Genetic causes of epilepsy

• characteristic facial features: increased distance between the eye slits, enlarged beak-shaped nose, the face often looks like a Greek helmet;
• ear deformity;
• malformations of internal organs (heart, genitourinary system);
• abnormalities of the musculoskeletal system.

The syndrome Martin—Bell (brittle X chromosome syndrome), develops due to a disorder in the gene FMR1, which is located on the X chromosome and plays an important role in the appearance and development of neural connections, learning and memorization. These changes are the most common known causes of inherited intellectual disability.  The syndrome includes symptoms such as:

• a large head with a high and wide forehead;
• long face with enlarged chin;
• slightly flattened middle part of the face;
• ears are large, protruding, low-set;
• the hands and feet are wide;
• joints have increased mobility;
• testicular enlargement.

Epilepsy in hereditary metabolic diseases

This group of diseases is the most interesting, because these pathologies can occur under the "masks" of other diseases.: epilepsy, perinatal pathology, cerebral palsy, neuroinfection. However, a number of them are amenable to pathogenetic therapy, and timely diagnosis can dramatically change the prognosis and treatment tactics.

What are the characteristics of hereditary diseases from the group of metabolic disorders?

• in most cases, they make their debut in infancy and early childhood;
• are accompanied by damage to the central nervous system;
• in the absence of therapy, diseases progress rapidly;
• if substitution therapy is possible, it is a positive response.

When is there a reason to turn to a geneticist?

• closely related marriage;
• a history of infant mortality, a history of neurological diseases;
• positive family history;
• excessive fetal movements during pregnancy (intrauterine seizures);
• unusual urine and body odors;
• severe metabolic acidosis;
• the presence of other neurological features: gait disorder, ataxia, spasticity;
• damage to more than one system: hepatosplenomegaly, retinitis pigmentosa;
seizures that occur or go away during fasting or are associated with a high-protein diet.

The following are examples of diseases from the group of hereditary metabolic disorders for which pathogenetic therapy has been developed.

The first of them is biotinidase deficiency, in which, due to a mutation in the BTD gene, the synthesis of the biotinidase enzyme is disrupted, which leads to disruption of the work of many enzymes. As a result, there is no cleavage of substrates and toxic metabolites accumulate.

Clinical manifestations depend on the residual activity of the enzyme and are characterized, in addition to epileptic seizures, by the following symptoms:

• Seborrhea
• Atopic dermatitis
• Nesting and/or total alopecia
• Persistent conjunctivitis
• Delayed psychomotor development
• Ataxia

Treatment: the main method of pathogenetic therapy is taking vitamin biotin, which is also called vitamin B7 or H.

The cause of the disease is a defect in the SLC2A1 gene, which encodes the GLUT1 protein, a type 1 glucose transporter responsible for delivering glucose from the blood to the brain through the blood-brain barrier. Mutations in the SLC2A1 gene disrupt the function of the GLUT1 protein, as a result, the brain is deprived of its main source of energy, glucose, which leads to a progressive impairment of its functions and the appearance of appropriate clinical symptoms. The clinical manifestations of this disease include:

• Microcephaly
• Spasticity
• Ataxia
• Dysarthria
• Alternating hemiplegia

Seizures are triggered by physical exertion, hunger, or increased intervals between meals.

Treatment: ketogenic diet, high-fat, low-carb diet. At the same time, the synthesis of ketone bodies, water-soluble compounds capable of penetrating the blood-brain barrier through another transporter protein, begins from fats. As an alternative source of energy, they contribute to the restoration of metabolic processes, thereby preventing further brain damage.

Another disease often accompanied by epilepsy is Glutaric aciduria, type 1. It is caused by mutations in the gene encoding the enzyme glutaryl-CoA dehydrogenase (GCDH). Deficiency of this enzyme leads to the accumulation of glutaric and 3-OH-glutaric (3-hydroxyglutaric) acids in biological fluids and tissues, which have a neurotoxic effect mainly on the subcortical structures of the brain. Clinical symptoms worth paying attention to:

• Macrocephaly
• Prominent frontal protuberances
• Feeding disorders
• Loss of skills
• Hyperkinetic form of cerebral palsy
• Periodic ataxia

Treatment: diet therapy with the exception of high-protein foods rich in lysine and tryptophan, the use of specialized products based on mixtures of amino acids without pathogenetically significant amino acids, the appointment of L-carnitine, riboflavin.

In conclusion, I would like to say that epileptic seizures are common symptoms of hereditary pathology, but hereditary diseases are a rare cause of epilepsy, this should be taken into account, and this should not be forgotten!