De novo mutations in GRIN1 cause extensive bilateral polymicrogyria.

Polymicrogyria is a malformation of cortical development. The aetiology of polymicrogyria remains poorly understood. Using whole-exome sequencing we found de novo heterozygous missense GRIN1 mutations in 2 of 57 parent-offspring trios with polymicrogyria. We found nine further de novo missense GRIN1 mutations in additional cortical malformation patients. Shared features in the patients were extensive bilateral polymicrogyria associated with severe developmental delay, postnatal microcephaly, cortical visual impairment and intractable epilepsy. GRIN1 encodes GluN1, the essential subunit of the N-methyl-d-aspartate receptor. The polymicrogyria-associated GRIN1 mutations tended to cluster in the S2 region (part of the ligand-binding domain of GluN1) or the adjacent M3 helix. These regions are rarely mutated in the normal population or in GRIN1 patients without polymicrogyria. Using two-electrode and whole-cell voltage-clamp analysis, we showed that the polymicrogyria-associated GRIN1 mutations significantly alter the in vitro activity of the receptor. Three of the mutations increased agonist potency while one reduced proton inhibition of the receptor. These results are striking because previous GRIN1 mutations have generally caused loss of function, and because N-methyl-d-aspartate receptor agonists have been used for many years to generate animal models of polymicrogyria. Overall, our results expand the phenotypic spectrum associated with GRIN1 mutations and highlight the important role of N-methyl-d-aspartate receptor signalling in the pathogenesis of polymicrogyria.

Whole-exome sequencing reveals a novel missense mutation in the MARS gene related to a rare Charcot-Marie-Tooth neuropathy type 2U.

Charcot-Marie-Tooth (CMT) is a heterogeneous group of progressive disorders, characterized by chronic motor and sensory polyneuropathy. This hereditary disorder is related to numerous genes and varying inheritance patterns. Thus, many patients do not reach a final genetic diagnosis. We describe a 13-year-old girl presenting with progressive bilateral leg weakness and gait instability. Extensive laboratory studies and spinal magnetic resonance imaging scan were normal. Nerve conduction studies revealed severe lower limb peripheral neuropathy with prominent demyelinative component. Following presumptive diagnosis of chronic inflammatory demyelinating polyneuropathy, the patient received treatment with steroids and intravenous immunoglobulins courses for several months, with no apparent improvement. Whole-exome sequencing revealed a novel heterozygous c.2209C>T (p.Arg737Trp) mutation in the MARS gene (OMIM 156560). This gene has recently been related to CMT type 2U. In-silico prediction programs classified this mutation as a probable cause for protein malfunction. Allele frequency data reported this variant in 0.003% of representative Caucasian population. Family segregation analysis study revealed that the patient had inherited the variant from her 60-years old mother, reported as healthy. Neurologic examination of the mother demonstrated decreased tendon reflexes, while nerve conduction studies were consistent with demyelinative and axonal sensory-motor polyneuropathy. Our report highlights the importance of next-generation sequencing approach to facilitate the proper molecular diagnosis of highly heterogeneous neurologic disorders. Amongst other numerous benefits, this approach might prevent unnecessary diagnostic testing and potentially harmful medical treatment.

Frequency of pediatric migraine with aura in a clinic-based sample.

OBJECTIVE: To assess the prevalence and risk factors for pediatric migraine with aura (MWA) among patients presenting to pediatric neurology clinics. BACKGROUND: Headache is a common complaint among children, and the prevalence of migraine is about 8%. Up to one third of adults with migraine report experiencing aura; however, the exact percentage in children is unknown. METHODS: Medical records of children presenting with headache to three pediatric neurology clinics in Haifa in the last 5 years were retrospectively reviewed. Inclusion criteria were a diagnosis of migraine headache at 5-18 years of age. RESULTS: Of 260 children (140 female) who had migraine, 26.2% experienced aura. MWA was more common among females compared to males (32.6% vs 18.9%, P < .01) and among older children (OR: 2.50, 95% CI: 1.20-5.20; P < .01). Among those who experienced aura, visual aura was more common in females than males (66.7% vs 33.3%, P < .04). Family history of migraine was strongly related to MWA (P < .02): the odds of MWA were 2.46 times greater in children who had a family history of migraine. (OR: 2.46, 95% CI: 1.08-5.62; P < .03). CONCLUSIONS: MWA is as common in children as in adults. Aura is more common in older children. Children who have MWA are more likely to have a family history of migraine.

Clinical Profile of Attention Deficit Hyperactivity Disorder: Impact of Ethnic and Social Diversities in Israel.

BACKGROUND: Despite the increased worldwide recognition of attention deficit/hyperactivity disorder (ADHD), there is a variability in the diagnostic rate of both ADHD and its co-morbidities. These diversities are probably related to the methodology and instruments used for the diagnosis of ADHD and to awareness and cultural interpretation of its existence. OBJECTIVES: To identify consistent differences in the clinical profile of Arab and Jewish children with ADHD in Israel who differ in cultural, ethnic and socioeconomic background. METHODS: We analyzed the data of 823 children and adolescents with ADHD (516 Jews and 307 Arabs) and compared the clinical characteristics between these two ethnic groups. All patients were evaluated in two neuropediatric and child development centers in northern Israel: one in Haifa and one in Hadera. Children with autism and intellectual disabilities were excluded. RESULTS: The distribution of ADHD subtypes was similar in both populations. However, learning disorders and psychiatric co-morbidities (behavioral difficulties and anxiety) were reported more frequently in the Jewish population. The most commonly reported adverse effects to psychostimulants were mood changes, anorexia, headache, insomnia and rebound effect, and were more frequently reported in the Jewish population (42.0% vs.18.0%, P < 0.05). CONCLUSIONS: We assume that these differences are related to cultural and socioeconomic factors. We suggest that the physician take cultural background into consideration when treating patients with ADHD.

Pediatric mixed headache -The relationship between migraine, tension-type headache and learning disabilities - in a clinic-based sample.

BACKGROUND: Headache is a common complaint among children. The most common primary headache syndromes in childhood are migraine and TTH. However many times they seem to overlap. The purpose of our study was to assess the relationship between pediatric migraine, tension-type headache (TTH) and learning disabilities. METHODS: Children presenting with headache to three pediatric neurology clinics in the last 5 years were assessed. Two hundred sixty-two children, 5-18 years of age, who met the criteria for migraine were included. RESULTS: Of 262 children (54 % female) who had migraine, 26.2 % had migraine with aura. 59 children (22.5 % of the full sample) reported also having headaches that met the criteria for episodic TTH/mixed headaches. Females were more than 2.8 times more likely to experience mixed headaches than males (OR: 2.81, 95 % CI: 1.43-5.54; p <.003). Multiple logistic regression analysis revealed that older age (p <0.02), family history of aura (p <.02), and (lack of) TTH (p <.003) were significant predictors of aura, whereas gender was not significant (p >0.20). Children who had migraine with aura were less likely to have mixed headaches than children who did not have aura (OR: 0.26, 95 % CI: 0.11-0.63; p <.003). Children with mixed headaches were 2.7 times more likely to have a learning disability than children with migraine alone. CONCLUSIONS: Episodic TTH and migraine without aura (mixed headaches) in children might be part of a continuum, which can explain the high incidence of their co-occurrence as opposed to migraine with aura. Children with mixed headaches have a higher incidence of learning disability compare to those with migraine alone.

The Clinical Characteristics of ADHD Diagnosed in Adolescents in Comparison With Younger Children.

Objective: The aim of this study is to identify the clinical characteristics in adolescents newly diagnosed with ADHD. Method: Data of patients aged 7 to 17 years diagnosed with ADHD were collected and analyzed. The patients were divided into adolescents aged 13 to 17 years (Group I) and children aged 7 to 12 years (Group II): 592 males and 231 females. Group I consists of 450 participants, and Group II consists of 373 participants. Results: Adolescents were predominantly inattentive (63.8%); most of Group II patients had combined or hyperactive ADHD (70.8%). Learning disorders were more common in adolescents (51.2% vs. 39.7%) and treated mainly with long-acting methylphenidate (MPH), and Group II patients were treated mainly with short- and medium-acting MPH. Newly diagnosed adolescents were less likely to exhibit behavioral comorbidities. Headache and insomnia were reported more in adolescents, and stimulant rebound effect was more in younger children. Conclusion: Although the biological nature of ADHD is similar in both age groups, the primary symptomatology and associated comorbidities are prone to age-dependent changes.

Pseudotumor Cerebri Syndrome: From Childhood to Adulthood Risk Factors and Clinical Presentation.

