Refining the phenotypic spectrum of CCDC88A-related PEHO-like syndrome.

Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO) and PEHO-like syndromes are very rare infantile disorders characterized by profound intellectual disability, hypotonia, convulsions, optic, and progressive brain atrophy. Many causative genes for PEHO and PEHO-like syndromes have been identified including CCDC88A. So far, only five patients from two unrelated families with biallelic CCDC88A variants have been reported in the literature. Herein, we describe a new family from Egypt with a lethal epileptic encephalopathy. Our patient was the youngest child born to a highly consanguineous couple and had a family history of five deceased sibs with the same condition. She presented with postnatal microcephaly, poor visual responsiveness, and epilepsy. Her brain MRI showed abnormal cortical gyration with failure of opercularization of the insula, hypogenesis of corpus callosum, colpocephaly, reduced white matter, hypoplastic vermis, and brain stem. Whole exome sequencing identified a new homozygous frameshift variant in CCDC88A gene (c.1795_1798delACAA, p.Thr599ValfsTer4). Our study presents the third reported family with this extremely rare disorder. We also reviewed all described cases to better refine the phenotypic spectrum associated with biallelic loss of function variants in the CCDC88A gene.

First LIPA Mutational Analysis in Egyptian Patients Reveals One Novel Variant: Wolman Disease.

Lysosomal acid lipase (LAL) is a necessary enzyme for the hydrolysis of both triglycerides (TGs) and cholesteryl esters (CEs) in the lysosome. Deficiency of this enzyme encoded by the lipase A (LIPA) gene leads to LAL deficiency (LAL-D). A severe disease subtype of LAL-D is known as Wolman disease (WD), present with diarrhea, hepatosplenomegaly, and adrenal calcification. Untreated patients do not survive more than a year. The aim of this study was to assess the clinical and molecular characterizations of WD patients in Egypt. A total of seven patients (from five unrelated Egyptian families) were screened by targeted next-generation sequencing (NGS), and the co-segregation of causative variants was analyzed using Sanger sequencing. Furthermore, multiple in silico analyses were performed to assess the pathogenicity of the candidate variants. Overall, we identified three diseases causing variants harbored in the LIPA gene. One of these variants is a novel missense variant (NM_000235.4: c.1122 T > G; p. His374Gln), which was classified as a likely pathogenic variant. All variants were predicted to be disease causing using in silico analyses. Our findings expand the spectrum of variants involved in WD which may help to investigate phenotype-genotype correlation and assist genetic counseling. To the best of our knowledge, this is the first clinico-genetic study carried out on Egyptian patients affected with WD.

Biallelic loss of EMC10 leads to mild to severe intellectual disability.

The endoplasmic reticulum membrane protein complex subunit 10 (EMC10) is a highly conserved protein responsible for the post-translational insertion of tail-anchored membrane proteins into the endoplasmic reticulum in a defined topology. Two biallelic variants in EMC10 have previously been associated with a neurodevelopmental disorder. Utilizing exome sequencing and international data sharing we have identified 10 affected individuals from six independent families with five new biallelic loss-of-function and one previously reported recurrent EMC10 variants. This report expands the molecular and clinical spectrum of EMC10 deficiency, provides a comprehensive dysmorphological assessment and highlights an overlap between the clinical features of EMC10-and EMC1-related disease.

Surgical nuances in corpus callosotomy as a palliative epilepsy surgery.

Background: Corpus callosotomy is a well-established palliative procedure in selected patients with drug resistant epilepsy (DRE). It has a beneficial role in ameliorating generalized seizures mainly drop attacks. Here, we present some technical tips for performing callosotomy depending on the anatomical basis, to minimize craniotomy size and guard against inadvertently entering the lateral ventricles. Methods: This study was a retrospective review of patients who received corpus callosotomy at our institute as a palliative epilepsy surgery. We present our experience and surgical tips with the extraventricular technique of corpus callosotomy with comparison of surgery-related complications and operative time between extraventricular and conventional techniques in selected patients with DRE. Results: Our study included 34 patients. First group of patients included 14 patients who received conventional approach, while the extraventricular approach was done in 20 patients. Extraventricular approach showed significantly lower wound complications rate of 10% compared to 78% in intraventricular approach (P < 0.001). Mean operative time was significantly lower in extraventricular versus conventional technique with 52 min versus 94 min, respectively (P < 0.001). Planned extent of corpus callosotomy resection was achieved in all our patients using both approaches. Conclusion: The cleft of the septum pellucidum offers a natural pursuit to section corpus callosum strictly midline and completely extraventricular in well selected patients of DRE candidate for callosotomy. Performing corpus callosotomy in extraventricular approach provided better patients outcomes regarding surgery and wound-related complications when compared to conventional approach.

Sensorineural hearing loss imprint on fine motor skills: A pediatric and adolescent innovative study.

BACKGROUND: Sensorineural hearing loss is the most common type of permanent hearing impairment and results in balance and motor deficits in children which may affect and/or delay all developmental indicators. OBJECTIVE: The purpose of this study was to investigate the consequences of sensorineural hearing loss regarding fine motor skills in children and adolescents. METHODS: Two hundred children with an age range between 7 to 18 years and diagnosed with sensorineural hearing loss were selected from the Public School for the Deaf and Hard of Hearing in El-Minia district, Minia governorate, Egypt. The outcome was assessed by the use of Bruininks-Oseretsky Test of Motor Proficiency Second Edition scale (BOT-2) to measure fine motor skills. RESULTS: There was a statistically significant difference between the scores of Fine Motor Precision and Fine Motor Integration subtests of each study subgroup and its counterpart subgroup in the control group (normative values according to the scale) which has the same age and gender characteristics where p value equals (0.0008 or less, 0.0009 or less) respectively, with a large effect size less than -0.83. CONCLUSION: The findings of this study suggest that children with sensorineural hearing loss have a defect in their fine motor skills when compared to normal children of the same gender and age groups according to Bruininks-Oseretsky scale.

Role of Serum Level of Neurometals; Copper, Zinc and Magnesium in Neonates with Hypoxic Ischemic Encephalopathy.

BACKGROUND: Perinatal HIE is associated with high morbidity and mortality rates worldwide, despite the improvements in perinatal care. The aim of this study was to evaluate the role Cu, Zn, and Mg+2 neurometals in the development of neonatal hypoxic ischemic encephalopathy. METHODS: This study included two groups: group 1 (study group): Thirty full term, and diagnosed as having hypoxic ischemic encephalopathy. Group 2 (control group): Thirty full term healthy neonates. All the neonates included in the study were subjected to full history taking and complete clinical and neuromuscular examinations. Laboratory investigations were done in both groups and included complete blood picture, renal functions test, ESR, serum zinc, copper, magnesium, sodium, potassium, and calcium levels. RESULTS: There were high serum zinc and copper levels in the patient group compared to the control group. However, there was low serum magnesium, calcium, and sodium levels in the patient group compared to the control group. There was a significant difference regarding Apgar score at 1 minute and 5 minutes between patient and control groups. The mean ESR values in patient group at the first hour and second hour were higher in the patient than the control group. CONCLUSIONS: Neonates with perinatal asphyxia have significantly higher levels of serum zinc and copper and lower serum magnesium, calcium, and potassium levels compared to healthy non asphyxiated neonates. Copper, zinc, and magnesium may play an important role in the development of neonatal hypoxic ischemic encephalopathy; however, further studies are needed to support our findings.