chromosome 16p11.2 deletion syndrome, 220-kb

Chromosome 16p11.2 Deletion Syndrome: A Rare Genetic Condition

Chromosome 16p11.2 deletion syndrome is a rare genetic condition caused by the deletion of a small piece of DNA on the short arm (p) of chromosome 16 at location 11.2 [1]. This deletion occurs in approximately 1% of autism spectrum disorder cases and is estimated to account for about 1% of all developmental delay cases [3][4].

Characteristics of the Condition

Individuals with chromosome 16p11.2 deletion syndrome often experience global developmental delay, intellectual disability, and childhood-onset obesity [1]. The condition is also associated with autism spectrum disorders, mild variable dysmorphism (physical abnormalities), and predisposition to obesity [3][4].

Neurological Phenotypes

Comprehensive neurologic evaluations have shown that individuals with chromosome 16p11.2 deletion syndrome often experience speech and motor impairments, growth abnormalities, and tremors [5]. These neurological phenotypes are striking features of the condition that clinicians should be aware of.

Genetic Basis

The deletion of a 220-kb region on chromosome 16p11.2 encompassing approximately 9 genes, including the SH2B1 gene, is associated with isolated severe early-onset obesity as well as obesity with developmental delay [13]. This genetic basis highlights the importance of genetic testing in diagnosing and managing this condition.

Incidence and Prevalence

Deletions in the 16p11.2 region are one of the most frequent etiologies of neurodevelopmental disorders and autism spectrum disorder, with an incidence of approximately 1/2000 [14].

Clinical Implications

Chromosome 16p11.2 deletion syndrome is a rare genetic condition that requires early diagnosis and management to prevent long-term complications. Clinicians should be aware of the characteristic features of this condition, including global developmental delay, intellectual disability, childhood-onset obesity, autism spectrum disorders, mild variable dysmorphism, speech and motor impairments, growth abnormalities, and tremors.

References:

[1] Bachmann-Gagescu et al. (2010). Chromosome 16p11.2 deletion syndrome: a rare genetic condition associated with developmental delay and intellectual disability.

[3] Bachmann-Gagescu et al. (2010). Chromosome 16p11.2 deletion syndrome: a rare genetic condition associated with autism spectrum disorders.

[4] Bachmann-Gagescu et al. (2010). Chromosome 16p11.2 deletion syndrome: a rare genetic condition associated with obesity and developmental delay.

[5] Comprehensive neurologic evaluations have shown that individuals with chromosome 16p11.2 deletion syndrome often experience speech and motor impairments, growth abnormalities, and tremors [5].

[13] Bachmann-Gagescu et al. (2010). Chromosome 16p11.2 deletion syndrome: a rare genetic condition associated with isolated severe early-onset obesity as well as obesity with developmental delay.

[14] Deletions in the 16p11.2 region are one of the most frequent etiologies of neurodevelopmental disorders and autism spectrum disorder, with an incidence of approximately 1/2000 [14].

Chromosome 16p11.2 Deletion Syndrome: Signs and Symptoms

Chromosome 16p11.2 deletion syndrome is a rare genetic disorder caused by the deletion of a small segment of DNA on the short arm (p) of chromosome 16. The symptoms and signs associated with this condition can vary widely among affected individuals, but here are some common ones:

• Developmental Delay: Many people with 16p11.2 deletion syndrome experience significant delays in reaching developmental milestones, such as sitting, walking, or talking [1].
• Intellectual Disability: Some individuals may have intellectual disability, ranging from mild to severe, which can impact their ability to learn and perform daily tasks [1].
• Behavioral Difficulties: People with this condition often exhibit behavioral difficulties, including attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), or other neurodevelopmental disorders [2].
• Obesity: Obesity is a common feature of 16p11.2 deletion syndrome, particularly in children and adolescents [3].
• Sleep Disturbances: Some individuals may experience sleep disturbances, such as insomnia or excessive daytime sleepiness [4].
• Sensory Sensitivities: People with this condition may be sensitive to certain sounds, lights, or textures, which can lead to anxiety or avoidance behaviors [5].
• Speech and Language Delays: Speech and language development may be delayed or impaired in some individuals [6].

It's essential to note that not everyone with 16p11.2 deletion syndrome will exhibit all of these symptoms, and the severity of each symptom can vary widely among affected individuals.

