Two Novel Compound Heterozygous Mutations in the TRAPPC9 Gene Reveal a Connection of Non-syndromic Intellectual Disability and Autism Spectrum Disorder.

Introduction: Autism spectrum disorder (ASD) is characterized by deficits in communication, social interaction, and repetitive behavior. Up to 70% of ASD cases are linked with intellectual disability (ID). The major genetic causes for ASD and ID are largely unknown, however, a shared genetic etiology between ASD and ID must be assumed.

Methylphenidate in children with monogenic obesity due to LEPR or MC4R deficiency improves feeling of satiety and reduces BMI-SDS-A case series.

Background: The clinical phenotype of patients with monogenic obesity due to mutations in the leptin receptor (LEPR) or melanocortin 4 receptor (MC4R) gene is characterized by impaired satiety and hyperphagia, leading to extreme, sometimes life-threatening weight gain.

Subjects/methods: In a case series, we analysed the effect of an off-label methylphenidate (MPH) use for 1 year as an individual treatment approach on eating behaviour (Child Eating Behaviour Questionnaire [CEBQ]), appetite (visual analogue scales) and body mass index (BMI) trajectories in five patients with severe obesity due to mutations in the LEPR (n = 3) or MC4R (n = 2) gene.

Results: After 1 year use of MPH (20 mg/day divided in two to three doses), BMI (Δ BMI : -0.

[Risk Factors for Mental Health Problems in Children with Cerebral Palsy and Spina Bifida].

Background: Children with cerebral palsy (CP) and spina bifida (SB) are at an increased risk for mental health problems. Aim of this study was to correlate disease specific and psychosocial risk factors with characteristic mental health problems.

Patients: 271 children with CP and 84 with SB aged 3-17 years were included in a cross sectional study of 15 centers.

Predictive Value of Thompson-Score for Long-Term Neurological and Cognitive Outcome in Term Newborns with Perinatal Asphyxia and Hypoxic-Ischemic Encephalopathy Undergoing Controlled Hypothermia Treatment.

Background: The so-called Thompson-score (TS) for newborns with hypoxic-ischemic encephalopathy (HIE) was developed before the introduction of controlled hypothermia as clinical routine. Information on the predictive value of TS in newborns undergoing therapeutic hypothermia to estimate long-term outcome is limited.

Objectives: To determine the predictive value of TS to estimate long-term cognitive and neurological outcome in newborns with perinatal asphyxia treated with controlled hypothermia.

Effects of Levetiracetam and Sulthiame on EEG in benign epilepsy with centrotemporal spikes: A randomized controlled trial.

Purpose: BECTS (benign childhood epilepsy with centrotemporal spikes) is associated with characteristic EEG findings. This study examines the influence of anti-convulsive treatment on the EEG.

Methods: In a randomized controlled trial including 43 children with BECTS, EEGs were performed prior to treatment with either Sulthiame or Levetiracetam as well as three times under treatment.

[Preschool Examination in Baden-Wuerttemberg: Results of a Survey by Local Health Authorities].

Aims: German federal states conduct preschool examinations of children, to assess risks to their success in school. In 2009, step 1 of the preschool examination (ESU) in the German federal state Baden-Wuerttemberg (BaW) was preponed to the second-to-last year of kindergarten (age 4-5) to gain enough time for developmental interventions. Procedures and practice of ESU by local health authorities (HAs) in step 1 and step 2 (last year of kindergarten) were analyzed to infer strengths, weaknesses and requirements for change in the current ESU format.

Mutations of PTPN23 in developmental and epileptic encephalopathy.

Developmental and epileptic encephalopathies (DEE) are a heterogeneous group of neurodevelopmental disorders with poor prognosis. Recent discoveries have greatly expanded the repertoire of genes that are mutated in epileptic encephalopathies and DEE, often in a de novo fashion, but in many patients, the disease remains molecularly uncharacterized. Here, we describe a new form of DEE in patients with likely deleterious biallelic variants in PTPN23.

Neurodevelopmental outcomes of extremely low birthweight infants randomised to different PCO targets: the PHELBI follow-up study.

Background: Tolerating higher partial pressures of carbon dioxide (PCO) in mechanically ventilated extremely low birthweight infants to reduce ventilator-induced lung injury may have long-term neurodevelopmental side effects. This study analyses the results of neurodevelopmental follow-up of infants enrolled in a randomised multicentre trial.

Methods: Infants (n=359) between 400 and 1000 g birth weight and 23 0/7-28 6/7 weeks gestational age who required endotracheal intubation and mechanical ventilation within 24 hours of birth were randomly assigned to high PCO or to a control group with mildly elevated PCO targets.

Effect of supplementation with long-chain ω-3 polyunsaturated fatty acids on behavior and cognition in children with attention deficit/hyperactivity disorder (ADHD): a randomized placebo-controlled intervention trial.

Objective: To determine whether supplementation with the long-chain omega-3 polyunsaturated fatty acids eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) affects behavioral symptoms and cognitive impairments in children 6-12 years of age diagnosed with attention-deficit/hyperactivity disorder (ADHD).

Study Design: The randomized, double-blind placebo-controlled 16 weeks trial was conducted with 95 children diagnosed with ADHD according to DSM-IV criteria. Behavior was assessed by parents, teachers and investigators using standardized rating scales and questionnaires.

Long-term outcome at age 7-10 years after extreme prematurity - a prospective, two centre cohort study of children born before 25 completed weeks of gestation (1999-2003).

Objective: We aimed to determine the long-term neurodevelopmental outcome in extremely preterm infants of 22-23 completed weeks' gestation as compared to infants of 24 weeks with immediate postnatal life support born in two German tertiary perinatal centres between 1999 and 2003.

