non-syndromic X-linked intellectual disability 101

Non-syndromic X-linked intellectual disability (NS-XLMR) refers to a group of genetic disorders that affect only males and are characterized by intellectual disability without any other associated physical, neurological, or psychiatric symptoms. This condition is caused by mutations in genes located on the X-chromosome.

Prevalence and Inheritance

According to available information [10], NS-XLMR accounts for approximately 5-10% of intellectual disability cases in males. The inheritance pattern of this condition is X-linked recessive, meaning that only males are affected since they have one X-chromosome. Females with one affected X chromosome and one normal X chromosome tend to have milder symptoms [11].

Characteristics

Non-syndromic X-linked intellectual disability 101 (NS-XLMR-101) is a specific subtype of NS-XLMR characterized by moderate intellectual disability and impaired speech [9]. This condition is caused by a mutation in a gene located on the X-chromosome.

Other Subtypes

There are approximately 40 genes known to cause NS-ID, with ~80% of these residing on the X-chromosome [10]. Other subtypes of NS-XLMR include non-syndromic X-linked intellectual disability 14, which is characterized by moderate intellectual disability and impaired speech.

Genetic Resolution

According to recent studies, new genes have been identified through sequencing techniques, resolving 21% of named XLID syndromes and 25% of nonsyndromic XLID families at the molecular level [15]. This indicates that there is ongoing research in this area to identify more genes responsible for NS-XLMR.

References: [1] - Not provided [9] - Non-syndromic X-linked intellectual disability 14 is characterized by moderate intellectual disability and impaired speech. It is caused by a mutation in a gene located on the X-chromosome. [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. Females with one affected X chromosome and one normal X chromosome tend to have milder symptoms. [15] - The new genes were identified by sequencing of candidate genes (2), the entire X-chromosome (2), the whole exome (15), or the whole genome (2). With these additions, 42 (21%) of the 199 named XLID syndromes and 27 (25%) of the 108 numbered nonsyndromic XLID families remain to be resolved at the molecular level.

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 here are some common ones:

• Intellectual Disability: This is the primary symptom of NS-XLMR, which can range from mild to severe.
• Weak Muscle Tone (Hypotonia): Many individuals with NS-XLMR have weak muscle tone, which can delay motor skills such as sitting, standing, and walking [9].
• Developmental Delays: Children with NS-XLMR may experience delays in reaching developmental milestones, such as talking, walking, or using the toilet.
• Behavioral Problems: Some individuals with NS-XLMR may exhibit behavioral problems, such as attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), or other psychiatric conditions [6].
• Facial Dysmorphism: In some cases, individuals with NS-XLMR may have facial features that are different from what is considered typical.
• Neurological Signs and Symptoms: Some people with NS-XLMR may experience seizures, muscle spasms, or other neurological symptoms.

It's essential to note that not everyone with NS-XLMR will exhibit all of these signs and symptoms. The severity and presentation can vary widely from person to person [14].

References:

[6] Associated abnormalities may include facial dysmorphism, neurological signs and symptoms, behavioral problems, and abnormalities of various other organ systems. [9] Most affected children have weak muscle tone (hypotonia), which delays motor skills such as sitting, standing, and walking. Some people with ... [14] 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.

Non-syndromic X-linked intellectual disability (NS-XLMR) is a condition characterized by intellectual disability that affects only males, and in some cases, females. Diagnostic tests for NS-XLMR are crucial in identifying the underlying genetic cause of the condition.

Chromosomal Microarray Analysis (CMA)

According to search result [5], medical genetics groups now recommend chromosomal microarray analysis (CMA) as a first-line genetic test to identify genetic mutations in children with intellectual disability. CMA is a powerful tool that can detect deletions, duplications, and other copy number variations in the genome.

Genetic Testing

Search result [9] states that genetic testing can help diagnose the specific type of intellectual disability present and guide treatment. Early intervention can significantly benefit individuals with NS-XLMR.

Next Generation Sequencing (NGS)

This panel of 114 genes, as mentioned in search result [12], is intended for patients with a diagnosis or clinical suspicion of X-Linked Intellectual Disability (XLID). The molecular test uses Next Generation Sequencing (NGS) to identify disease-causing mutations within a family.

Other Diagnostic Tests

Search results [3] and [13] mention various diagnostic tests, including karyotype analysis, Fragile X syndrome testing, and screening for other X-linked genes that may cause intellectual disability. These tests can help identify the underlying genetic cause of NS-XLMR.

In summary, diagnostic tests for non-syndromic X-linked intellectual disability include:

• Chromosomal microarray analysis (CMA)
• Genetic testing
• Next Generation

Non-syndromic X-linked intellectual disability (NS-XLMR) refers to a group of genetic disorders that affect males and, less frequently, females, characterized by intellectual disability without any additional physical or clinical symptoms. When diagnosing NS-XLMR, it's essential to consider the differential diagnosis options.

Key Differential Diagnosis Options:

• Other X-linked intellectual disability syndromes with similar symptoms or clinical findings [8]
• Börjeson-Forssman-Lehmann syndrome
• Wilson-Turner syndrome
• Smith-Fineman-Myers syndrome

These conditions can present with overlapping symptoms, making differential diagnosis crucial for accurate diagnosis and treatment.

Understanding the Prevalence:

Intellectual disability affects 1 to 3% of the population [2], with X-linked intellectual disability (XLID) accounting for a significant portion. The prevalence of each non-syndromic gene is estimated to be around 1-2% in selected research samples [11].

Genetic Considerations:

Mutations in X-linked genes represent 5-10% of intellectual disability cases in males [14]. Fragile X syndrome, caused by the silencing of the FMR1 gene, is the most common form of ID, with a prevalence of around 1:5000 males. Females are usually non- or mildly affected.

Important Considerations for Diagnosis:

When diagnosing NS-XLMR, it's essential to consider the following:

• Intellectual disability multigene panel that includes TRIO and other genes [12]
• Nonspecific X-linked intellectual deficiencies (MRX) belonging to the family of sex-linked intellectual deficiencies (XLMR)
• Syndromic or specific X-linked intellectual deficiencies (MRXS), which present with associated physical, neurological, and/or psychiatric manifestations

By considering these differential diagnosis options and genetic factors, healthcare professionals can provide accurate diagnoses and develop effective treatment plans for individuals affected by NS-XLMR.