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Genetic Diseases in Neurology

Since the discovery of the structure of the human genome and the elucidation of genetic mechanisms of inheritance, clinical neurology has benefited from advances in genetics and neuroscience. Out of all human genetic diseases, a significant percentage affects the nervous and neuromuscular system. The main reason why the nervous system exhibits the largest number of genetic diseases of any other system in the human body seems to be related to the fact that the very large percentage of human DNA genes is involved in the process of developing the nervous system. The elucidation of the molecular genetic mechanisms underlying more and more diseases of the nervous system is drastically modifying classical neurological "pathology". New nosological entities are recognized and others are eliminated based on their genetic background. Today we know that mutations in hundreds of different genes can cause different types of neurogenetic diseases.

Overall, neurogenetic diseases are common, since for example more than 1,000,000 people in the US suffer from some form of neuromuscular disease, and about 40% of them are under the age of 18. In this way, the classification-categorization of classical neurological "nosology" is drastically modified. There are now many genetic tests available to the clinical neurologist and surely this number will increase in the future, so that the early and valid diagnosis of neurological genetic diseases, even the rarest ones, can be made.

Types of inheritance

Neurogenetic diseases are inherited by all possible modes of inheritance, i.e. they can be autosomal recessive (parents are healthy carriers), autosomal dominant, with one parent affected or by de novo mutation (suddenly created in the sufferer, with no family history), but and sex-linked, with affected boys only. At the same time, the same type or category of disease can be caused by mutations in many different genes, such as Charcot-Marie-Tooth (CMT) neuropathies, girdle muscular dystrophies (LGMDs), Emery-Dreifuss muscular dystrophy (EDMD) and so on. with the responsible gene, the mode of inheritance of the disease also changes.

Indicatively, these diseases include:

  • Syndromic and non-syndromic epilepsies (80% heritability, depending on the syndrome. For example: MELAS, MERRF, TSC),

  • Ataxias (the best known of which Friedreich's Ataxia and Hereditary Spinocerebellar Ataxias: SCA 1,2,3 etc.)

  • Motor Neurone Diseases: amyotrophic lateral sclerosis (ALS, HSP) (9.7 relative risk among first-degree relatives)

  • Congenital Polyneuropathies (such as Charcot Marie Tooth Disease, hereditary amyloid neuropathy)

  • Muscular Dystrophies: DMD (Duchenne), Facioscapulohumeral muscular dystrophy (FSHD), Sm and Sm-Like Muscular Atrophy (LSM), for example SMA 1, Kennedy Disease (bulbospinal muscular atrophy -BSMA)

  • Leukodystrophies (Autosomal Dominant Leukodystrophy)

  • Movement Disorders: Parkinson's disease (6 relative risk among family members for onset of the disease under 50 years of age), Restless Legs Syndrome (40-90% heredity), Paroxysmal Kinesogenic or Non-Kinegenic Dyskinesia (PKD, PNKD), Dopa Responsive Dystonia (DRD) )

  • Ion channel disorders (Hypokalaseic Periodic Paralysis, Normokalemic Periodic Paralysis)

  • Autism (70-90% heredity)

  • Narcolepsy

  • Dementia and Psychiatric Diseases (Alzheimer's Dementia with 60-80% heritability, CADASIL, CARASIL)

  • Multiple sclerosis (25-76% heritability, with responsible genes such as CBLB, HLA-DRB1, METTL1, etc.)

  • Cerebrovascular (responsible NINJ2 gene, in smokers).


As far as the effort to investigate the etiology and primary prevention of genetic diseases is concerned, applied research occupies an important position. The fields of vector detection, prenatal and pre-symptomatic diagnosis, are among the main objects of research focus. It is often necessary for Neurologists-Geneticists to collaborate closely with doctors of other specialties, sometimes to assist in the diagnosis and sometimes to give them the interpretation of specialized genetic tests. With the screening of pre-symptomatic individuals (asymptomatic individuals but with a high risk of having inherited the pathogenic gene) and the possibility of prenatal screening, the prevention of these diseases is largely achieved.

The importance of prevention

In case of a sick member in the family, the risk of recurrence of the disease is high. The majority of hereditary diseases are currently not amenable to etiological treatment and essentially the only way of treatment remains prevention. The most effective way of prevention is to provide genetic counseling to people who are at risk of having a child with a genetic disease. The detection of these individuals is done, especially in countries such as Greece where Genetic Register Systems are completely lacking, by the diagnosis-identification of patients suffering from a genetic disease, when they seek medical help.

In order to give reliable genetic advice, three basic conditions are required:

  1. the accurate and documented diagnosis of the index patient,

  2. the genealogical tree of the family (at least three generations) and

  3. the knowledge of the mode of hereditary transmission of the disease.

Genetic counseling is a long and complex process. The basic principle that governs it is that the geneticist interprets, explains, discusses and helps the interested parties to make the best decision for them, systematically avoiding directing them directly or indirectly towards a solution. The psychological state of those who seek genetic counseling is an extremely important problem and needs special handling by scientists.

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