerulonephritis (MGN) was diagnosed. The neurological impairment was regressive within 6 months after intravenous immunoglobulin treatment followed by intravenous then oral corticosteroid administration. Viremia remained high more than 6 months after the onset of symptoms. Glomerulopathy progressed independently and finally required immunosuppressant medication with cyclosporine. EBV might be the factor that triggered the autoimmune disorders, as previously reported for systemic lupus erythematosus and multiple sclerosis in children. To the best of our knowledge, this association of 3 conditions (GBS, MGN, and EBV primary infection) has never been reported in the literature.

[Treatment of childhood dystonia]. / Traitement des dystonies de l'enfant.

Dystonia is not uncommon in childhood, but is clinically very heterogeneous. Therefore, introduction and follow-up of the treatment of dystonia in children are often a challenge for the physicians. Progresses in functional neurosurgery have open new fields in the treatment of dystonia in children, but it should be managed by a multidisciplinary team. This paper reviews the various therapeutic options available for childhood-onset dystonia, with a specific attention to dosage and side effects of the drugs regarding pediatric population according to the data of the literature. The rational strategy for therapeutic management of the various types of childhood dystonia is discussed.

[New developments in spastic unilateral cerebral palsy]. / Hémiplégie cérébrale infantile: épidémiologie, aspects étiologiques et développements thérapeutiques récents.

INTRODUCTION: Hemiplegic (or spastic unilateral) cerebral palsy accounts for about 30% of all cases of cerebral palsy. With a population prevalence of 0.6 per 1000 live births, it is the most common type of cerebral palsy among term-born children and the second most common type after diplegia among preterm infants. STATE OF THE ART: Many types of prenatal and perinatal brain injury can lead to congenital hemiplegia and brain MRI is the most useful tool to classify them with accuracy and to provide early prognostic information. Perinatal arterial ischemic stroke thus appears as the leading cause in term infants, whereas encephalopathy of prematurity is the most common cause in premature babies. Other causes include brain malformations, neonatal sinovenous thrombosis, parenchymal hemorrhage (for example due to coagulopathy or alloimmune thrombocytopenia) and the more recently described familial forms of porencephaly associated with mutations in the COL4A1 gene. PERSPECTIVES: In adjunction with pharmacologic treatment (botulinium neurotoxin injection), new evidence-based rehabilitational interventions, such as constraint-induced movement therapy and mirror therapy, are increasingly being used.

[Acute motor deficit in childhood: diagnosis management]. / Déficit moteur aigu non traumatique de l'enfant : orientations diagnostiques.

Acute motor deficit is not uncommon in childhood, with various neurological etiologies. Pertinent semiological analysis allows correct diagnosis management, with adequate paraclinical investigations. The authors describe this clinical diagnosis strategy. The most common clinical situations and various etiologies are presented; paraclinical investigations confirming the diagnosis are discribed, with specific attention to central nervous system imaging according to the most recent sequences.

Unexpected neurological sequelae following propofol anesthesia in infants: Three case reports.

UNLABELLED: Propofol is a widely used hypnotic agent for induction and maintenance of pediatric anesthesia with a well known safety profile. Experimental in vitro studies suggest that propofol may be toxic to developing neurons. We report the cases of three infants who underwent surgery before 2 months of age for different benign pathologies. Propofol was used for induction and maintenance of anesthesia in all cases. The three patients developed convulsions with similar clinical characteristics (cluster of recurrent clinical and subclinical seizures) between the 23th and 30th hours following anesthesia. Clinical and electroencephalographic improvement was obtained between the third and fourth day of management in pediatric intensive care unit. The seizures never recurred, and the three patients underwent further uneventful general anesthesia without propofol. Follow-up of the three patients disclosed unexpected neurological dysfunction: progressive microcephaly (head circumferences were normal at birth), developmental impairment with cognitive and behavioural disturbances in two cases, and bilateral symmetrical white-matter abnormalities on cerebral magnetic resonance imaging. CONCLUSION: The causal relationship between propofol anesthesia and the neurological symptoms of our patients remains difficult to ascertain, but we believe that pediatricians, anesthetists and intensive care-givers should be aware of this possible adverse reaction that has never been described before.

[Monogenetic dystonia: revisiting the dopaminergic hypothesis]. / Dystonies monogéniques: l'hypothèse dopaminergique revisitée.

Dystonias are clinically and genetically heterogeneous neurological disorders that affect movement, and are the focus of much investigative work. The recent identification of mutations in the gene THAP1 in DYT6 dystonia reopens the very interesting question of the in fine involvement of dopamine in the different types of dystonia. In this review, we will go through the recent literature in order to evaluate the many contributions to this theory as well as to highlight the difficulties in identifying a global regulatory pathway for the different forms of this disease that we are just starting to decipher.

