non-syndromic X-linked intellectual disability 92

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 can be caused by mutations in approximately 40 genes known to cause non-syndromic intellectual disability, with around 80% of these genes residing on the X-chromosome. The prevalence and inheritance pattern of NS-XLMR are not well established.

Some specific forms of NS-XLMR include:

• Non-syndromic X-linked intellectual disability 14 (MRX14), which is characterized by moderate intellectual disability and impaired speech [6].
• Non-syndromic ID caused by mutations in the DLG3 gene [7].
• Rare non-syndromic intellectual disability, a rare hereditary neurologic disease characterized by early-onset cognitive impairment as a sole disability [9].

It's worth noting that females with NS-XLMR tend to have milder symptoms than males due to X-chromosome inactivation [11].

Non-syndromic X-linked intellectual disability (NS-XLMR) presents with a range of signs and symptoms, primarily affecting cognitive development.

• Intellectual Disability: The most common symptom is intellectual disability, which can vary in severity [1][5].
• Weak Muscle Tone (Hypotonia): Many affected individuals have weak muscle tone, leading to delayed motor skills such as sitting, standing, and walking [9].
• Speech Development Delay: Speech development may be delayed or impaired in some cases [7].
• Average Head Circumference: Affected individuals often have average head circumferences [7].

It's essential to note that NS-XLMR can manifest differently in each individual. Some people might experience additional symptoms, such as:

• Facial dysmorphism
• Neurological signs and symptoms
• Behavioral problems
• Abnormalities of various other organ systems

However, these symptoms are not universal and may vary depending on the specific genetic mutation causing the condition [6][8].

References: [1] - Context 15 [5] - Context 15 [7] - Context 7 [9] - Context 9

Non-syndromic X-linked intellectual disability (NS-XLMR) can be challenging to diagnose, but various diagnostic tests are available to help identify the condition.

Chromosomal Microarray Analysis (CMA) is now recommended as a first-line genetic test by medical genetics groups for children with suspected NS-XLMR. This test can help identify genetic mutations that may be causing the intellectual disability [5].

Additionally, genetic testing can also be used to diagnose specific types of NS-XLMR and guide treatment. Early intervention can significantly benefit individuals with intellectual disabilities.

In some cases, karyotype analysis or Fragile X syndrome testing may also be recommended to rule out other conditions that could be causing the intellectual disability [10].

It's essential to note that a comprehensive diagnostic evaluation should include a thorough medical history, physical examination, and cognitive assessment. A team of healthcare professionals, including geneticists, psychologists, and neurologists, may work together to provide an accurate diagnosis and develop a treatment plan.

References:

• Chromosomal microarray analysis (CMA) is recommended as a first-line genetic test for children with suspected NS-XLMR [5].
• Genetic testing can help diagnose specific types of NS-XLMR and guide treatment [9].
• Karyotype analysis or Fragile X syndrome testing may be recommended to rule out other conditions that could be causing the intellectual disability [10].

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

• Nonsyndromic XLID is characterized by intellectual disability in the absence of other symptoms [3]. Other differential diagnoses include other forms of X-linked ID, which can present with similar clinical features.
• The main differential diagnosis options include other X-linked intellectual disability syndromes that involve similar symptoms or clinical findings [8].

Genetic disorders

• Fragile X syndrome is a well-known cause of NS-XLID, and its prevalence in affected sib pairs and X-linked families is approximately 12/45 (27%) [11].
• Mutations in other genes on the X-chromosome, such as HUWE1 variants or rearrangements, can also lead to NS-XLID [9].
• Intellectual disability multigene panels that include TRIO and other genes should be considered in the differential diagnosis of individuals with NS-ID [13].

Other conditions

• Autism Spectrum Disorder (ASD), Borderline intellectual functioning, Child Abuse & Neglect, Posttraumatic Stress Disorder, Börjeson-Forssman-Lehmann syndrome, Wilson-Turner syndrome, and Smith-Fineman-Myers syndrome are some of the differential diagnoses that should be considered [6].

It's essential to note that a comprehensive evaluation, including genetic testing and clinical assessment, is necessary to accurately diagnose NS-XLID and rule out other potential causes.

References:

[3] Nonsyndromic XLID is characterized by intellectual disability in the absence of other symptoms. [8] The main differential diagnosis options include other X-linked intellectual disability syndromes that involve similar symptoms or clinical findings. [9] The association of HUWE1 variants or rearrangements with X-linked intellectual disability (XLID) is now well recognised. [11] The prevalence of Fragile X syndrome in affected sib pairs and X linked families is approximately 12/45 (27%). [13] An intellectual disability multigene panel that includes TRIO and other genes should be considered in the differential diagnosis.