non-syndromic X-linked intellectual disability 91

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 [1][2][3], NS-XLMR is characterized by:

• Intellectual disability as the only symptom
• No associated physical, neurological, or psychiatric manifestations
• Males are more heavily affected than females, who tend to have milder symptoms due to having one normal X chromosome

There are approximately 40 genes known to cause NS-ID, and ~80% of these reside on the X-chromosome [4]. The new genes were identified by sequencing of candidate genes, the entire X-chromosome, the whole exome, or the whole genome [5].

It's worth noting that non-syndromic intellectual disabilities are typified by a lack of other abnormalities (syndromic X-linked intellectual developmental disabilities are generally associated with additional physical, neurological, and/or metabolic abnormalities) [6].

Non-syndromic X-linked intellectual disability (NS-XLMR) is a complex neurodevelopmental disorder that can manifest in various ways. While the exact signs and symptoms may vary from person to person, here

Non-syndromic X-linked intellectual disability (NS-XLMR) 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 suspected NS-XLMR. CMA can detect deletions or duplications of genetic material on the X chromosome, which may be associated with intellectual disability [5].
• Genetic testing: Specific genetic tests are available to identify mutations in genes known to cause NS-XLMR. These tests can help diagnose the specific type of intellectual disability present and guide treatment.
• Karyotype analysis: This test examines the number and structure of chromosomes, which can reveal abnormalities such as deletions or duplications that may contribute to NS-XLMR [11].
• Next Generation Sequencing (NGS): This advanced genetic testing technique allows for the simultaneous analysis of multiple genes, including those on the X chromosome. NGS can be used to identify mutations in genes associated with NS-XLMR and is often used in conjunction with other diagnostic tests.

It's essential to note that a diagnosis of NS-XLMR should only be made by a qualified healthcare professional after comprehensive evaluation and testing. Early intervention and genetic counseling can significantly benefit individuals and families affected by this condition [9].

References: [5] - Medical genetics groups recommend chromosomal microarray analysis (CMA) as a first-line genetic test to identify genetic mutations in children with NS-XLMR. [9] - Genetic testing can help diagnose the specific type of intellectual disability present and guide treatment. Early intervention can significantly benefit individuals and families affected by this condition. [11] - Karyotype analysis examines the number and structure of chromosomes, which can reveal abnormalities such as deletions or duplications that may contribute to NS-XLMR.

Differential Diagnosis of Non-Syndromic X-Linked Intellectual Disability

Non-syndromic X-linked intellectual disability (NS-XLID) is a condition characterized by intellectual disability in the absence of other symptoms or physical anomalies. When diagnosing NS-XLID, it's essential to consider various differential diagnoses that can present with similar symptoms.

Other Forms of X-Linked ID

• Other forms of X-linked intellectual disability should be considered in the differential diagnosis, as they may present with similar symptoms.
• These conditions include other X-linked ID syndromes that involve similar symptoms or clinical findings. [7]
• The main differential diagnosis options include other X-linked intellectual disability syndromes that involve similar symptoms or clinical findings. [7]

Autism Spectrum Disorder and Borderline Intellectual Functioning

• Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by difficulties with social interaction, verbal and nonverbal communication, and repetitive behaviors.
• Borderline intellectual functioning refers to individuals who have an IQ score between 70-84, which may indicate mild cognitive impairment. [5]

Child Abuse & Neglect, Posttraumatic Stress Disorder

• Child abuse and neglect can lead to intellectual disability in some cases, particularly if the abuse is severe or prolonged.
• Posttraumatic stress disorder (PTSD) can also be a contributing factor to intellectual disability in individuals who have experienced traumatic events. [5]

Börjeson-Forssman-Lehmann Syndrome, Wilson-Turner Syndrome, and Smith-Fineman-Myers Syndrome

• Börjeson-Forssman-Lehmann syndrome is a rare genetic disorder characterized by intellectual disability, short stature, and distinctive facial features.
• Wilson-Turner syndrome is another rare genetic disorder that presents with intellectual disability, short stature, and characteristic facial features.
• Smith-Fineman-Myers syndrome is a rare genetic disorder that involves intellectual disability, short stature, and distinctive facial features. [6]

ATR-X Syndrome

• ATR-X syndrome is a rare genetic disorder characterized by intellectual disability, characteristic facial features, abnormalities of the genitourinary tract, and alpha thalassemia.
• This condition should be considered in the differential diagnosis of NS-XLID, as it presents with similar symptoms. [9]

Fragile X Syndrome

• Fragile X syndrome is a genetic disorder caused by mutations in the FMR1 gene, leading to intellectual disability and other physical characteristics.
• This condition is the most common form of inherited intellectual disability, affecting approximately 1:5000 males. Females are usually non- or mildly affected. [13]

Increased Gene Dosage

• Increased gene dosage has been observed in males with non-syndromic mild to moderate ID with speech delay.
• This condition should be considered in the differential diagnosis of NS-XLID, as it presents with similar symptoms. [14]