No abstract

Purpose: DEPDC5 (DEP Domain-Containing Protein 5) encodes an inhibitory component of the mTOR pathway and is commonly implicated in sporadic and familial focal epilepsies, both non-lesional and in association with focal cortical dysplasia. Germline pathogenic variants are typically heterozygous and inactivating. We describe a novel phenotype caused by germline biallelic missense variants in DEPDC5. Methods: Cases were identified clinically. Available records, including MRI and EEG, were reviewed. Genetic testing was performed by whole exome and whole genome sequencing and cascade screening. In addition, immunohistochemistry was performed on skin biopsy. Results: The phenotype was identified in nine children, eight of which are described in detail herein. Six of the children were of Irish Traveller, two of Tunisian and one of Lebanese origin. The Irish Traveller children shared the same DEPDC5 germline homozygous missense variant (p.Thr337Arg), whereas the Lebanese and Tunisian children shared a different germline homozygous variant (p.Arg806Cys). Consistent phenotypic features included extensive bilateral polymicrogyria, congenital macrocephaly and early-onset refractory epilepsy, in keeping with other mTOR-opathies. Eye and cardiac involvement, and severe neutropenia, were also observed in one or more patients. Five of the children died in infancy or childhood, the other four are currently aged between five months and six years. Skin biopsy immunohistochemistry was supportive of hyperactivation of the mTOR pathway. Discussion: The clinical, histopathological and genetic evidence supports a causal role for the homozygous DEPDC5 variants, expanding our understanding of the biology of this gene.

IntroductionPseudoneurological symptoms are frequent among children consulting in neuropediatrics. Psychogenic origin is often unrecognized, which may cause a major disruption and an increase of medical care expenses.ObjectivesThe purpose of this study was to identify clinical features of pseudoneurological symptoms through patients admitted in neuropediatrics.MethodsA descriptive retrospective study of a population of 19 children and adolescents hospitalized in the neuropediatrics department at the National Institute of Neurology in Tunis, between January 2015 and April 2019, having recieved the diagnosis of psychogenic symptoms.ResultsTwelve girls and seven boys were included in this study.The averge age were 11.5 years. All patients had normal cogntive and motor development. In most cases (84%), patients had a history of somatic illness. Only three patients had a history of psychiatric disorders. Family history of somatic disorders was found in 42 % of the sample and psychiatric disorders in three patients. Negative pseudoneurological symptoms such as loss of function, were detected in 60 % of patients, paraparesis and paraplegia were the most recurrent. Only one patient had pseudo-epileptic symptoms. Further investigations were performed in all patients, averaging 4 tests per patient. The average term between the beginning of the symptoms and the established diagnosis of psychogenic symptoms was 72 days with an average stay at hospital of 4 to 7 days. All patients had conversion disorder according to DSM V.ConclusionsIt is recognized that somatization could be a warning sign of psychological distress mainly among children. Conversion disorder, rarely seen in children, presents frequently as pseudo neurological symptoms.