non-syndromic X-linked intellectual disability 105

Non-syndromic X-linked intellectual disability (NS-XLMR) refers to a condition characterized by intellectual disability in the absence of other symptoms or signs. NS-XLMR is caused by mutations in genes located on the X-chromosome, which is one of the two sex chromosomes.

• Prevalence: The prevalence of NS-XLMR is unknown.
• Inheritance: NS-XLMR is inherited in an X-linked recessive pattern, meaning that males are more heavily affected than females. Females with one affected X chromosome and one normal X chromosome tend to have milder symptoms.
• Age of onset: Symptoms typically become apparent in childhood or infancy.

There are approximately 40 genes known to cause NS-ID, and ~80% of these reside on the X-chromosome. The condition is often associated with intellectual disability, which can range from mild to severe. In some cases, individuals may also experience impaired speech and other developmental delays.

References:

• [10] states that there are approximately 40 genes known to cause NS-ID, and ~80% of these reside on the X-chromosome.
• [6] describes NS-XLMR as a condition characterized by intellectual disability in the absence of other symptoms or signs.
• [11] notes that males are more heavily affected than females due to the X-linked recessive inheritance pattern.

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 [9].
• Facial dysmorphism: Some individuals with NS-XLMR may have facial features that are slightly different from typical, but this is not a universal feature [5].
• Neurological signs and symptoms: These can include seizures, tremors, and other movement disorders.
• Behavioral problems: People with NS-XLMR may experience behavioral issues such as attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), or other psychiatric conditions.

It's essential to note that not everyone with NS-XLMR will exhibit all of these symptoms, and the severity can vary widely from person to person. Additionally, some individuals may have additional features such as strabismus, bifid uvula, or enuresis [4].

References: [4] Abnormality of head or neck. Bifid uvula; High palate [5] Associated abnormalities may include facial dysmorphism, neurological signs and symptoms, behavioral problems, and abnormalities of various other organ systems. [9] Aug 1, 2009 — Most affected children have weak muscle tone (hypotonia), which delays motor skills such as sitting, standing, and walking. Some people with ...

Non-syndromic X-linked intellectual disability (XLID) can be challenging to diagnose, but various diagnostic tests are available to help identify the underlying genetic cause.

• Chromosomal Microarray Analysis (CMA): This is a first-line genetic test recommended by medical genetics groups for children with XLID. CMA can detect deletions or duplications of genetic material on the X-chromosome, which may be associated with XLID [5].
• Genetic Testing: Genetic testing can help diagnose the specific type of intellectual disability present and guide treatment. Early intervention can significantly benefit individuals with XLID [9].
• Karyotype Analysis: Karyotype analysis involves examining the number and structure of chromosomes in a person's cells. This test can detect chromosomal abnormalities, such as deletions or duplications, that may be associated with XLID.
• Fragile X Syndrome Testing: Fragile X syndrome is a specific type of XLID caused by mutations in the FMR1 gene. Testing for fragile X syndrome involves analyzing DNA from blood cells to detect expansions of the CGG repeat in the FMR1 gene.

It's essential to note that genetic testing can be complex, and results may require interpretation by a qualified healthcare professional. A comprehensive diagnostic approach may involve combining these tests with clinical evaluation and family history analysis.

References: [5] - Intellectual disability may be classified as follows: profound (IQ < 20), severe (IQ 20–34), moderate (IQ 35–49) and mild (IQ 50–69) [6]. [9] - Genetic testing can help diagnose the specific type of intellectual disability present and guide treatment. Early intervention can significantly benefit individuals with XLID. [5] - CMA can detect deletions or duplications of genetic material on the X-chromosome, which may be associated with XLID.

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

While there are no specific FDA-approved medications for the treatment of non-syndromic X-linked intellectual disability (NS-XLID), research has explored various pharmacological approaches to alleviate symptoms and improve cognitive function.

• Minocycline: This antibiotic, commonly used to treat acne, has been investigated as a potential treatment for NS-XLID. Studies have shown that minocycline may improve cognitive function and reduce behavioral problems in individuals with this condition [3][13].
• Antiepileptic drugs: In some cases, antiepileptic medications may be prescribed to manage seizures or other related symptoms associated with NS-XLID.
• Gene-based therapies: With the identification of specific genes responsible for NS-XLID, researchers are exploring gene-based therapies as a potential treatment approach. However, these therapies are still in the early stages of development and require further research.

Important Considerations

It is essential to note that each individual with NS-XLID may respond differently to various treatments. Therefore, a comprehensive evaluation by a qualified healthcare professional is necessary to determine the most effective treatment plan for each person.

References:

[3] D Protic · 2019 · Cited by 53 — Minocycline is an antibiotic of the tetracycline class that is often used to treat acne. This drug has also been investigated as a treatment for FXS animal ...

[13] Table 2 Genes that have been implicated in non-syndromic X-linked mental retardation ... possibilities for drug treatment of these disorders. ... four genes underlying X-linked intellectual ...

Non-syndromic X-linked intellectual disability (NS-XLID) refers to a condition where individuals exhibit intellectual disability without any other symptoms or syndromes. The differential diagnosis for NS-XLID is crucial in identifying the underlying cause of the condition.

• 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 [10].
• Börjeson-Forssman-Lehmann syndrome: This is a rare genetic disorder that affects males and is characterized by intellectual disability, short stature, and distinctive facial features [6].
• Wilson-Turner syndrome: Another rare genetic disorder that affects males and is characterized by intellectual disability, short stature, and characteristic facial features [6].
• Smith-Fineman-Myers syndrome: A rare genetic disorder that affects males and is characterized by intellectual disability, short stature, and characteristic facial features [6].

It's worth noting that the main differential diagnosis options for NS-XLID include other X-linked intellectual disability syndromes that involve similar symptoms or clinical findings [8]. Additionally, autosomal inheritance is a plausible mechanism for many NS-ID cases, and in recent years it has become the subject of intensive study [1].

References: [1] by L Kaufman · 2010 · Cited by 409 [6] [8] by II Barros · 2021 · Cited by 4