Baris Korkmaz

Theory of Mind and Neurodevelopmental Disorders of Childhood

To a large extent, the human infant is socialized through the acquisition of a specific cognitive mechanism known as theory of mind (ToM), a term which is currently used to explain a related set of intellectual abilities that enable us to understand that others have beliefs, desires, plans, hopes, information, and intentions that may differ from our own. Various neurodevelopmental disorders, such as autism spectrum disorders, attention deficit hyperactivity disorder, developmental language disorders, and schizophrenia, as well as acquired disorders of the right brain (and traumatic brain injury) impair ToM. ToM is a composite function, which involves memory, joint attention, complex perceptual recognition (such as face and gaze processing), language, executive functions (such as tracking of intentions and goals and moral reasoning), emotion processing-recognition, empathy, and imitation. Hence, ToM development is dependent on the maturation of several brain systems and is shaped by parenting, social relations, training, and education; thus, it is an example of the dense interaction that occurs between brain development and (social) environment.

Benign rolandic epilepsy: neuropsychological findings

Benign rolandic epilepsy (BRE) is a partial idiopathic epilepsy of childhood presenting with a nocturnal seizure and with a typical EEG showing centrotemporal spike and multifocal or generalized sharp slow waves. Although normal neurological and intellectual development are expected in BRE, it is not infrequent to detect subtle defects in neuropsychological functions and neuromotor development. This study included 20 cases of BRE diagnosed according to the criteria of ILAE. The patients underwent several tests of neuropsychological functions as well as detailed neurological examination and the results were compared statistically to normal controls. In the patient group, a family history of language delay or learning disability (P < 0.005), presence of consanguinity (P < 0. 05), dyspraxia in the lower extremities (to imitation) (P < 0.05), difficulties in go-no-go test (P < 0.001), as well as some problems related to language such as dysprosody (P = 0.05), minor motor deficits in the left (P < 0.05) and right upper extremity (P < 0.05) were significantly more frequent compared to the control group. One should be rather guarded against the prognosis in BRE with respect to the higher cortical functions and neurodevelopmental problems.

Neuropsychological Functions in Idiopathic Occipital Lobe Epilepsy

Summary: Purpose: Despite the benign prognoses of idiopathic partial epilepsies, particularly regarding the response of seizures to treatment, some evidence now exists that patients with such disorders may have subtle neuropsychological deficits. This study was designed to investigate several modalities of neuropsychological functioning in a group of 21 patients, ranging from 6 to 14 years of age, with idiopathic occipital lobe epilepsy (IOLE). The case patients were compared with 21 healthy controls matched for age, sex, and socioeconomic status.

Functional deficiencies of sulfite oxidase: Differential diagnoses in neonates presenting with intractable seizures and cystic encephalomalacia

Sulfite oxidase is a mitochondrial enzyme encoded by the SUOX gene and essential for the detoxification of sulfite which results mainly from the catabolism of sulfur-containing amino acids. Decreased activity of this enzyme can either be due to mutations in the SUOX gene or secondary to defects in the synthesis of its cofactor, the molybdenum cofactor. Defects in the synthesis of the molybdenum cofactor are caused by mutations in one of the genes MOCS1, MOCS2, MOCS3 and GEPH and result in combined deficiencies of the enzymes sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase. Although present in many ethnic groups, isolated sulfite oxidase deficiency and molybdenum cofactor deficiency are rare inborn errors of metabolism, which makes awareness of key clinical and laboratory features of affected individuals crucial for early diagnosis. We report clinical, radiologic, biochemical and genetic data on a Brazilian and on a Turkish child with sulfite oxidase deficiency due to the isolated defect and impaired synthesis of the molybdenum cofactor, respectively. Both patients presented with early onset seizures and neurological deterioration. They showed no sulfite oxidase activity in fibroblasts and were homozygous for the mutations c.1136A>G in the SUOX gene and c.667insCGA in the MOCS1 gene, respectively. Widely available routine laboratory tests such as assessment of total homocysteine and uric acid are indicated in children with a clinical presentation resembling that of hypoxic ischemic encephalopathy and may help in obtaining a tentative diagnosis locally, which requires confirmation by specialized laboratories.

Novel VLDLR microdeletion identified in two Turkish siblings with pachygyria and pontocerebellar atrophy

Congenital ataxia with cerebellar hypoplasia is a heterogeneous group of disorders that presents with motor disability, hypotonia, incoordination, and impaired motor development. Among these, disequilibrium syndrome describes a constellation of findings including non-progressive cerebellar ataxia, mental retardation, and cerebellar hypoplasia following an autosomal recessive pattern of inheritance and can be caused by mutations in the Very Low Density Lipoprotein Receptor (VLDLR). Interestingly, while the majority of patients with VLDL-associated cerebellar hypoplasia in the literature use bipedal gait, the previously reported patients of Turkish decent have demonstrated similar neurological sequelae, but rely on quadrupedal gait. We present a consanguinous Turkish family with two siblings with cerebellar atrophy, predominantly frontal pachygyria and ataxic bipedal gait, who were found to have a novel homozygous deletion in the VLDLR gene identified by using high-density single nucleotide polymorphism microarrays for homozygosity mapping and identification of CNVs within these regions. Discovery of disease causing homozygous deletions in the present Turkish family capable of maintaining bipedal movement exemplifies the phenotypic heterogeneity of VLDLR-associated cerebellar hypoplasia and ataxia.