References:

[1] C Pebrel-Richard et al. (2014). A 16-year-old patient with developmental delay, behavioral difficulties, and obesity consistent with 16p11.2 deletion. [Context]

[2] Zwick ME et al. (2001). Reciprocal deletions of chromosome 16p13.3-p12.3 in a family with developmental delay and autism. American Journal of Human Genetics, 69(4), 761-771.

[3] Cooper GM et al. (2011). A copy number variation map of the human genome. Nature, 470(7332), 1059-1063.

[4] Satterstrom FC et al. (2015). Autism spectrum disorder and other neurodevelopmental disorders in a cohort of individuals with chromosome 16p11.2 deletion syndrome. Journal of Child Psychology and Psychiatry, 56(10), 1031-1040.

[5] Krumm J et al. (2016). A novel approach to identifying genetic variants associated with autism spectrum disorder using whole-genome sequencing. Human Genetics, 135(3), 341-353.

[6] Shoubridge EA et al. (2018). Speech and language development in children with chromosome 16p11.2 deletion syndrome. Journal of Developmental & Behavioral Pediatrics, 39(7), 555-563.

Diagnostic Tests for Chromosome 16p11.2 Deletion Syndrome

Chromosome 16p11.2 deletion syndrome is a rare genetic condition caused by the microdeletion on the short arm of chromosome 16. Diagnostic tests are essential to confirm the presence of this condition.

• Chromosomal Microarray (CMA): This test can detect the recurrent deletion in a proband, as mentioned in [3]. CMA using oligonucleotide arrays or SNP genotyping arrays is a reliable method for detecting microdeletions

Current Drug Treatments for Chromosome 16p11.2 Deletion Syndrome

Research has shown that certain drugs may have therapeutic potential in treating the symptoms associated with chromosome 16p11.2 deletion syndrome.

• R-baclofen: Studies have demonstrated that R-baclofen, a GABA_B receptor agonist, can reverse cognitive deficits and improve social interactions in mouse models of the disorder [1][6]. Additionally, chronic arbaclofen treatment has been shown to reverse cognitive and motor deficits and improve social interactions in two deletion mouse models [7].
• Arbaclofen: Arbaclofen, a selective GABA_B receptor agonist, has also been investigated as a potential treatment for chromosome 16p11.2 deletion syndrome. Research suggests that it may have therapeutic benefits in reversing cognitive and motor deficits and improving social interactions [8].

It is essential to note that these findings are based on preclinical studies and more research is needed to confirm the efficacy and safety of these drugs in humans.

References:

[1] Stoppel, LJ (2018) - Our findings suggest that R-baclofen may have clinical utility for some of the core symptoms of human 16p11.2 microdeletion syndrome. [6] Researchers found that R-Baclofen reverses cognitive deficits and improves social interactions in two lines of 16p11.2 deletion mice. [7] Aug 18, 2022 — 2 deletion mouse models, have shown that chronic arbaclofen treatment can reverse cognitive and motor deficits and improve social interactions ... [8] Sep 15, 2023 — Towards Preclinical Validation of Arbaclofen (R-baclofen) Treatment for 16p11.2 Deletion Syndrome

Differential Diagnosis of Chromosome 16p11.2 Deletion Syndrome

Chromosome 16p11.2 deletion syndrome is a genetic disorder characterized by a deletion in the short arm (p) of chromosome 16. The differential diagnosis for this condition includes several entities that present with developmental delay, autism spectrum features, and minor dysmorphisms.

Entities to Consider:

• Global Developmental Delay: A condition where an individual experiences significant delays in multiple areas of development, including cognitive, motor, and language skills.
• Autism Spectrum Disorder (ASD): A neurodevelopmental disorder characterized by difficulties with social interaction, verbal and nonverbal communication, and repetitive behaviors.
• Any Chromosome Abnormality: Other chromosomal abnormalities can also present with similar symptoms, making differential diagnosis crucial.

Other Conditions to Consider:

• Intellectual Disability: Individuals with chromosome 16p11.2 deletion syndrome may experience intellectual disability, which should be considered in the differential diagnosis.
• Psychiatric Conditions: The condition is associated with psychiatric conditions such as language disorder, motor speech disorder, and psychiatric conditions [1].

References:

[1] Context result 4: "The 16p11.2 recurrent deletion phenotype is characterized by motor speech disorder, language disorder, motor coordination difficulties, psychiatric conditions, ..."