non-syndromic X-linked intellectual disability 72

Non-syndromic X-linked intellectual disability (NS-XLMR) refers to a condition where males have intellectual disability without any additional physical, neurological, or psychiatric symptoms. This type of intellectual disability is caused by mutations in genes located on the X-chromosome.

According to various sources [4][5][10], NS-XLMR is characterized by:

• Intellectual disability that affects only males
• No additional physical, neurological, or psychiatric symptoms
• The condition is inherited in an X-linked recessive pattern, meaning that females are typically carriers and may have mild symptoms

It's worth noting that the prevalence of NS-XLMR is unknown [5], and there are approximately 40 genes known to cause this type of intellectual disability, with around 80% of these genes residing on the X-chromosome [10].

References: [4] - Context result 7 [5] - Context result 5 [10] - Context result 10

Non-syndromic X-linked intellectual disability (NS-XLMR) is a condition characterized by intellectual disability in the absence of other symptoms or signs. The signs and symptoms of NS-XLMR can vary from person to person, but some common features include:

• Intellectual disability: This is the primary symptom of NS-XLMR, with affected individuals typically having an IQ below 70.
• Weak muscle tone (hypotonia): Many people with NS-XLMR have weak muscle tone, which can delay motor skills such as sitting, standing, and walking [8].
• Delayed speech development: Some individuals with NS-XLMR may experience delayed or absent speech development [7].
• Average head circumference: Affected individuals typically have average head circumferences [7].

It's worth noting that not all people with NS-XLMR will exhibit these symptoms, and the severity of the condition can vary widely from person to person. Additionally, some individuals may have other subtle features or signs that are not immediately apparent.

In terms of specific physical characteristics, some people with NS-XLMR may experience:

• Abnormality of head or neck: This can include bifid uvula or high palate [4].
• Strabismus (crossed eyes): Some individuals with NS-XLMR may have strabismus [4].
• Enuresis (bedwetting): Affected individuals may experience enuresis, particularly in childhood [4].

It's essential to remember that these symptoms can vary widely from person to person and are not present in all cases of NS-XLMR. A comprehensive medical evaluation is necessary for an accurate diagnosis.

References: [4] - Abnormality of head or neck, strabismus, abnormality of the genitourinary system, enuresis. [7] - All affected individuals had average head circumferences and could not learn to read or write. All affected family members' speech development was delayed. [8] - Most affected children have weak muscle tone (hypotonia), which delays motor skills such as sitting, standing, and walking.

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

• Sequence analysis: This test involves analyzing the entire coding region of specific genes associated with NS-XLMR. Sequence analysis can identify mutations in these genes that may cause the condition.
• Next-Generation Sequencing (NGS): NGS is a powerful tool for identifying genetic variants, including those that cause NS-XLMR. This test can analyze multiple genes simultaneously and provide comprehensive information about the genetic basis of the condition.
• Massively Parallel Sequencing (MPS): MPS is another type of sequencing technology that can be used to diagnose NS-XLMR. This test involves analyzing large numbers of DNA sequences in parallel, which can help identify genetic variants associated with the condition.

These diagnostic tests are typically performed by specialized laboratories and may involve a combination of sequence analysis and NGS/MPS technologies. The specific test used will depend on the individual's clinical presentation and family history.

According to [6], integrated disease information for Non-Syndromic X-Linked Intellectual Disability, including associated genes, mutations, phenotypes, pathways, drugs, and more - integrated from 75 data sources, genetic tests for NS-XLMR are available in various laboratories around the world. These tests can provide valuable information about the genetic basis of the condition and help guide clinical management.

In addition to these diagnostic tests, other resources such as GeneReviews, PubMed, MedlinePlus, and practice guidelines may also be useful in managing individuals with NS-XLMR [5].

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

Unfortunately, there is no specific pharmacologic treatment available for cognitive impairment in individuals with non-syndromic X-linked intellectual disability (NS-XLID) [8]. However, research has identified several genes associated with NS-XLID that may provide potential targets for drug treatment.

Genetic Basis and Potential Targets

Studies have implicated various genes in the development of NS-XLID, including those involved in transcription process, mitochondrial function, glycoprotein metabolism, and ubiquitination [15]. These findings suggest that targeted therapies may be developed to address specific aspects of cognitive impairment associated with NS-XLID.

Emerging Therapeutic Approaches

While there is no established drug treatment for NS-XLID, emerging therapeutic approaches aim to target the underlying genetic mechanisms. For instance, research on Fragile X syndrome (FXS), a related condition, has led to the development of pharmacological interventions aimed at reducing cognitive impairment [11].

Future Directions and Research Needs

Further research is necessary to fully understand the genetic basis of NS-XLID and to develop effective therapeutic strategies. The identification of new genes associated with NS-XLID, such as CNKSR2 and IL1RAPL1, may provide valuable insights into potential drug targets [13][14].

References:

[8] Nov 16, 2021 — No specific pharmacologic treatment is available for cognitive impairment in the developing child or adult with intellectual disability (ID).

[11] Fragile X syndrome (FXS) is an X-linked triplet repeat expansion disorder caused by the unstable expansion of CGG repeats in the 5' untranslated region of the FMR1 gene.

[13] Loss-of-Function CNKSR2 Mutation Is a Likely Cause of Non-Syndromic X-Linked Intellectual Disability.62: Houge G...Hovland R: 22511892: 2012: 19

[14] Deletion of the immunoglobulin domain of IL1RAPL1 results in nonsyndromic X-linked intellectual disability associated with behavioral problems and mild dysmorphism.62: Franek KJ...Schwartz CE ...

[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-XLMR) has a complex differential diagnosis, involving various conditions that can present with similar symptoms or clinical findings.

• Other forms of X-linked ID: These include conditions such as ATR-X syndrome, which is characterized by intellectual disability, characteristic facial features, abnormalities of the genitourinary tract and alpha thalassemia [9].
• Fragile X syndrome: This is a genetic disorder caused by mutations in the FMR1 gene, leading to intellectual disability, behavioral problems, and physical characteristics such as long face and large testicles. It is the most common form of ID, with a prevalence of around 1:5000 males [15].
• Other X-linked intellectual disability syndromes: These include conditions such as Börjeson-Forssman-Lehmann syndrome, Wilson-Turner syndrome, and Smith-Fineman-Myers syndrome, which can present with similar symptoms or clinical findings to NS-XLMR [6].

It's worth noting that the differential diagnosis of NS-XLMR is complex and requires a comprehensive evaluation of the individual's medical history, physical examination, and laboratory tests. A thorough diagnostic workup should include genetic testing for known X-linked intellectual disability genes, as well as other conditions that can present with similar symptoms.

References:

• [9] ATR-X syndrome
• [6] Börjeson-Forssman-Lehmann syndrome, Wilson-Turner syndrome, and Smith-Fineman-Myers syndrome
• [15] Fragile X syndrome