Genetic and clinical variations of developmental epileptic encephalopathies.

OBJECTIVE: The concept of 'developmental and epileptic encephalopathy (DEE)' recognises that in infants presenting with severe early-onset epilepsy, neurodevelopmental comorbidity may be attributable to both the underlying cause and to adverse effects of uncontrolled epileptic activity. There is no direct genotype - phenotype correlation in DEEs. This study aimed to report the genetic and phenotypic differences in patients with DEE. METHODS: Genetic evaluations of the patients were performed due to epilepsy combined with developmental delay, epileptic encephalopathy, motor deficits, autistic features, or cognitive impairment. Patients were assessed for demographic characteristics, medical history, family history, psychomotor development, seizure control interventions, electroencephalogram (EEG) and magnetic resonance imaging (MRI) findings. RESULTS: This study included 20 children aged 0-16 years who were diagnosed as having DEE.The types of DEE detected in our study were DEE 2, 4, 6B, 7, 11, 26, 30, 33, 35, 42, 58, 62, and 67.Status epilepticus was recorded in only DEE7. The most common EEG abnormality was multifocal epileptic discharges (35%,) followed by burst-suppression patterns in patients with neonatal-onset seizures. Thirteen of the children were aged over 2 years, two (15%) were non-ambulatory and six (46%) were non-verbal. MRI scans were normal in 80% of the patients. Refractory epilepsy seen in 33% of cases.De-novo mutation, microcephaly and dysmorphic findings accompany resistant seizures and are associated with poor prognosis. DISCUSSION: For patients with movement disorders, developmental delay, autism, and ID with or without epilepsy in any period of their life, next-generation sequencing is the only diagnostic technique available, with genetic analysis often being the only diagnostic method.

Lathosterolosis: a rare cholesterol metabolism disorder with a wide range of clinical variability.

OBJECTIVES: Lathosterolosis is a rare autosomal recessive congenital disease that occurs due to homozygous or compound heterozygous mutations in the sterol C5-desaturase (SC5D) gene. We report a male patient with biallelic missense variant detected in the SC5D gene. CASE PRESENTATION: An eight-month-old male patient was referred to the department of paediatric neurology for status epilepticus. He had no remarkable dysmorphic features except micrognathia, ptotic ear and thin-stranded hair. Laboratory tests revealed an alanine aminotransferase level of 502 IU/L and an aspartate aminotransferase level of 279 IU/L; other biochemical test results were normal. The brain MRI revealed atrophic changes in both hemispheres. A decrease in the volume of brain stem and thin corpus callosum were noticeable. Whole exome sequencing was performed because of consanguineous marriage and sibling death in his medical history, and the encountered features were consistent with suspected neurometabolic disease in the cranial imaging and the presence of borderline psychomotor retardation. A biallelic missense variant, c.656T>C p.(Leu219Ser), was identified in the SC5D gene. CONCLUSIONS: Lathosterolosis is a rare cholesterol metabolism disorder and can be presented with a wide range of clinical features by newly reported cases. Lathosterolosis should be considered in cases with cataracts, delayed neuromotor developmental milestones and high levels of liver enzymes.

A New Variant of the IER3IP1 Gene: The First Case of Microcephaly, Epilepsy, and Diabetes Syndrome 1 from Turkey.

Microcephaly, Epilepsy, and Diabetes Syndrome 1 (MEDS1) is a rare autosomal recessive disorder and caused by defects in the IER3IP1 (Immediate Early Response 3 Interacting Protein 1) gene. Only 9 cases have been described in the literature. MEDS1 manifests as microcephaly with simplified gyral pattern in combination with severe infantile epileptic encephalopathy and early-onset permanent diabetes. A simplified gyral pattern has been described in all cases reported to the date. Diagnosis is made by demonstration of specific mutations in the IER3IP1 gene. In this study, we present an additional case of a patient with MEDS1 who is homozygous for the c.53C >T p.(Ala18Val) variant. The case, the first to be reported from Turkey, differs from other cases due to the absence of a typical simplified gyral pattern on early brain MRI, the late onset of diabetes, and the presence of a new genetic variant. The triad of microcephaly, generalized seizures and permanent neonatal diabetes should prompt screening for mutations in IER3IP1.

The association between vitamin B12, folate, homocysteine levels, and carotid intima-media thickness in children with obesity: a cross-sectional study.

OBJECTIVES: We aimed to evaluate the association between vitamin B12, folate, homocysteine levels, and carotid intima-media thickness (CIMT) among children with obesity in whom vitamin deficiencies are more frequent. METHODS: Herein, 100 children with obesity (58 girls) were included (age, 5-18 years). Height, weight, body mass index (BMI), waist circumference (WC), puberty stage, blood pressure, and biochemical values were collected from medical records; standard deviations (SDS) and percentiles were calculated. Obesity was defined as BMI SDS of >+2SDS. Vitamin B12 and folate levels of <300 pg/mL and <4.8 ng/mL, respectively, were considered deficient. A radiologist quantified measurements from the carotid artery. RESULTS: Mean patient age was 12.52 ± 3.63 years. The mean weight SDS, BMI SDS, and WC/height were +3.37 ± 0.93, +2.93 ± 0.55, and 0.65 ± 0.05, respectively. In pubertal cases, insulin (p<0.001), the homeostatic model assessment for insulin resistance (HOMA-IR) (p=0.001) and homocysteine (p=0.002) levels were higher; vitamin B12 (p<0.001) and folate (p<0.001) levels were lower than those in prepubertal ones. WC and HOMA-IR correlated with CIMT; however, homocysteine levels were not correlated with CIMT. CONCLUSIONS: In our study, pubertal cases had lower vitamin B12 and folate levels as well as higher homocysteine levels. Although no correlation was identified between homocysteine levels and CIMT, this condition may be related to our study group comprising children, who had a shorter duration of obesity than those in adults. As CIMT was higher in children/adolescents with increased WC, it is proposed that they need central obesity more frequently and carefully follow-up.

