Combined exome analysis and exome depth assessment achieve a high diagnostic yield in an epilepsy case series, revealing significant genomic heterogeneity and novel mechanisms.

OBJECTIVES: Genetics of epilepsy are highly heterogeneous and complex. Lesions detected involve genes encoding various types of channels, transcription factors, and other proteins implicated in numerous cellular processes, such as synaptogenesis. Consequently, a wide spectrum of clinical presentations and overlapping phenotypes hinders differential diagnosis and highlights the need for molecular investigations toward delineation of underlying mechanisms and final diagnosis. Characterization of defects may also contribute valuable data on genetic landscapes and networks implicated in epileptogenesis. METHODS: This study reports on genetic findings from exome sequencing (ES) data of 107 patients with variable types of seizures, with or without additional symptoms, in the context of neurodevelopmental disorders. RESULTS: Multidisciplinary evaluation of ES, including ancillary detection of copy number variants (CNVs) with the ExomeDepth tool, supported a definite diagnosis in 59.8% of the patients, reflecting one of the highest diagnostic yields in epilepsy. CONCLUSION: Emerging advances of next-generation technologies and 'in silico' analysis tools offer the possibility to simultaneously detect several types of variations. Wide assessment of variable findings, specifically those found to be novel and least expected, reflects the ever-evolving genetic landscape of seizure development, potentially beneficial for increased opportunities for trial recruitment and enrollment, and optimized, even personalized, medical management.

Growth Hormone Deficiency due to p.(Gln467Argfs*64) Mutation in the ARID1B Gene in a Girl with Coffin-Siris Syndrome.

Introduction: Coffin-Siris syndrome (CSS) (MIM #135900) is an extremely rare genetic multisystemic disorder characterized by aplasia or hypoplasia of the upper phalanx of the fifth finger, moderate to severe cognitive and/or developmental delay, and characteristic facial features (thick lashes, hypertrichosis of the trunk, sparse hair). Congenital anomalies of the brain, kidney, and heart have been described but are less consistent across patients. Case presentation: We report a case of a 12-year-5-month-old girl with the clinical features of CSS, severe scoliosis, and epilepsy. Growth hormone deficiency was diagnosed at the age of 9 years. Recombinant human growth hormone (rhGH) treatment was started that resulted in a significant improvement of the growth velocity up to 5.4 cm/year (>90-97th centile). Next-generation sequencing identified a mutation in the ARID1B gene. Discusion: Despite its phenotypic heterogeneity, key features of CSS have become clearer and along with molecular diagnosis, a further global approach to improve the care of these individuals is enabled. Appropriate therapies for this population are needed to optimize growth and intellectual potentials.

Α case of seronegative autoimmune encephalitis associated with human herpesvirus-7 (HHV-7).

In the last 10 years, an increased number of patients presenting with acute encephalitis is being observed, a finding that is attributed to autoimmune mechanisms. Despite the fact that autoantibodies usually target the neuronal cell surface or synaptic proteins in the central nervous system (CNS), in many cases these remain undetectable, constituting a future diagnostic and therapeutic challenge. Human herpesvirus-7 (HHV-7) is proven to be a neurotropic virus, causing various neurological complications mostly in the adult population. We present the case of a 10-year-old girl, with confirmed active HHV-7 infection of the CNS, who developed acute seronegative autoimmune encephalitis. To our best knowledge, there is no literature concerning pediatric cases of autoimmune encephalitis following HHV-7 infection.

Novel Hemizygous Missense Variant of Spermine Synthase (SMS) Gene Causes Snyder-Robinson Syndrome in a Four-Year-Old Boy.

Snyder-Robinson syndrome (SRS) is an extremely rare X-linked intellectual disability syndrome (MRXSSR; MIM #309583). The main clinical features of SRS include psychomotor delay, hypotonia, and asthenic-type body habitus - reduced body weight and bone abnormalities (osteoporosis, fractures, kyphoscoliosis). We report a case of SRS with a hemizygous missense variant in the SMS gene,c.334C>G (p.Pro112Ala), in a 4-year-old boy, who initially developed hypotonia, delayed motor skills, and subsequently epilepsy. This variant in SMS was found to be de novo. To the best of our knowledge, this novel SMS gene variant has never been previously reported in disease-related variation databases, such as ClinVar or HGMD.

The challenges that parents of children with epilepsy face: A qualitative study.