Methods: Children were assessed for cognitive and neurological outcomes at the age of 7-10 years. The test battery included a neurological examination, the Wechsler Intelligence Scale for children (WISC-IV) and the Frostigs Developmental Test of Visual Perception (DTVP-2).

Biallelic SZT2 mutations cause infantile encephalopathy with epilepsy and dysmorphic corpus callosum.

Epileptic encephalopathies are genetically heterogeneous severe disorders in which epileptic activity contributes to neurological deterioration. We studied two unrelated children presenting with a distinctive early-onset epileptic encephalopathy characterized by refractory epilepsy and absent developmental milestones, as well as thick and short corpus callosum and persistent cavum septum pellucidum on brain MRI. Using whole-exome sequencing, we identified biallelic mutations in seizure threshold 2 (SZT2) in both affected children.

A case of phace syndrome and acquired hypopituitarism?

Background: PHACE is a neurocutaneous syndrome associated with: Posterior fossa brain malformations, large "segmental" facial hemangiomas, arterial cerebrovascular-, cardiovascular-, and eye anomalies.

Case Vignette: We are reporting a girl with PHACE syndrome. The patient had a congenital right-sided facial hemangioma with plaque-morphology.

Dihydrofolate reductase deficiency due to a homozygous DHFR mutation causes megaloblastic anemia and cerebral folate deficiency leading to severe neurologic disease.

The importance of intracellular folate metabolism is illustrated by the severity of symptoms and complications caused by inborn disorders of folate metabolism or by folate deficiency. We examined three children of healthy, distantly related parents presenting with megaloblastic anemia and cerebral folate deficiency causing neurologic disease with atypical childhood absence epilepsy. Genome-wide homozygosity mapping revealed a candidate region on chromosome 5 including the dihydrofolate reductase (DHFR) locus.

Intrauterine, early neonatal, and postdischarge growth and neurodevelopmental outcome at 5.4 years in extremely preterm infants after intensive neonatal nutritional support.

Objective: Extremely preterm infants are at risk for poor growth and impaired neurodevelopment. The objective of this study was to determine whether intrauterine, early neonatal, or postdischarge growth is associated with neurocognitive and motor-developmental outcome in extremely preterm infants.

Methods: Surviving children who were born between July 1996 and June 1999 at <30 weeks' gestation and with a birth weight <1500 g were evaluated at the age of school entry by application of (1) a standardized neurologic evaluation, (2) the Kaufmann Assessment Battery for Children, and (3) the Gross Motor Function Classification Scale.

Orofacial findings in conjunction with infantile cerebral paralysis in adults of two different age groups--a cross-sectional study.

Objectives: The objective of this cross-sectional study was to assess differentiated malocclusion symptoms and dental findings such as caries prevalence in patients suffering from infantile cerebral paralysis (CP, ICP), as well as the amount of dental and orthodontic treatment.

Subjects And Methods: Sixty-two patients suffering from infantile cerebral paralysis (ICP) aged from 18 to 78 years were included in the study and assigned to one of two groups according to age. The analysis was carried out on study models that had been measured using a caliper gauge and an electronic model-measuring procedure.

Neurodevelopmental follow-up of very preterm infants after proactive treatment at a gestational age of > or = 23 weeks.

Objective: To determine the long-term neurodevelopmental outcome in extremely preterm infants after offering life support to all infants > or = 23 weeks gestation ("pro-active management").

Study Design: With parental consent, all infants born at 23 to 25 completed weeks gestation were treated proactively. Surviving infants born from July 1996 to June 1999 were assessed for standardized cognitive and neurological outcomes at 5 years corrected age.

Randomized trial of early versus late enteral iron supplementation in infants with a birth weight of less than 1301 grams: neurocognitive development at 5.3 years' corrected age.

Background: Iron deficiency in early childhood may impair neurodevelopment. In a masked, randomized, controlled trial of early versus late enteral iron supplementation in preterm infants with birth weights of <1301 g, early iron supplementation reduced the incidence of iron deficiency and the number of blood transfusions.

Objective: We sought to examine whether early enteral iron supplementation improves neurocognitive and motor development in these infants.

Patients with adenosine deaminase deficiency surviving after hematopoietic stem cell transplantation are at high risk of CNS complications.

Adenosine deaminase (ADA) deficiency is a systemic metabolic disease that causes an autosomal recessive variant of severe combined immunodeficiency (SCID) and less consistently other complications including neurologic abnormalities. Hematopoietic stem cell transplantation (HSCT) is able to correct the immunodeficiency, whereas control of nonimmunologic complications has not been extensively explored. We applied HSCT in 15 ADA-deficient patients consecutively treated at our institutions since 1982 and analyzed long-term outcome.

Transcultural pediatrics: compliance and outcome of phenylketonuria patients from families with an immigration background.

Living in a foreign country with a different lifestyle and a different orientation is a many-faceted challenge for immigrants. A considerable percentage (30-50%) of patients with metabolic disease come from immigrant families from Turkey and the Middle East. Phenylketonuria is one example of metabolic disease in which severe mental retardation can be entirely prevented by early detection via newborn screening and consistent dietary treatment.

Mutations in the gene encoding capillary morphogenesis protein 2 cause juvenile hyaline fibromatosis and infantile systemic hyalinosis.

Juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH) are autosomal recessive conditions characterized by multiple subcutaneous skin nodules, gingival hypertrophy, joint contractures, and hyaline deposition. We previously mapped the gene for JHF to chromosome 4q21. We now report the identification of 15 different mutations in the gene encoding capillary morphogenesis protein 2 (CMG2) in 17 families with JHF or ISH.