INTRODUCTION: Although considered uncommon, pseudotumor cerebri syndrome (PTC) is a significant cause of headache among children and adults. However, the presenting symptoms may be different among diverse age groups. In the present study, we compared the risk factors and clinical presentation of PTC across life-from childhood to adulthood. METHODS: A retrospective survey of PTC patients aged 7 years or older between 2011 and 2013 was carried out. Pooled analyses were performed comparing characteristics from our data with those of published data subdivided into 3 age groups: pre-young children, adolescents, and adults. RESULTS: Our cohort consisted of 72 patients: 32 children (10 pre-young children, 22 adolescents) and 40 adults. Within the pre-young children age group: 20% were females versus 82% in the adolescent age group and 85% of the adult age group. Obesity was found in 10% of the young children group, 64% of the adolescents, and 80% of the adults. Headache was reported in 70% young children, 82% adolescents, and 83% adults. Pooled analysis of 1499 patients showed that young children with PTC tend to complain less about headache compared with older ones. Vomiting and visual impairment were most common among adolescents, and dizziness and tinnitus were most common in adults. CONCLUSION: PTC has different risk factors and clinical presentation throughout life. In young children, there is no gender preference and most patients are not obese. Risk factors in adolescents resemble those of adults.

Clinical spectrum and medical treatment of children with electrical status epilepticus in sleep (ESES).

PURPOSES: To describe the clinical spectrum and to evaluate the efficacy of different therapeutic agents in children with electrical status epilepticus in sleep (ESES). METHODS: Clinical data of all patients with ESES (not including patients with Landau-Kleffner syndrome) in four pediatric neurology outpatient clinics were analyzed. Thirty patients with ESES had been treated between 1994 and 2007. RESULTS: Eleven (37%) children had benign partial epilepsies of childhood, five (17%) had cerebral palsy, five (17%) had hydrocephalus, one (3%) had schizencephaly, one (3%) had prenatal parenchymal bleeding, and the etiology was unclear in seven (23%). The duration of ESES ranged between 2 and 60 months. The antiepileptic drugs that were found to be efficacious were: levetiracetam (41%), clobazam (31%), and sulthiame (17%). Valproic acid, lamotrigine, topiramate, and ethosuximide showed no efficacy. Steroids were efficacious in 65%; immunoglobulins were efficacious in 33%. High-dose diazepam was efficacious in 37%, but all the children had temporary response. Seventeen patients (57%) had cognitive deterioration, whereas the rest presented with regression in attention, speech, communication, and behavior. Fourteen children had permanent cognitive deficit. There was a significant correlation (p = 0.029) between the duration of ESES and residual intellectual deficit at follow-up. CONCLUSIONS: ESES reflects an evolution of benign partial epilepsy of childhood in more than one-third of the patients, whereas there is an underlying structural brain anomaly in another one-third. The most efficacious antiepileptic drugs (AEDs) are levetiracetam and clobazam. The duration of ESES correlated significantly with residual intellectual deficit at follow-up.

Delayed language development due to infantile thiamine deficiency.

The aim of this study was to investigate the language development of 20 children who had been exposed to thiamine (vitamin B(1)) deficiency in infancy due to feeding with soy-based formula that was accidentally deficient of thiamine. In this case-control study, 20 children (12 males, eight females; mean age 31.8mo [SD 4.1], range 24-39mo) who were fed thiamine-deficient formula in infancy were compared with 20 children (12 males, eight females; mean age 32.2mo [SD 3.9], range 25-39mo) fed with other milk sources and matched for age, sex, and maternal education. Receptive and expressive language development was assessed with the Preschool Language Scale, 3rd edition. Other assessments included mental development (Bayley Scales of Infant Development, 2nd edition), evaluation for autistic spectrum disorders, and neurological examination. Motor development was compared by age at independent walking. The study and control groups differed significantly in the expressive communication (p<0.001) and auditory comprehension language subscales (p<0.001), the Mental Developmental Index score (p<0.001), and age at independent walking (p=0.001). A significant correlation was found between the receptive language score and age at independent walking, i.e. poorer language associated with later walking (r=-0.601, p=0.005). The conclusion was that thiamine deficiency in infancy could affect language development in childhood.

Handedness in patients with developmental coordination disorder.

Developmental coordination disorder affects 5% to 8% of the general population, and about 50% to 60% of these children have a comorbid attention-deficit disorder with hyperactivity and learning disorders. Left-handedness is relatively common among children with dyslexia, learning disabilities, and autism; however, its frequency in children with developmental coordination disorder is less clear. The present study investigated the distribution of hand dominance in 98 children (age range, 5.5-17 years) with developmental coordination disorder compared with their parents or siblings. Thirty children (30.6%) were left-handed and 13 (13.3%) were ambidextrous. The prevalence of left-handedness among their parents and siblings was similar to that of the general population. The results suggest that children with developmental coordination disorder, like children with learning disorders and deficit disorder with hyperactivity, present with higher frequency of left-hand dominance compared with the general population.

Vigabatrin, lamotrigine, topiramate and serum carnitine levels.

Clinical studies indicate a decrease in free and total carnitine in children treated with old-generation antiepileptic drugs (especially valproate). Here, we studied the effect of new-generation antiepileptic drugs on serum carnitine levels. Serum carnitine levels were measured in 91 children: 24 treated with vigabatrin, 28 treated with lamotrigine, and 21 treated with topiramate. These drugs were given as monotherapy (54 children) or polytherapy (19 children). Eighteen additional children treated with valproate served as control subjects. Reduced mean serum carnitine level was evident only in children treated with valproate, with mean free and total carnitine level of 26.9 +/- 8.6 micromol/L and 29.1 +/- 10.4 micromol/L, respectively. In contrast, the mean serum carnitine levels of children treated with vigabatrin, lamotrigine, or topiramate were similar and normal. In these children, the free carnitine levels were 38.5 +/- 7.8 micromol/L, 37.2 +/- 7.7 microg/mL, and 40.4 +/- 8.7 micromol/L, respectively, and total carnitine levels were 43.5 +/- 8.8 micromol/L, 44.4 +/- 9.2 micromol/L, and 45.5 +/- 9.8 micromol/L (+/-S.D.), respectively. Only 4 children (treated with valproate) exhibited considerably lower serum carnitine levels. None of these children had significant clinical adverse effects attributable to carnitine deficiency. In conclusion, these new-generation antiepileptic drugs probably do not cause carnitine deficiency. In contrast, valproate may induce carnitine deficiency, but most cases are asymptomatic.

Typical absence epilepsy presenting prior to age of 3 years: an uncommon form of idiopathic generalized epilepsy.

PURPOSE: An attempt to allocate patients with the clinical features and electroencephalography (EEG) abnormalities of typical absence epilepsy presenting before the age of 3 years, similar to childhood and juvenile absence epilepsy (JAE) and delineate the clinical manifestations, EEG abnormalities, therapy and outcome of such an epileptic disorder by conducting a nationwide survey. RESULTS: Overall, eight infants, six males and two females, abided by the inclusion criteria of typical absence epilepsy: They were born after an unremarkable pregnancy and labor presenting at the age of 12-34 months (mean: 19.6 months) with frequent absences time-linked with an EEG demonstrating generalized occasionally irregular epileptiform discharges of 3-4 Hz spike/wave and normal background activity along with an electrographic photosensitive response in one patient. Neurological examination was intact in all infants. All eight infants were initially treated with valproic acid, of whom seven immediately responded and one had increase in frequency and duration of absences completely aborted with treatment of lamotrigine. Three relapsed after termination of therapy of whom two again presented with recurrent absences and another one with generalized tonic-clonic seizures and as such these children had virtually transformed into a later form of idiopathic generalized epilepsy (IGE) during childhood. All eight patients are seizure-free, seven still on therapy; seven children within a follow-up period of 2-7 years and the most recently diagnosed infant for 6 months. Cognitive skills were found normal in all children within the low normal range in three children with short attention and concentration spans. CONCLUSION: The data presented here delineate a very rare form of idiopathic benign generalized epilepsy presenting with typical absences before age of 3 years and a favorable outcome, similar to childhood and JAE, recognized as distinct IGE syndromes by the International League Against Epilepsy (ILAE) classification.

Differential stimulant response on attention in children with comorbid anxiety and oppositional defiant disorder.

Attention-deficit hyperactivity disorder (ADHD) affects 3% to 7% of school-age children. Approximately 30% of the children with ADHD also have comorbid anxiety or oppositional defiant disorder. Methylphenidate is the drug of choice for the medical treatment of such cases. When compared with children with ADHD alone, children with comorbid anxiety or oppositional defiant disorder may show worsening of the global attention score in response to methylphenidate and not only a "reduced response," as reported in previous studies. This study included 1122 children diagnosed as ADHD, of which 174 were diagnosed with comorbid anxiety and 141 with comorbid oppositional defiant disorder. All patients performed the Test of Variables of Attention before and after methylphenidate administration. A normal distribution (Gaussian distribution) of reaction to methylphenidate, as measured by the global ADHD score in children diagnosed as pure ADHD, was found. These findings were in contrast to children with ADHD and comorbid anxiety or oppositional defiant disorder who showed a bimodal distribution and hence represent a distinct population. In both groups with comorbid disorders, there was a larger subgroup in which significant worsening of global ADHD score occurred after methylphenidate administration (P < .05). Children with ADHD and comorbid anxiety or oppositional defiant disorder might represent clinically distinct populations in which inattention is secondary to those disorders; therefore, methylphenidate may be an inappropriate treatment for such children.

Childhood epilepsy with occipital paroxysms: difficulties in distinct segregation into either the early-onset or late-onset epilepsy subtypes.

The Commission on Classification and Terminology of the International League Against Epilepsy Childhood rigidly segregated epilepsy with occipital paroxysms into 2 separate syndromes with different predominant seizure types: early-onset seizure susceptibility type consisting of prolonged infrequent, nocturnal autonomic seizures and accompanied by eye deviation and ictal vomiting and late onset with short diurnal frequent seizures and visual ictal manifestations along with throbbing headaches. Epileptic clinical manifestations and electroencephalographic data were analyzed in 28 patients with suspected occipital lobe epilepsy in an attempt to segregate them into either the early or late forms according to the International League Against Epilepsy classification. Electroencephalography in 25 children demonstrated occipital epileptiform paroxysms compatible with the suspected epileptic syndrome. Only 14 (50%) children complied with the rigid criteria of either early-onset or late-onset presentations. The other 14 (50%) children presented with mixed diverse epileptic phenomena such as short-lived seizures in infancy or prolonged seizures during childhood, not complying with either rigid syndrome (ie, short-lived epileptic blindness at an early age or vomiting during later childhood). Despite present attempts to rigidly segregate childhood epilepsy with occipital paroxysms into 2 distinct epileptic syndromes, a high percentage of children still present with various mixed clinical phenomena. Therefore, clinicians should be aware of possible unique and unusual presentations of occipital lobe epilepsy at various ages.

A novel mutation of the CLN8 gene: is there a Mediterranean phenotype?

We report the first known case in Israel of a patient with an early childhood onset of ceroid-lipofuscinosis who is homozygous to a mutation of the CLN8 gene. This patient further expands the clinical varieties of CLN8, initially reported in Finland and Turkey and recently in Italy. The ultrastructural pathology of a skin biopsy specimen revealed abundant typical fingerprint profiles, but rare granular osmiophilic bodies and curvilinear structures. Sequencing of exon 3 of the CLN8 gene revealed a novel C>G missense mutation at a conserved amino acid glutamine 256 to glutamic acid. Our findings further raise the possibility of the existence of a Mediterranean CLN8 variant.

Childhood-onset idiopathic intracranial hypertension: relation of sex and obesity.

The purpose of the present study was to perform a meta-analysis of all children with idiopathic intracranial hypertension reported since 1997 combined with our experience in order to investigate sex distribution and frequency of obesity among young children up 11 years of age vs adolescents at age 12-17 years. Overall, 244 children diagnosed with idiopathic intracranial hypertension were found suitable for the proposed meta-analysis: 132 (54%) were younger than 11 years of age; 72 (55%) were male and 60 (44%) were female. In contrast, of 112 older children (age 12-17 years), 79 (70%) were female. The association between age and obesity could be analyzed in 147 patients: only 19 (26%) out of 74 younger children up to age 11 years were reportedly obese, whereas 47 (64%) out of 73 older children were found obese. Differences in age at presentation, sex, and obesity were statistically significant (P < 0.01). Thus, a wide-scale meta-analysis of childhood-onset idiopathic intracranial hypertension revealed that the female/male ratio in children younger than age 11 years seems to be fairly equal, with a relatively low rate of obesity, contrasting to a majority of females in the group of adolescents at high risk to become obese.

The Role of Prematurity in Patients With Hemiplegic Cerebral Palsy.

