Find out about the cases of Lucas, Martina and Sofía and how, thanks to genetic tests, they reached a diagnosis and treatment.

Today, genetics plays a crucial role in our understanding of neurodevelopmental pathologies, such as autism spectrum disorders (ASD).. At Enevia Health, we offer a variety of genetic tests, such as clinical exome, whole exome, and trio exome, which can provide valuable information for the diagnosis and treatment of these conditions. 

In this article, we will explore the importance of these tests, providing specific technical data and real case examples, and how they can improve the quality of life of those affected by neurodevelopmental disorders.

clinical exome

The clinical exome is a genetic test that analyzes approximately 7,000 genes, that is, the exons of genes, which are the parts of DNA that code for proteins. Although they only represent approximately 1-2% of the human genome, the exons contain the majority of mutations associated with genetic diseases. 

Clinical exome sequencing can identify genetic alterations associated with autism spectrum disorders and other neurodevelopmental pathologies, which allows a more accurate and early diagnosis.

whole exome

The whole exome is a test that analyzes approximately 20,000 genes, it is more exhaustive than the clinical exome, since it analyzes all exons of the human genome, including non-coding genes and intronic regions. This may provide a more complete picture of the genetic variants that may be involved in neurodevelopmental disorders. By identifying mutations in lesser-known or lesser-investigated genes, the whole exome can offer additional information to guide the diagnosis and treatment of these conditions.

For example, while the clinical exome can detect variants in genes known to be associated with ASD, the whole exome could identify variants in recently discovered or less studied genes that may also contribute to the onset of the disorder.

exome trio

The exome threesome is a genetic test that analyzes the exons of three people: the patient and his two biological parents. This test it is especially useful for identifying de novo mutations, which are genetic mutations that occur for the first time in an individual and are not present in their parents. De novo mutations are common in autism spectrum disorders and other neurodevelopmental pathologies. The exome trio helps clarify the genetic cause of these disorders and guide clinical decision-making.

The main difference between a targeted clinical exome and a whole exome consists in the number of genes analysed.

In a targeted clinical exome -also known as a "panel"- only the exons of a set of known genes that could be related to the pathology present in the patient are analysed. In contrast, in a complete exome, all the exons of currently known genes are sequenced, not only those related to known diseases, but also those with unknown or less studied functions.

In terms of coverage, a targeted clinical exome typically has 80-90% coverage, while the whole exome has 95% coverage or more. Because of this, the whole exome can provide additional information and may be more useful in cases of patients with diseases where the exact cause is unknown or if a panel for the pathology is not available. However, whole exome is more expensive and requires more processing and analysis time than clinical exome targeted.

In case of Lucas, a 4-year-old boy, presented delayed motor development and learning difficulties. Despite having been evaluated by various specialists and having performed various tests, a clear diagnosis had not been established for his situation. Her parents decided to resort to genetic testing at Enevia Health, in this case, a whole exome, in the hope of finding an answer that could guide Lucas's treatment.

Whole-exome results revealed a mutation in the SLC2A1 gene. This gene is responsible for the production of GLUT1, a protein that facilitates the transport of glucose through the blood-brain barrier to nourish the brain. The SLC2A1 mutation was associated with a rare disorder called GLUT1 deficiency syndrome, which causes insufficient glucose in the brain, affecting brain function and development.

By identifying the genetic mutation in SLC2A1, Lucas's medical team was able to establish an accurate diagnosis. GLUT1 deficiency syndrome and develop a specific treatment plan. This plan included the implementation of a ketogenic diet, which is high in fat and low in carbohydrates, designed to provide the brain with an alternative source of energy in the form of ketone bodies. This diet has been shown to be effective in treating some patients with GLUT1 deficiency syndrome, significantly improving their symptoms and quality of life.

In addition, treatment included physical and occupational therapy to address Lucas' learning and motor difficulties, as well as regular medical follow-up to assess and adjust treatment as needed.

The identification of the genetic mutation in SLC2A1 allowed Lucas's family to understand the cause of his symptoms and receive the appropriate treatment, which led to notable improvements in their development and general well-being. 

In case of Martina, a 2-year-old girl, showed delayed psychomotor development and episodes of intermittent muscle weakness. Despite having been evaluated by several specialists, no clear diagnosis had been reached that could explain her symptoms. Concerned about their daughter's well-being and the lack of progress in her development, her parents decided to perform a genetic test for exoma trio at Enevia Health to obtain more information that could guide Martina's treatment.

The results of the trio exome test revealed a de novo mutation in the CACNA1A gene, which was not present in either parent. This gene is responsible for encoding a subunit of a neuronal calcium channel, which plays an important role in the function and communication of neurons.

The CACNA1A mutation was associated with a disorder called familial ataxic episode syndrome type 2 (FAE2), which causes recurrent episodes of ataxia, muscle weakness, and impaired cognitive development.

The results of the trio exome test revealed a de novo mutation in the CACNA1A gene, which was not present in either parent. This gene is responsible for encoding a subunit of a neuronal calcium channel, which plays an important role in the function and communication of neurons. The CACNA1A mutation was associated with a disorder called familial ataxic episode syndrome type 2 (FAE2), which causes recurrent episodes of ataxia, muscle weakness, and impaired cognitive development.

By identifying the genetic mutation in CACNA1A, Martina's medical team was able to establish an accurate diagnosis of AD2 syndrome and design a specific treatment plan. Treatment included the use of acetazolamide, a medication that has proven effective in reducing the frequency and severity of ataxic episodes in patients with AD2. In addition, rehabilitation and support therapies were implemented to address the difficulties in Martina's psychomotor and cognitive development.

If the CACNA1A mutation had not been identified, Martina's prognosis could have been much worse, since the lack of adequate treatment would have allowed ataxic episodes and developmental difficulties to continue unchecked. By receiving early and appropriate treatment, Martina experienced significant improvements in her development and quality of life.

In case of Sofía, a 5-year-old girl, showed a delay in language development and difficulties in social interactions. Despite having visited various specialists, no precise diagnosis had been reached to explain his symptoms. His parents decided to undergo a trio exome genetic test offered by Enevia Health, in the hope of obtaining more information that could guide Sofia's treatment.

The results of the trio exome test revealed a de novo mutation in the SHANK3 gene, which was not present in either parent. This gene is involved in the development and function of neuronal synapses, and SHANK3 mutations have been associated with Phelan-McDermid syndrome, a neurodevelopmental disorder that includes symptoms similar to those on the autism spectrum.

With this information, Sofia's medical team was able to make an accurate diagnosis of Phelan-McDermid syndrome and design a personalized treatment plan. The plan included speech therapy, occupational therapy, and specialized educational support to address his difficulties with communication and social skills. In addition, the doctors were able to provide the family with information about support groups and resources specific to Phelan-McDermid syndrome.

Thanks to the identification of the genetic mutation in SHANK3, Sofia's family was able to understand the cause of her symptoms and receive the appropriate support to improve her quality of life. This case illustrates the importance of genetic tests, such as the exome trio, in the diagnosis and treatment of autism spectrum disorders and other neurodevelopmental pathologies.