OBJECTIVE: This qualitative study explored the challenges that Greek parents/caregivers of children with controlled epilepsy (CwE) face regarding the disorder. METHODS: Interviews were conducted based on open-ended questions guided by a review of the literature. A total of 91 parents/caregivers were recruited by neurologists at the neurology clinics of two Athens public hospitals. A hermeneutic phenomenological approach was used to explore parent/caregiver experiences. The data were grouped and analyzed through a textual interpretation. RESULTS: Two key challenges were identified for parents of CwE: the disclosure of epilepsy and the absence of adequate information about coping with epilepsy. Parents in Greece were hesitant to reveal their child's epilepsy to school staff and their wider social milieu. Also, although satisfied with the patient-centered approach they experienced with their hospital doctor, parents/caregivers found that they needed more education about the existing sources of psychosocial and emotional support to cope with their child's epilepsy personally and as a family. Finally, the parents/caregivers who let their child know about the epilepsy and discussed the implications with the child found that parent-child communication improved. CONCLUSION: This study provides valuable insight into the impact of epilepsy on parents of CwE, which might help hospital and school staff support families with greater understanding, sensitivity, and skill. The findings suggest that Greek authorities should staff hospitals and schools with experts and more systematically advertise sources of information about epilepsy and ways to cope with it.

Teachers' knowledge about epilepsy in Greece: Information sources and attitudes towards children with epilepsy during school time.

AIM: The aim of this study was to explore the sources of information for the educators in Greek primary and secondary schools with regard to epilepsy, first aid to seizures, and pupils' health conditions. METHOD: A semistructured anonymous 52-item questionnaire was sent to 100 public primary and secondary Greek schools from all districts. Two thousand thirty-seven teachers were approached; 446 questionnaires returned. The data were analyzed with SPSS20. Also, 70 head teachers were phone-interviewed with an open-ended unstructured questionnaire. The derived data were analyzed using mixed methodology. RESULTS: Twenty-two percent of the addressed educational community responded to the questionnaire, mostly women (66.6%). More responses came from urban areas (71.5%). The main source for the teachers to obtain information about epilepsy was found to be personal experience (37.75%) and internet (34.93%). Only a small percentage was referred to courses (6.2%). Eighty point three percent of the educators knew what epilepsy is, and 88.1% had the right view about the nature of the illness. However, 92% of the educators replied that they have not had adequate first aid training. Although 80.3% of the teachers believed that the school personnel are aware of the pupils' medical history, 85.48% of the teachers considered that they are informed about the pupils' condition from the parents/carers, and only 5.53% believed that the information came from the family doctor. Ninety-five point seventy percent of the educators declared a wish for further information and training about epilepsy. CONCLUSION: Knowledge and attitudes of the educators towards epilepsy are improved compared with those reported in previous studies conducted in Greece. However, there are still areas of uncertainty which need improvement. The necessity for more information about epilepsy and pupils' medical history along with appropriate training about seizure incidents seems crucial for the Greek educational community. Educational campaigns about epilepsy could improve teachers' knowledge of epilepsy to develop a well-informed and tolerant community. Further research in the field is necessary to provide teachers with accurate information about the illness and the ways to cope with it.

Long-term follow up of complete bladder exstrophy repair. A case report.

OBJECTIVE: Bladder exstrophy is a congenital anomaly which is not always successfully managed by surgery. Major goals of surgical intervention in such cases are preservation of normal renal function, development of adequate bladder function and urinary continence and avoidance of future urinary tract infections. We present 5-year data on a patient who underwent complete repair of the bladder exstrophy. CASE REPORT: We describe a full term female infant who presented at birth with complete bladder exstrophy. Complete repair of the condition was performed 3 days after birth (Ransley technique). During hospitalization the patient had a positive urinary culture with Candida lusitaniae, enterococcus and septicemia with Klebsiella pneumoniae ESBL. The patient had no complications until the age of 20 months when she developed an episode of pyelonephritis and five further episodes of cystitis with E. coli. Radiographic testing showed small bladder capacity (23 ml at the age of 3 years), bilateral vesicoureteral reflux, a long stenotic urethra and no loss of renal function. Because of the recurrent urinary tract infections, dilatations of the stenotic urethra (Scheldinger technique) were successfully performed at the age of 3. Twenty-two months later the child had negative urinary cultures, a normal renal function and had also gained partial control of the bladder sphincters. CONCLUSIONS: Surgical repair of bladder exstrophy remains a challenging surgery for the pediatric urologist. Following surgical correction both early and long-term post-operative complications may be present. Longitudinal follow up is required by an experienced team of health care professionals.