A multicenter retrospective study was conducted to investigate the perinatal factors, imaging findings and clinical characteristics of hemiplegic cerebral palsy with a particular focus on children born prematurely. Our cohort included 135 patients of whom 42% were born prematurely; 16% were extreme premature infants who were born at 30 weeks or earlier. Nineteen (14%) were twins. Right hemiplegia was slightly more common and accounted for 59% of the patients. Imaging findings of intraventricular hemorrhage and periventricular leukomalacia were more prevalent in premature children whereas stroke, porencephaly, cerebral hemorrhage and cerebral atrophy were more evenly distributed in both term-born and prematurely-born children (p< 0.01). The overall prevalence of epilepsy in the cohort was 26% with no differences in full-term compared to prematurely-born children. Regardless of the gestational birth age, intellectual deficits were more common in the presence of comorbidity of both hemiplegia and epilepsy (p< 0.05).

The clinical profile of children with ADHD that require OROS-methylphenidate combined with shorter-acting formulations.

Long-acting methylphenidate (MPH) formulations, including OROS-MPH, were found to be effective in alleviating ADHD symptoms throughout the day. However, sustained stimulant activity may lead to prolonged suppression of appetite and insomnia. In this study, we characterized the clinical profile of children and adolescents for whom a once-daily lower dose of OROS-MPH combined with a shorter-acting agent was more tolerable than single higher OROS-MPH dose. In our cohort of 128 children treated with OROS-MPH, 47 (36.7 %) better tolerated a lower dose of OROS-MPH combined with short-acting MPH formulations (Group I). Nevertheless, for the majority (81 patients-63.3 %), a standard single moderate dose of OROS-MPH was sufficient (Group II). The mean daily doses of MPH were: 0.83 ± 0.21 mg/kg for Group I and 1.06 ± 0.29 mg/kg for Group II. There were no significant differences in the prevalence of learning disorders, tic disorders, epilepsy and conduct disorders between these two groups. However, anxiety and marginally depression were more prevalent in Group I (46.8 and 9.7 %) than in Group II (27.2 and 1.2 %). Patients in Group I were also more tending to receive psychotherapy than patients in Group II.

The neurologic profile of children and adolescents with inflammatory bowel disease.

In recent years, there has been an increasing incidence of inflammatory bowel disease in children and adolescents. Neurologic involvement has been mainly reported in adults, and information in pediatrics is based primarily on individual case reports. In this study, we explored the prevalence and spectrum of neurologic manifestations of 50 children with inflammatory bowel disease in comparison to healthy controls. Based on clinical reports and neurologic evaluation, 34 patients (68%) exhibited neurologic manifestations compared with 10 children (23.8%) in the control group (P < .001). The main symptoms associated with inflammatory bowel disease in comparison to the control subjects were headache: 46% vs 3% (P < 0.001), dizziness: 26% vs none (P < .001), hypotonia: 10% vs none (P = .06), attention-deficit hyperactivity disorder (ADHD): 28% vs 7.1% (P < .001), tics and sensory complaints: 16% vs 2.4% (P = .036). Seizures and neuropsychiatric disorders were less characteristic. A larger-scale prospective study is required to further clarify this association.

Clinical characteristics of autism spectrum disorder in Israel: impact of ethnic and social diversities.

Despite the increased global prevalence and recognition of autistic spectrum disorder (ASD), it is still scarcely reported in the Arab world. Though Israel has a higher prevalence of ASD, a previous national survey of patients diagnosed between 1972 and 2004, demonstrated that 98% of them were of Jewish ancestry. The disproportional low number of Arab children with ASD in Israel is unclear but may reflect lower awareness and cultural bias. In the present study we collected clinical and demographic characteristics of 200 children with ASD from Arab and Jewish sectors in Israel that were evaluated in two child development centers. We compared the incidence and the medical comorbidity of autism between these two ethnics groups. The medical and psychiatric comorbidity profile in these children was similar to the worldwide published studies. In the present study the prevalence of autism in the Arab sector in Israel was similar to that of the Jewish sector. The Arab patients presented with more severe autistic manifestations and higher incidence of mental retardation, familial members with autism, and consanguinity (P < 0.05), while in the Jewish sector milder forms (such as Asperger syndrome and PDD-NOS) were more frequent. This discrepancy might be explained by both genetic and cultural factors.