Susanne Thümmler

Myoclonus in fraternal twin toddlers: a French family with a novel mutation in the SGCE gene.

Myoclonus dystonia is a rare movement disorder caused by mutations in the SGCE gene on chromosome 7q21 (DYT11) encoding the epsilon-sarcoglycan. Myoclonus is present in almost all patients and affects most often neck, trunk and upper limbs. Dystonia is present in about half of the patients. The mode of inheritance is autosomal dominant with variable clinical expression and maternal imprinting. Onset is usually in childhood or adolescence. Alcohol might relieve symptoms. We present a 33 month old girl and her twin brother with disabling involuntary jerky movements during intentional tasks. Family history of this French family was positive for the paternal uncle, his two daughters and the paternal great grandfather. Sequencing of the SGCE gene revealed a novel nonsense mutation c.942C>A (p.Tyr314X) in exon 7, confirming the diagnosis of myoclonus dystonia. Treatment with valproic acid significantly reduced myoclonic episodes and ameliorated life quality.

Pharmacoresistant Severe Mental Health Disorders in Children and Adolescents: Functional Abnormalities of Cytochrome P450 2D6

Background Severe mental health disorders in children and adolescents represent a major public health problem. Despite adequate drug treatment, some patients develop pharmacoresistant disease. As a consequence, physicians are confronted with prescribing challenges, prolonged hospitalization and increased risk of adverse events, thus aggravating short-, medium-, and long-term prognosis. The majority of psychotropic treatments, particularly antipsychotics and antidepressants, are metabolized at hepatic level by cytochrome P450 (CYP), particularly by CYP3A4 and CYP2D6. Several CYP2D6 genetic polymorphisms are described to be associated with ultrarapid (UM) or poor drug metabolism (PM), inducing clinical resistance and/or adverse events, and might therefore be related to pharmacoresistant severe mental health disease. Case presentation A total of nine pharmacoresistant patients (four females, five males) aged 11–16 (mean 14.1) years have been genotyped for CYP2D6 between January, 2015 and April, 2016. Patients were diagnosed with schizophrenia (n = 5), autism spectrum disorders (n = 2), intellectual disability with challenging behavior (n = 2), oppositional defiant disorder (n = 1), and post-traumatic stress and borderline personality disorders (n = 1). They had a treatment history with on average 6.1 (3–9) psychotropic, 5 (3–7) antipsychotic, and 3.4 (2–5) CYP2D6-metabolized antipsychotic and antidepressant molecules. Five patients (56%) presented functional anomalies of the CYP2D6 gene: three patients were UM metabolizers with gene duplication and two patients were PM with *4/*41 and *3/*4 polymorphisms. Conclusion Functional anomalies of CYP2D6 concerned more than half of our pediatric inpatient sample with pharmacoresistant disease. However, our case reports are limited by the low sample size. Nevertheless, knowledge of individual metabolism and in particular CYP2D6 genotyping should be considered for clinical workup and therapy adjustment in resistant patients in child and adolescent psychiatry and might permit better treatment outcome, increased treatment adherence and diminished adverse events.

Surdosage en carbamazépine par interaction avec les psychotropes : à propos de deux cas

Drug interaction is a frequent situation in pediatrics and child psychiatry. Carbamazepine (CBZ) is an antiepileptic drug used as a mood stabilizer in child psychiatry. CBZ is known to be a potent inducer of various CYP isoenzymes of cytochrome P450, which might result in a decrease in the plasma concentration of associated treatments. We describe two cases of CBZ overdosage in adolescent inpatients (14 and 16 years). The patients were treated with risperidone associated with fluoxetine in one and with loxapine in the other case, and CBZ was introduced as a mood stabilizer. Patients presented typical clinical symptoms (fatigue, dizziness, gastrointestinal signs, blurred vision). Overdosage was confirmed by an elevated CBZ plasma concentration (17 and 15.5 mg/L, therapeutic range 4-12 mg/L). We recommend introducing CBZ very progressively in patients treated with psychotropics, particularly when it is associated to several treatments. An intensification of clinical and biological follow-up with early plasma concentration testing should allow for better treatment adjustment.

Emergency organization of child psychiatric care following the terrorist attack on July 14, 2016, in Nice, France

In the actual context of terrorism targeting children and families, it seems essential to describe different experiences of pediatric psychological emergency devices after such unexpected mass trauma. Here we testify our experience of the psychological emergency care setup dedicated to children and families during the first 48 hours after the terrorist attack of Nice, France, on July 14, 2016. Activated within the hour following the attack, the device included two child psychiatry teams turning over each day, receiving at least 163 individuals (99 children and 64 adults) within the first 2 days. (Disaster Med Public Health Preparedness. 2019;13:144-146).