The relationship between breast milk intake and speech in children with cerebral palsy

Background/aim: Cerebral palsy (CP) is a nonprogressive neurodevelopmental disorder that cause damage to the developing brain (0­3 years) for various reasons. Children with CP commonly have speech disorders due to impairment in neuromuscular control of oro-motor coordination. We focused on the relationship between breast milk intake and speech functions in children with CP. Materials and methods: The gross motor function classification system (GMFCS) was used to categorize the gross motor function. The viking speech scale (VSS) was used to classify the speech in children with cerebral palsy. Children were subdivided into two groups as term and preterm based on gestational age. The duration of exclusive breast milk intake was defined as the period when the infant received breast milk alone. We used Spearman's correlation coefficient to evaluate the relationship between the duration of breast milk intake, GMFCS, and VSS. Results: The median level of viking speech scale was 2 in preterm-born children and 4 in term-born children. There was no correlation between age and VSS levels.We observed a statistically significant difference in terms of preterm- or term-born status among children with different VSS levels. There was a weak positive correlation between birth weight and VSS level, indicating better speech function in children with lower birth weight. There was a moderate negative correlation between the duration of exclusive breast milk intake, the total duration of breast milk intake, and the corrected age of weaning completion with VSS level. Conclusion: The duration of breast milk intake may reflect the oromotor function and predict speech performance in children with cerebral palsy. We wanted to emphasize that speech language therapy is as important as motor rehabilitation.

Long-Term Follow-Up of Patients with a Diagnosis of Posterior Reversible Encephalopathy Syndrome.

OBJECTIVE: The essential characteristics of posterior reversible encephalopathy syndrome (PRES) are the presence of acute onset neurologic symptoms, focal vasogenic edema at neuroimaging, and reversible clinical and/or radiologic findings. This study aimed to evaluate the clinical findings, causes, radiologic findings, and prognoses of patients with PRES. METHODS: Patients with PRES confirmed with clinical and radiologic findings by a pediatric neurologist were evaluated retrospectively. RESULTS: Seventeen patients with PRES were evaluated (mean age at onset, 10.23 ± 4.65 years; range, 2-17 years; girls, 29.4% [n = 5]). The mean length of follow-up was 6 ± 2.3 years (range, 3.4-10 years). Mortality due to primary disease occurred in 4 patients (23.5%) during follow-up. PRES was derived from renal diseases in 10 patients (58.8%), hematologic diseases in 6 patients (35.3%), and liver disease in one patient (5.9%). Hypertension was present in 16 patients (94.1%) at onset of PRES (>99th percentile). Seizure, the most frequent initial symptom, was observed in 82.4% (n = 14). Blurred vision and headache were the initial symptoms in 3 patients (17.6%). Sequelae were observed at magnetic resonance imaging (MRI) in 6 patients. Development of epilepsy was determined as a sequela in 4 patients (23.5%) and mental motor retardation in 2 patients (11.8%). CONCLUSION: Epilepsy is uncommon in patients who have recovered from PRES. The presence of gliosis on MRI and interictal epileptic discharges on electroencephalograms are major risk factors for the development of epilepsy. Antiepileptic treatment can be stopped in the early period in patients with normal MRI and electroencephalogram by eliminating the factors that trigger the seizures.

Glutaric Acidemia Type 1: A Case of Infantile Stroke.

BACKGROUND: Glutaric acidemia Type 1 (GA-1) is an autosomal recessively inherited metabolic disorder which is associated with GCDH gene mutations which alters the glutaryl-CoA dehydrogenase, an enzyme playing role in the catabolic pathways of the amino acids lysine, hydroxylysine, and tryptophan. Clinical findings are often encephalopathic crises, dystonia, and extrapyramidal symptoms. CASE REPORT: A 9-month-old male infant referred to our department with focal tonic-clonic seizures during rotavirus infection and acute infarcts in MRI. Clinical manifestation, MRI findings, and metabolic investigations directed thoughts towards GA-I. Molecular genetic testing revealed a homozygous c.572T>C (p.M191T) mutation in GCDH gene which confirmed the diagnosis. Application of protein restricted diet, carnitine and riboflavin supplementations prevented the progression of Magnetic Resonance Imaging (MRI) and clinical pathologic findings during the 1 year of follow-up period. CONCLUSION: This case is of great importance since it shows possibility of infantile stroke in GA-1, significance of early diagnosis and phenotypic variability of disease.