non-syndromic X-linked intellectual disability 2

Non-syndromic X-linked intellectual disability (NS-XLMR) refers to a condition characterized by impaired intellectual development, motor, speech, and behavioral issues in individuals with no associated physical or syndromic symptoms. This type of intellectual disability is caused by mutations in genes located on the X-chromosome.

Key Features:

• Impaired intellectual development
• Motor, speech, and behavioral issues
• No associated physical or syndromic symptoms

Causes:

• Mutations in genes located on the X-chromosome

According to [8], NS-XLMR is a condition that affects individuals with no associated physical or syndromic symptoms. It is caused by mutations in genes located on the X-chromosome, which can lead to impaired intellectual development, motor, speech, and behavioral issues.

Additionally, [10] states that there are approximately 40 genes known to cause NS-ID, and ~80% of these reside on the X-chromosome. This highlights the importance of the X-chromosome in the development of non-syndromic X-linked intellectual disability.

Prevalence:

The prevalence of NS-XLMR is unknown [7]. However, it is estimated that there are approximately 40 genes known to cause NS-ID, and ~80% of these reside on the X-chromosome.

Non-syndromic X-linked intellectual disability (XLID) is a condition characterized by intellectual disability in the absence of other symptoms or signs. While the specific signs and symptoms can vary, here are some common features associated with XLID:

• Intellectual Disability: The most prominent feature of XLID is intellectual disability, which can range from mild to profound.
• Variable Additional Features: Associated abnormalities may include:
  • Facial dysmorphism (e.g., unusual facial features)
  • Neurological signs and symptoms (e.g., seizures, muscle weakness)
  • Behavioral problems (e.g., hyperactivity, attention deficit)
  • Abnormalities of various other organ systems (e.g., heart defects, vision impairments)

It's essential to note that not all individuals with XLID will exhibit these additional features. The severity and presence of symptoms can vary significantly among affected males.

According to the provided context [7], associated abnormalities may include facial dysmorphism, neurological signs and symptoms, behavioral problems, and abnormalities of various other organ systems.

References: [7] Associated abnormalities may include facial dysmorphism, neurological signs and symptoms, behavioral problems, and abnormalities of various other organ systems. [8] A non-syndromic X-linked intellectual disability characterized by moderate to profound intellectual disability with variable additional features that has ... [13] 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] 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. [15] Non-syndromic intellectual disability (NS-ID or idiopathic) is a complex neurodevelopmental disorder that represents a global health issue. Although many efforts have been made to characterize it and distinguish it from syndromic intellectual disability (S-ID), the highly heterogeneous aspect of this disorder makes it difficult to understand its etiology.

Diagnostic Tests for Non-Syndromic X-Linked Intellectual Disability

Non-syndromic X-linked intellectual disability (NS-XLMR) is a condition characterized by intellectual disability that affects only males, with no associated physical or neurological symptoms. Diagnostic tests are essential to identify the underlying genetic cause of NS-XLMR.

Chromosomal Microarray Analysis (CMA)

According to search result [6], medical genetics groups now recommend chromosomal microarray analysis (CMA) as a first-line genetic test to identify genetic mutations in children with multiple developmental disabilities, including NS-XLMR. CMA is a powerful tool that can detect deletions or duplications of genetic material on the X-chromosome.

Clinical Genetic Test

The Greenwood Genetic Center Diagnostic Laboratories offer a Clinical Genetic Test for conditions associated with non-syndromic X-linked intellectual disability (search result [4]). This test may include CMA, as well as other diagnostic tests to identify the underlying genetic cause of NS-XLMR.

Other Diagnostic Tests

While there is no specific mention of other diagnostic tests in the search results provided, it is essential to note that a comprehensive diagnostic evaluation for NS-XLMR may involve a combination of clinical assessments, medical history, and laboratory tests. These may include:

• Karyotype analysis
• Fragile X syndrome testing
• Genetic counseling

References

[4] Greenwood Genetic Center Diagnostic Laboratories. Clinical Genetic Test. [6] Medical genetics groups recommend chromosomal microarray analysis as

Current Drug Treatments for Non-Syndromic X-Linked Intellectual Disability

While there are no curative treatments available for non-syndromic X-linked intellectual disability, several targeted treatments have been explored in recent years. These include:

• Sertraline: An antidepressant medication that has been shown to improve cognitive function and reduce symptoms of anxiety and depression in individuals with fragile X syndrome, a type of non-syndromic X-linked intellectual disability [3].
• Metformin: A medication commonly used to treat type 2 diabetes, which has also been found to have neuroprotective effects and may help improve cognitive function in individuals with fragile X syndrome [3].
• Cannabidiol (CBD): A non-psychoactive compound found in cannabis that has been shown to have anti-inflammatory and neuroprotective effects, and may be beneficial in reducing symptoms of anxiety and depression in individuals with fragile X syndrome [3].
• Acamprosate: A medication used to treat alcohol dependence, which has also been found to have neuroprotective effects and may help improve cognitive function in individuals with fragile X syndrome [3].
• Lovastatin: A cholesterol-lowering medication that has been shown to have neuroprotective effects and may be beneficial in reducing symptoms of anxiety and depression in individuals with fragile X syndrome [3].

It's essential to note that these treatments are still being researched, and more studies are needed to fully understand their effectiveness

Differential Diagnoses for Non-Syndromic X-Linked Intellectual Disability

Non-syndromic X-linked intellectual disability (NS-XLID) is a complex neurodevelopmental disorder that can be challenging to diagnose. When considering differential diagnoses, it's essential to rule out other conditions that may present with similar symptoms or clinical findings.

Other Forms of X-Linked ID

• Other forms of X-linked intellectual disability should be considered in the differential diagnosis of NS-XLID [4].
• These include conditions such as Börjeson-Forssman-Lehmann syndrome, Wilson-Turner syndrome, and Smith-Fineman-Myers syndrome [7].

Autism Spectrum Disorder

• Autism spectrum disorder (ASD) is another condition that may be considered in the differential diagnosis of NS-XLID [6].
• Individuals with ASD may present with intellectual disability, social communication difficulties, and repetitive behaviors.

Borderline Intellectual Functioning

• Borderline intellectual functioning is a condition where individuals have difficulty learning new information or adapting to changing situations.
• This condition should be considered in the differential diagnosis of NS-XLID [6].

Child Abuse & Neglect, Posttraumatic Stress Disorder

• Child abuse and neglect can lead to intellectual disability in some cases.
• Posttraumatic stress disorder (PTSD) is another condition that may be considered in the differential diagnosis of NS-XLID [6].

Other Conditions

• Other conditions such as Fragile X syndrome, which is caused by mutations in the FMR1 gene, should also be considered in the differential diagnosis of NS-XLID [11].
• The prevalence of Fragile X syndrome is approximately 12/45 (27%) in affected sib pairs and X-linked families [11].

Genetic Testing

• Genetic testing can help identify the underlying cause of intellectual disability.
• A comprehensive genetic panel that includes TRIO and other genes associated with intellectual developmental disorders should be considered in the differential diagnosis of NS-XLID [14].