Exploration and characterisation of the phenotypic and genetic profiles of patients with early onset schizophrenia associated with autism spectrum disorder and their first-degree relatives: a French multicentre case series study protocol (GenAuDiss)

Introduction Early-onset schizophrenia (EOS) is a rare and severe condition. A higher rate of neurodevelopmental abnormalities, such as intellectual or communication impairments as well as attention deficit hyperactivity disorder, is observed in EOS compared with adult-onset schizophrenia. Early signs of autism spectrum disorders (ASD) are present in about 30% of patients. Genetic abnormalities, including copy number variations, are frequent in neurodevelopmental disorders and have been associated to ASD physiopathology. Implicated genes encode proteins involved in brain development, synapses morphology and plasticity and neurogenesis. In addition, an increasing number of genetic abnormalities are shared by EOS and ASD, underlying the neurodevelopmental hypothesis of EOS. The main objective of our study is to identify disease-causing genetic mutations in a cohort of patients affected by both EOS and ASD. Special attention will be paid to genes involved in neurodevelopmental pathways. Methods and analysis We describe a multicentric study in a paediatric population. The study started in April 2014. Inclusion criteria are: age 7–22 years, diagnosis of EOS with comorbid ASD and IQ >50; Parents and siblings are also enrolled. We perform psychiatric assessments (Mini International Neuropsychiatric Interview, Kiddie Schedule for Affective Disorders and Schizophrenia -Present and Lifetime Version, Positive and Negative Syndrome Scale and Scale for the Assessment of Negative Symptoms) together with neurocognitive evaluations (IQ, Trail Making Test A/B and verbal fluency). Then, we study variants of the coding part of DNA (exome), using next-generation sequencing process on trio (mother, father and child). Bioinformatics tools (RVIS and PolyPhen-2) are used to prioritise disease-causing mutations in candidate genes. The inclusion period will end in November 2019. Ethics and dissemination The study protocol was approved by the Local Ethic Committee and by the French National Agency for Medicines and Health Products Safety. All patients signed informed consent on enrolment in the study. Results of the present study should help to unravel the molecular pathology of EOS, paving the way for an early therapeutic intervention. Trial registration number NCT0256552; Pre-results.

Neurodevelopmental and immunological features in a child presenting 22q13.2 microdeletion.

Neurodevelopmental and Immunological Features in a Child Presenting 22q13.2 Microdeletion Susanne Th€ummler,* Fabienne Giuliano, Houda Karmous-Benailly, Christian Richelme, Arnaud Fernandez, Christine De Georges, and Florence Askenazy University Department of Child and Adolescent Psychiatry, Nice Children’s Hospitals CHU-Lenval, Nice, France Department of Human Genetics, University Hospital of Nice, Nice, France Department of Pediatrics, Nice Children’s Hospitals CHU-Lenval, Nice, France

PP05.9 – 2366: Neurodevelopmental and immunological features in a child presenting 22q13.2 microdeletion

Introduction Phelan-Mc Dermid syndrome (PMD) is a contiguous disorder resulting from the deletion of the distal arm of chromosome 22, generally implicating the SHANK3 gene on 22q13.3. Patients typically present neonatal hypotonia, developmental and speech delay, autistic features, normal or accelerated growth and minor morphological anomalies. In addition, several patients with 22q13 microdeletion proximal to SHANK3 and typical features of PMD are described. Case description We describe a 7-year old girl presenting a 0.54-Mb interstitial 22q13.2 microdeletion associated with neurological and immunological features. The patient presents different dysmorphic signs and macrocephaly. Neurological features include psychomotor and language retardation, coordination difficulties, repetitive behaviors and perseverations. In addition, the girl was affected by repetitive bronchiolitis since the age of 5 months, allergy to mites, treatment resistant asthma and vernal conjunctivitis. Discussion The chromosomal region deleted in our patient includes a dozen of genes including TNFRSF13C and NFAM1, two genes involved in B-cell development and related to autoimmunity. Therefore, this microdeletion probably explains not only neurodevelopmental anomalies evoking PMD but also immunological features including treatment-resistant vernal conjunctivitis, asthma and allergy. Recently, one other patient with a larger 22q13.2 microdeletion and similar clinical features has been described, thus helping for patients diagnostic work up. The case illustrates the importance to assess the full clinical picture. Genetic abnormalities might not only explain neurological features but also extra-neurological diseases, important for patients, their follow up and possible treatments.

Syphilis congénitale : à propos d’un cas

Resume La syphilis, dont l’incidence etait en diminution depuis les annees 1990, connait une recrudescence. La syphilis congenitale est une pathologie potentiellement grave qui affecte les nouveau-nes de meres infectees. C’est une maladie facilement curable par une simple antibiotherapie. Du fait d’un depistage systematique pendant la grossesse elle ne devrait plus exister dans les pays industrialises. Neanmoins nous rapportons le cas d’un nourrisson de six semaines avec un diagnostic retarde de syphilis congenitale.Syphilis is a re-emerging infectious disease in Western Europe. Congenital syphilis is a potentially serious pathology affecting newborns of infected mothers. This disease is easily curable by a simple antibiotic treatment. Because of systematic antenatal screening it should no longer exist in industrialized countries. Nevertheless, we report a case of a six-week-old infant with a delayed diagnosis of congenital syphilis. Physicians, especially gynaecologists, obstetricians and paediatricians, have to be vigilant in order to allow for early diagnosis and appropriate treatment of congenital syphilis.