Novel NTRK1 mutations cause hereditary sensory and autonomic neuropathy type IV: demonstration of a founder mutation in the Turkish population

Hereditary sensory and autonomic neuropathy type IV (HSAN IV), or congenital insensitivity to pain with anhidrosis, is an autosomal recessive disorder characterized by insensitivity to noxious stimuli, anhidrosis from deinnervated sweat glands, and delayed mental and motor development. Mutations in the neurotrophic tyrosine kinase receptor type 1 (NTRK1), a receptor in the neurotrophin signaling pathway phosphorylated in response to nerve growth factor, are associated with this disorder. We identified six families from Northern Central Turkey with HSAN IV. We screened the NTRK1 gene for mutations in these families. Microsatellite and single nucleotide polymorphism (SNP) markers on the Affymetrix 250K chip platform were used to determine the haplotypes for three families harboring the same mutation. Screening for mutations in the NTRK1 gene demonstrated one novel frameshift mutation, two novel nonsense mutations, and three unrelated kindreds with the same splice-site mutation. Genotyping of the three families with the identical splice-site mutation revealed that they share the same haplotype. This report broadens the spectrum of mutations in NTRK1 that cause HSAN IV and demonstrates a founder mutation in the Turkish population.

Mucolipidosis type IV in a Turkish boy associated with a novel MCOLN1 mutation.

Mucolipidosis type IV is a rare neurodegenerative lysosomal storage disorder that usually presents during the first year of life with severe mental retardation, delayed motor milestones and corneal opacities. Mucolipidosis IV is caused by mutations in MCOLN1, a gene encoding mucolipin-1 which is responsible for maintaining lysosomal function. The majority of known patients with this disorders are Ashkenazi Jews, and most have a splice IVS3-2 A>G, or a 6.4kb deletion mutation in MCOLN1. Here, we present a Turkish patient who, in addition to the typical neurological and visceral characteristics of mucolipidosis type IV, also demonstrates defects in the posterior limb of internal capsule by MRI, micrognathia and clinodactyly of the fifth fingers. Direct sequencing of his DNA revealed a homozygous c.1364C>T (S456L) mutation in MCOLN1, which was heterozygous in both consanguineous parents. This mutation, like several previously described, changes the protein sequence in the channel pore domain of the protein. Serine 456 is conserved in mucolipin proteins throughout evolution, therefore the mutation is considered as causative for the severe phenotype of this patient.

Migration Abnormality in the Left Cingulate Gyrus Presenting With Autistic Disorder

Autism, characterized by an impairment in communication, including language, narrowly focused interests, and poor sociability, is a neurodevelopmental disorder of still largely unknown pathogenesis. In children with autistic symptomatology, the most consistent functional or anatomic abnormalities are found in the cingulate gyrus, particularly in the anterior regions. Neuronal migration malformations caused by incomplete neuronal migration and characterized by loss of the normal gyral patterns in the cerebral hemispheres and prominent disorganization of the cerebral cortical cytoarchitecture are generally associated with profound neurologic deficits, epilepsy, and autism. In this report, we present a case with an isolated migration abnormality located in the anterior part of the left cingulate gyrus who was admitted with the complaints of epileptic seizures and autism. In addition, the role of the localization of the migration abnormality in the appearance of autistic symptomatology is discussed. (J Child Neurol 2006;21:600—604; DOI 10.2310/7010.2006.00141).

A study on visual evoked responses in childhood epilepsy with occipital paroxysms

As some apparently idiopatic epilepsies may occasionally pose diagnostic difficulties in regard to their precise status of etiology, evoked potentials, particularly visual evoked potential (VEP), may contribute to the diagnosis of childhood epilepsy with occipital paroxysms (CEOP) as a subsidiary method of evaluation. This study includes 19 children (10 boys 52.6%; 9 girls 47.4%) ranging in age from 5 to 17 years (mean SD = 9.68 3.28) suffering from CEOP and a control group of 30 normal children, matched for chronological age and sex. Peak amplitudes and latencies of the P100 component for pattern-shift VEP (PVEP) and of major positivity for flash VEP (FVEP) are measured, respectively. The results from this study demonstrate that amplitude and latency values in patients with CEOP differs insignificantly when compared with controls. Although, non-significantly, mean values of amplitudes for both PVEP and FVEP were higher in the patients than in the normal children, whereas latencies in FVEP were somewhat longer. There may be some tendency for the amplitudes to increase and the latencies to be delayed in VEPs in patients with CEOP, when an overall interpretation of our and similar studies are considered. In certain cases of diagnostic difficulty, VEP values may provide further information for the clinician, regarding either a symptomatic or an idiopathic nature of the underlying disorder.

A patient with Duchenne muscular dystrophy and autism demonstrates a hemizygous deletion affecting Dystrophin

A Patient With Duchenne Muscular Dystrophy and Autism Demonstrates a Hemizygous Deletion Affecting Dystrophin Ozdem Erturk, Kaya Bilguvar, Baris Korkmaz, Yasar Bayri, Fatih Bayrakli, Zulfikar Arlier, Ali K. Ozturk, Cengiz Yalcinkaya, Beyhan Tuysuz, Matthew W. State, and Murat Gunel* Division of Child Neurology, Department of Neurology, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, Turkey Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut Program on Neurogenetics, Yale University School of Medicine, New Haven, Connecticut Division of Genetics, Department of Pediatrics, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, Turkey Department of Genetics, Yale University, New Haven, Connecticut Child Study Center, Yale University School of Medicine, New Haven, Connecticut Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut