scholarly journals Clinical and genetic characteristics of patients with type 2 early infantile epileptic encephalopathy caused by CDKL5 gene mutations

2020 ◽  
Vol 14 (3) ◽  
pp. 28-36
Author(s):  
E. L. Dadali ◽  
I. A. Akimova ◽  
F. A. Konovalov ◽  
P. A. Shatalov ◽  
A. Yu. Krasnenko ◽  
...  
Keyword(s):  
Genetic Variant ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Epileptic Seizures ◽  
Epileptic Encephalopathy ◽  
Psychomotor Retardation ◽  
Dominant Inheritance ◽  
Common Genetic Variant ◽  
Genetic Characteristics

Early infantile epileptic encephalopathies (EIEE) are a group of disorders characterized by pharmacoresistant epileptic seizures manifesting in infancy and leading to psychomotor retardation. The most common genetic variant with X-linked dominant inheritance is type 2 EIEE associated with CDKL5 gene mutations. We evaluated the prevalence of this type of EIEE among Russian patients (n = 148) with epileptic seizures manifesting in infancy and analyzed their clinical and genetic characteristics. We performed exome sequencing for all patients; 15 (10 %) of them (aged between 2 months and 5 years) were found to have CDKL5 gene mutations and were, therefore, diagnosed with type 2 EIEE. The results of correlation analysis suggest that the severity of clinical manifestations of type 2 EIEE is largely determined by the location of mutations affecting the function of the protein encoded by this gene. This is important to ensure better understanding of type 2 EIEE etiology and predict it severity in patients with different allelic variants.

scholarly journals Genetic epilepsy caused by CDKL5 gene mutations as an example of epileptic encephalopathy and developmental encephalopathy: literature review and own observations

2021 ◽  
Vol 16 (1-2) ◽  
pp. 10-41
Author(s):  
K. Yu. Mukhin ◽  
O. A. Pylaeva ◽  
M. Yu. Bobylova ◽  
V. A. Chadaev
Keyword(s):  
Literature Review ◽  
Genetic Disorders ◽  
Clinical Manifestations ◽  
Case Series ◽  
Gene Mutations ◽  
Epileptic Encephalopathy ◽  
Serine Threonine Kinase ◽  
Gene Encoding ◽  
Threonine Kinase

The disease caused by mutations in the CDKL5 gene (encoding cyclin-dependent kinase 5, CDK5) belongs to the group of early (infantile) epileptic encephalopathies caused by alterations in the genome. Currently, the disease is called “developmental encephalopathy and epileptic encephalopathy type 2”. This disorder is a complex combination of symptoms that develop due to deficiency or absence of the CDKL5 gene product, which is serine/threonine kinase. The CDKL5 gene is located on X chromosome; the disease has an X-linked dominant inheritance pattern. This literature review summarizes relevant studies analyzing the disease caused by CDKL5 gene mutations, including its genetic and epidemiological aspects, clinical manifestations, characteristics of epilepsy, principles of diagnosis, and therapeutic approaches. We present a case series of several patients with genetic disorders involving the CDKL5 gene.

scholarly journals PRRT2 gene variant in a child with dysmorphic features, congenital microcephaly, and severe epileptic seizures: genotype-phenotype correlation?

2019 ◽  
Vol 45 (1) ◽  
Author(s):  
Piero Pavone ◽  
Giovanni. Corsello ◽  
Sung Yoon Cho ◽  
Xena Giada Pappalardo ◽  
Martino Ruggieri ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Transmembrane Protein ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Epileptic Seizures ◽  
Epileptic Encephalopathy ◽  
Dysmorphic Features ◽  
Severe Intellectual Disability ◽  
Infantile Epilepsy ◽  
Congenital Microcephaly

Abstract Background Mutations in Proline-rich Transmembrane Protein 2 (PRRT2) have been primarily associated with individuals presenting with infantile epilepsy, including benign familial infantile epilepsy, benign infantile epilepsy, and benign myoclonus of early infancy, and/or with dyskinetic paroxysms such as paroxysmal kinesigenic dyskinesia, paroxysmal non-kinesigenic dyskinesia, and exercise-induced dyskinesia. However, the clinical manifestations of this disorder vary widely. PRRT2 encodes a protein expressed in the central nervous system that is mainly localized in the pre-synaptic neurons and is involved in the modulation of synaptic neurotransmitter release. The anomalous function of this gene has been proposed to cause dysregulation of neuronal excitability and cerebral disorders. Case presentation We hereby report on a young child followed-up for three years who presents with a spectrum of clinical manifestations such as congenital microcephaly, dysmorphic features, severe intellectual disability, and drug-resistant epileptic encephalopathy in association with a synonymous variant in PRRT2 gene (c.501C > T; p.Thr167Ile) of unknown clinical significance variant (VUS) revealed by diagnostic exome sequencing. Conclusion Several hypotheses have been advanced on the specific role that PRRT2 gene mutations play to cause the clinical features of affected patients. To our knowledge, the severe phenotype seen in this case has never been reported in association with any clinically actionable variant, as the missense substitution detected in PRRT2 gene. Intriguingly, the same mutation was reported in the healthy father: the action of modifying factors in the affected child may be hypothesized. The report of similar observations could extend the spectrum of clinical manifestations linked to this mutation.

