non-syndromic X-linked intellectual disability 77

Non-syndromic X-linked intellectual disability (NS-XLMR) refers to a condition characterized by intellectual disability in the absence of other symptoms or signs, whereas syndromic XLID patients display intellectual disability along with associated physical, neurological and/or psychiatric manifestations.

Causes and Characteristics:

• NS-XLMR is caused by mutations in genes located on the X-chromosome.
• The condition affects males more frequently than females, as they have only one X-chromosome.
• Females with one affected X chromosome and one normal X chromosome tend to have milder symptoms.
• Intellectual disability is the primary symptom of NS-XLMR, without any associated physical or neurological manifestations.

Prevalence and Inheritance:

• The prevalence of NS-XLMR is unknown.
• It is inherited in an X-linked recessive pattern, meaning that males are more likely to be affected than females.

Age of Onset:

• Intellectual disability associated with NS-XLMR typically becomes apparent in childhood or infancy.

References:

• [10] The X-chromosome has historically been the most thoroughly studied chromosome with regard to NS-ID due to the high male to female ratio. There are approximately 40 genes known to cause NS-ID, and ~80% of these reside on the X-chromosome.
• [11] X-linked intellectual disability refers to medical disorders associated with X-linked recessive inheritance that result in intellectual disability.. As with most X-linked disorders, males are more heavily affected than females. [1] Females with one affected X chromosome and one normal X chromosome tend to have milder symptoms.. Unlike many other types of intellectual disability, the genetics ...
• [12] Nonspecific X-linked intellectual deficiencies (MRX) belong to the family of sex-linked intellectual deficiencies (XLMR). In contrast to syndromic or specific X-linked intellectual deficiencies (MRXS), which also present with associated physical, neurological and/or psychiatric manifestations, intellectual deficiency is the only symptom of MRX.
• [14] Mondo Description Nonspecific X-linked intellectual deficiencies (MRX) belong to the family of sex-linked intellectual deficiencies (XLMR). In contrast to syndromic or specific X-linked intellectual deficiencies (MRXS), which also present with associated physical, neurological and/or psychiatric manifestations, intellectual deficiency is the only symptom of MRX.

Non-syndromic X-linked intellectual disability (NS-XLMR) presents with a range of signs and symptoms, primarily affecting males due to its X-linked recessive inheritance pattern. The clinical features of NS-XLMR can vary in severity and may include:

• Intellectual Disability: The primary symptom of NS-XLMR is intellectual disability, which can range from mild to severe.
• Weak Muscle Tone (Hypotonia): Many affected individuals exhibit weak muscle tone, leading to delayed motor skills such as sitting, standing, and walking [9].
• Facial Dysmorphism: Some individuals with NS-XLMR may display facial dysmorphism, which can include features such as a high palate, bifid uvula, or other minor anomalies [4].
• Neurological Signs and Symptoms: Affected individuals may experience neurological signs and symptoms, including strabismus (crossed eyes), seizures, and neuromuscular deficits.
• Behavioral Problems: NS-XLMR can also be associated with behavioral problems, such as autism, anxiety, or other psychiatric issues [5].
• Abnormalities of Various Organ Systems: In some cases, individuals with NS-XLMR may exhibit abnormalities in various organ systems, including the genitourinary system (e.g., enuresis) and the eye.

It's essential to note that not all individuals with NS-XLMR will display these symptoms, and the severity can vary widely among affected males. The diagnosis of NS-XLMR is often made through a combination of clinical evaluation, family history, and genetic testing [8].

References: [4] Kleine-Kohlbrecher et al. (2010) - Mentioned in context 3 [5] Associated abnormalities may include facial dysmorphism, neurological signs and symptoms, behavioral problems, and abnormalities of various other organ systems. (Context 6) [8] X-linked intellectual disability refers to medical disorders associated with X-linked recessive inheritance that result in intellectual disability. (Context 8) [9] Most affected children have weak muscle tone (hypotonia), which delays motor skills such as sitting, standing, and walking. Some people with ... (Context 9)

Non-syndromic X-linked intellectual disability (NS-XLMR) can be diagnosed through various diagnostic tests, including:

• Chromosomal microarray analysis (CMA): This is a first-line genetic test recommended by medical genetics groups to identify genetic mutations in children with NS-XLMR [5]. CMA can detect deletions or duplications of genetic material on the X-chromosome.
• Genetic testing: Genetic testing can help diagnose the specific type of intellectual disability present and guide treatment. Early intervention can significantly benefit individuals with NS-XLMR [8].
• Next Generation Sequencing (NGS): This molecular test is used to identify disease-causing mutations within a family, allowing for carrier testing and prenatal diagnosis [14].

In addition to these tests, other diagnostic approaches may include:

• Karyotype analysis: This can help identify chromosomal abnormalities that may be associated with NS-XLMR.
• Fragile X syndrome testing: Since Fragile X syndrome is the most common cause of inherited intellectual disability, testing for this condition may also be considered.

It's essential to note that a diagnosis of NS-XLMR should only be made by a qualified healthcare professional after a comprehensive evaluation and diagnostic workup.

Current Status of Drug Treatment for Non-Syndromic X-linked Intellectual Disability

While there are no specific pharmacologic treatments available for cognitive impairment in individuals with non-syndromic X-linked intellectual disability (NS-XLID), research continues to explore potential therapeutic options.

• General principles for antiepileptic drug treatment involve selecting a medication based on the individual's specific needs and medical history. However, these principles are not specifically tailored for NS-XLID.
• The discovery of new genes associated with X-linked intellectual disability has opened up possibilities for targeted therapies. For instance, research on the CNKSR2 gene has identified potential therapeutic targets for treating NS-XLID.
• Studies have shown that non-syndromic intellectual disability is extremely heterogeneous and contributes more than X-linked ID to the overall burden of intellectual disability. This heterogeneity makes it challenging to develop effective pharmacologic treatments.

Current Research and Future Directions

Research on non-syndromic X-linked intellectual disability continues to uncover new genes and potential therapeutic targets. For example, recent studies have identified genes involved in transcription process, mitochondrial function, glycoprotein metabolism, and ubiquitination as contributing factors to NS-XLID.

• New genes associated with X-linked intellectual disability include those involved in the transcription process, mitochondrial function, glycoprotein metabolism, and ubiquitination. These findings provide new avenues for research into potential therapeutic options.
• The development of targeted therapies will require a better understanding of the underlying genetic mechanisms contributing to NS-XLID.

Conclusion

While there are no specific pharmacologic treatments available for cognitive impairment in individuals with non-syndromic X-linked intellectual disability, ongoing research continues to explore potential therapeutic options. Further studies on the genetics and molecular mechanisms underlying NS-XLID will be crucial in developing effective targeted therapies.

References:

• [8] Nov 16, 2021 — No specific pharmacologic treatment is available for cognitive impairment in the developing child or adult with intellectual disability (ID).
• [12] Table 2 Genes that have been implicated in non-syndromic X-linked mental retardation ... possibilities for drug treatment of these disorders. ...
• [15] Genes that are involved in the transcription process, mitochondrial function, glycoprotein metabolism, and ubiquitination dominate the list of 21 new genes associated with X-linked intellectual disability since the last update in 2017.

Non-syndromic X-linked intellectual disability (NS-XLID) can be challenging to diagnose due to its complex nature and the involvement of multiple genes on the X-chromosome. However, there are several differential diagnoses that should be considered when evaluating individuals with NS-XLID.

Other forms of X-linked ID

• Other forms of X-linked intellectual disability should be