Mutational spectrum of CDKL5 in early-onset encephalopathies: a study of a large collection of French patients and review of the literature.

The CDKL5 gene has been implicated in the molecular etiology of early-onset intractable seizures with infantile spasms (IS), severe hypotonia and atypical Rett syndrome (RTT) features. So far, 48 deleterious alleles have been reported in the literature. We screened the CDKL5 gene in a cohort of 177 patients with early-onset seizures, including 30 men and 10 girls with Aicardi syndrome. The screening was negative for all men as well as for women with Aicardi syndrome, excluding the CDKL5 gene as a candidate for this neurodevelopmental disorder. We report 11 additional de novo mutations in CDKL5 in female patients. For the first time, the MLPA approach allowed the identification of a partial deletion encompassing the promoter and the first two exons of CDKL5. The 10-point mutations consist of five missenses (with recurrent amino acid changes at p.Ala40 and p.Arg178), four splicing variants and a 1-base pair duplication. We present a review of all mutated alleles published in the literature. In our study, the overall frequency of mutations in CDKL5 in women with early-onset seizures is around 8.6%, a result comparable with previous reports. Noteworthy, the CDKL5 mutation rate is high (28%) in women with early-onset seizures and IS.

[Paroxysmal kinesigenic dyskinesia: a channelopathy? Study of 19 cases]. / Les dyskinésies paroxystiques kinésigéniques : une << canalopathie >> ? Etude de 19 cas.

INTRODUCTION: Paroxysmal kinesigenic dyskinesia (PKD) is characterized by brief episodes of dystonia and choreoathetosis triggered by sudden voluntary movements. Disease onset is seen in the first or second decade. The attacks typically last less than one minute. Three autosomal dominant PKD loci are identified: EKD1, EKD2 and EKD3. EKD1 has an overlap with the locus of the "Infantile Convulsion and Choreoathetosis (ICCA) syndrome". The favorable natural history, the episodic nature of the symptoms and their sensitivity to anticonvulsant therapy suggest channelopathy as a mechanism of PKD. PATIENTS AND METHODS: We reviewed the clinical features, the family history, the treatment response, the evolution and the technical investigations in 19 affected individuals. RESULTS: All cases were idiopathic. Ten patients had a positive familial history. Three patients suffered from ICCA syndrome. Some atypical features were seen, such as the association of kinesigenic and nonkinesigenic attacks and the presence of migraine, ataxia, seizures and myoclonus. Acetazolamide responsiveness was seen in two patients. CONCLUSION: The coexistence of PKD and nonkinesigenic dyskinesia in several patients confirms the earlier described presence of intermediary forms, nonrepresented in the current classification of paroxysmal dyskinesias. Our study results suggest channel dysfunction and basal ganglia involvement in the pathophysiology of PKD.

Refinement of cortical dysgeneses spectrum associated with TUBA1A mutations.

OBJECTIVE: We have recently shown that de novo mutations in the TUBA1A gene are responsible for a wide spectrum of neuronal migration disorders. To better define the range of these abnormalities, we searched for additional mutations in a cohort of 100 patients with lissencephaly spectrum for whom no mutation was identified in DCX, LIS1 and ARX genes and compared these data to five previously described patients with TUBA1A mutations. RESULTS: We detected de novo TUBA1A mutations in six patients and highlight the existence of a prominent form of TUBA1A related lissencephaly. In four patients, the mutations identified, c.1190T>C (p.L397P), c.1265G>A (p.R422H), c.1264C>T (p.R422C), c.1306G>T (p.G436R), have not been reported before and in two others, the mutation corresponds to a recurrent missense mutation, c.790C>T (p.R264C), likely to be a hot spot of mutation. All together, it emerges that the TUBA1A related lissencephaly spectrum ranges from perisylvian pachygyria, in the less severe form, to posteriorly predominant pachygyria in the most severe, associated with dysgenesis of the anterior limb of the internal capsule and mild to severe cerebellar hypoplasia. When compared with a large series of lissencephaly of other origins (ILS17, ILSX or unknown origin), these features appear to be specific to TUBA1A related lissencephaly. In addition, TUBA1A mutated patients share a common clinical phenotype that consists of congenital microcephaly, mental retardation and diplegia/tetraplegia. CONCLUSIONS: Our data highlight the presence of consistent and specific abnormalities that should allow the differentiation of TUBA1A related lissencephalies from those related to LIS1, DCX and ARX genes.