scholarly journals On the study of seizures in newborns and early age children (features of diagnosis and clinical and genetic characteristics of epileptic encephalopathies)

2021 ◽  
pp. 37-50
Author(s):  
V.Yu. Martyniuk ◽  
◽  
T.K. Znamenska ◽  
V.B. Shveikina ◽  
V.A. Galagan ◽  
...  
Keyword(s):  
Young Children ◽  
Metabolic Disorders ◽  
Molecular Genetic ◽  
Nerve Impulse ◽  
Epileptic Seizures ◽  
Short Review ◽  
Epileptic Encephalopathy ◽  
Genetic Characteristics ◽  
Epileptic Encephalopathies ◽  
Metabolic Defects

The article is devoted to the urgent problem of neonatology and pediatric neurology — seizures in newborns and young children. In the work, a short review of the clinical and genetic characteristics of monogenic epilepsy is presented, in particular, the main attention is paid to the variants that begin in neonatal and early childhood. It has been shown that a significant number of epileptic encephalopathies are caused by mutations in genes whose protein products form voltage-dependent (sodium and potassium), ligan(dependent (γ-aminobutyric acid — GABA) channels, the functioning of which ensures the passage of a nerve impulse in neurons of the cerebral cortex. The necessity of including the molecular genetic methods into the algorithm for examining a child with epilepsy, in particular with epileptic encephalopathy, is emphasized. It is noted that congenital metabolic disorders are one of the etiological reasons for the development of epileptic seizures in children, in particular in newborns and young children. It was shown that congenital metabolic disorders have phenotypic manifestations of epileptic encephalopathy. Some curable metabolic defects that are accompanied by seizures, their diagnosis and timely treatment are described. No conflict of interest was declared by the authors. Key words: newborn, epilepsy, epileptic encephalopathy, diagnosis, genetic examination, metabolic defects, review.

Epileptic Encephalopathy, Myoclonus–Dystonia, and Premature Pubarche in Siblings with a Novel C-Terminal Truncating Mutation in ATRX Gene

2019 ◽  
Vol 50 (05) ◽  
pp. 327-331 ◽  
Author(s):  
Thea Giacomini ◽  
Maria Stella Vari ◽  
Sara Janis ◽  
Giulia Prato ◽  
Livia Pisciotta ◽  
...  
Keyword(s):  
Wide Spectrum ◽  
Genetic Disorder ◽  
Clinical Manifestations ◽  
Epileptic Seizures ◽  
Epileptic Encephalopathy ◽  
Recessive Mutations ◽  
Truncating Mutation ◽  
Alpha Thalassemia ◽  
Male Patients ◽  
Myoclonus Dystonia

AbstractThe X-linked alpha thalassemia mental retardation (ATR-X) syndrome is a genetic disorder caused by X-linked recessive mutations in ATRX gene, related to a wide spectrum of clinical manifestations, such as alpha thalassemia, developmental delay, genital abnormalities, and gastrointestinal disorders. Patients with ATR-X syndrome can suffer from different types of epileptic seizures, but a severe epileptic encephalopathy pattern has not been described to date. We describe, for the first time, two brothers with genetically confirmed ATR-X syndrome who presented with drug-resistant epileptic encephalopathy, with tonic and polimorphic seizures reported in the elder brother and epileptic spasms in the younger brother. Moreover, both brothers showed a peculiar movement disorder with myoclonus–dystonia, worsened during periods of distress or pain. These cases expand the clinical spectrum of ATR-X syndrome and open new opportunities for the molecular diagnosis of ATRX mutations in male patients with severe epileptic encephalopathies and movement disorders.

MTNR1B common genetic variant is associated with type 2 diabetes mellitus risk

Gene Reports ◽  
2020 ◽  
Vol 20 ◽  
pp. 100695
Author(s):  
Nina Saki ◽  
Negar Sarhangi ◽  
Mahdi Afshari ◽  
Fatemeh Bandarian ◽  
Hamid Reza Aghaei Meybodi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Genetic Variant ◽  
Common Genetic Variant ◽  
Diabetes Mellitus Risk

scholarly journals Homozygous SCN2A gene mutation causing early infantile epileptic encephalopathy: The second case in literature

2019 ◽  
Vol 6 (9) ◽  
pp. 221-223 ◽  
Author(s):  
Hale Önder Yılmaz
Keyword(s):  
Sanger Sequencing ◽  
Autosomal Dominant ◽  
Gene Mutations ◽  
Illumina Miseq ◽  
Epileptic Encephalopathy ◽  
Inherited Disease ◽  
Coding Regions ◽  
Analysis Platform ◽  
Neuronal Type

Objective: Early infantile epileptic encephalopathy type11 (EIEE) generally known as an autosomal dominant inherited disease caused by the voltage-gated sodium channel neuronal type 2 alpha subunit (Navα1.2) encoded by the SCN2A gene mutations. The clinic of the disease is variable. Herein we report the second case with a homozygous missense mutation of the SCN2A gene (c.1588 G>T). Material and methods: NGS gene panel including the SCN2A gene from genomic DNA extracted from peripheral blood using a commercially available kit and quantified using standard methods. Illumina miseq analysis platform was used for this purpose, we performed analysis of coding regions and exon-intron boundaries and the data was analyzed by IGV. Results: The results confirmed by sanger sequencing show us an SCN2A (NM_001040142) c.1588 G>T homozygote mutation. Conclusion: This shows us more clinical and molecular studies need for SCN2A associated disease pathogenesis

scholarly journals Analysis on the pathogenic genes of 60 Chinese children with congenital hyperinsulinemia

2018 ◽  
Vol 7 (12) ◽  
pp. 1251-1261
Author(s):  
Zi-Di Xu ◽  
Wei Zhang ◽  
Min Liu ◽  
Huan-Min Wang ◽  
Pei-Pei Hui ◽  
...  
Keyword(s):  
Clinical Manifestations ◽  
Gene Mutations ◽  
Chinese Children ◽  
Treatment Modalities ◽  
Partial Pancreatectomy ◽  
Genetic Characteristics ◽  
Pathogenic Genes ◽  
Second Generation Sequencing ◽  
Long Term Prognosis

This study aims to summarize and analyze the clinical manifestations, genetic characteristics, treatment modalities and long-term prognosis of congenital hyperinsulinemia (CHI) in Chinese children. Sixty children with CHI, who were treated at Beijing Children’s Hospital from January 2014 to August 2017, and their families, were selected as subjects. The CHI-related causative genes in children were sequenced and analyzed using second-generation sequencing technology. Furthermore, the genetic pathogenesis and clinical characteristics of Chinese children with CHI were explored. Among the 60 CHI children, 27 children (27/60, 45%) carried known CHI-related gene mutations: 16 children (26.7%) carried ABCC8 gene mutations, seven children (11.7%) carried GLUD1 gene mutations, one child carried GCK gene mutations, two children carried HNF4α gene mutations and one child carried HADH gene mutations. In these 60 patients, eight patients underwent 18F-L-DOPA PET scan for the pancreas, and five children were found to be focal type. The treatment of diazoxide was ineffective in these five patients, and hypoglycemia could be controlled after receiving partial pancreatectomy. In conclusion, ABCC8 gene mutation is the most common cause of CHI in Chinese children. The early genetic analysis of children’s families has an important guiding significance for treatment planning and prognosis assessment.

scholarly journals Clinical and genetic characteristics and orthopedic manifestations of the Saul–Wilson syndrome in two Russian patients

2021 ◽  
Vol 8 (4) ◽  
pp. 451-460
Author(s):  
Tatyana V. Markova ◽  
Vladimir M. Kenis ◽  
Evgenii V. Melchenko ◽  
Nina A. Demina ◽  
Polina Gundorova ◽  
...  
Keyword(s):  
Age Groups ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Protein Molecule ◽  
Published Data ◽  
Genetic Characteristics ◽  
Major Mutation ◽  
The Face ◽  
Modern Classification ◽  
Thin Bone

Background. SaulWilson syndrome (SWS, microcephalic osteodysplastic dysplasia) is a rare genetic variant of skeletal dysplasia and is determined based on the modern classification for thin bone dysplasias. To date, 16 patients with SWS from different countries have been identified. Clinical cases. We presented the first description of the clinical and genetic characteristics of two Russian patients with SWS and compared them with published data. The main clinical manifestations of SWS are characterized by a combination of nanism and pathology of long tubular bones, spine, and eyes. Changes in the phenotype of patients in different age groups were analyzed. Discussion. In the analysis of the clinical manifestations of the observed patients and patients described in the literature, typical dysmorphic features of the face and radiographic data help in the diagnosis of SWS upon clinical examination. In the majority of the described patients, the nucleotide substitution c.1546GA is the major mutation in the gene responsible for SWS, which leads to the replacement of the amino acid Gly516Arg in the protein molecule. Conclusion. Based on the identified specific features of the phenotype of patients with SWS and the presence of a major mutation in the COG4 gene, a priority analysis of gene mutations is necessary. Orthopedic manifestations of SWS can lead to life-threatening conditions (cervical spine instability) and motor limitations (progressive osteoarthritis) and thus should be monitored dynamically.

Sign in / Sign up

Export Citation Format

Share Document