Monosomy 22q13

1. Disease Summary:

Monosomy 22q13, also known as Phelan-McDermid syndrome (PMS), is a neurodevelopmental disorder caused by a deletion in the 22q13.3 region of chromosome 22 or a pathogenic variant of the SHANK3 gene. The syndrome is characterized by a range of symptoms including global developmental delay, intellectual disability, severe speech impairment, hypotonia, and various psychiatric and somatic comorbidities. Individuals with PMS often face significant challenges in communication, social interaction, and daily living skills, which profoundly affect their quality of life and that of their families.

2. Global Prevalence and Disease Burden:

The prevalence of Phelan-McDermid syndrome is estimated to be between 0.5% and 2.0% of cases of autism spectrum disorder (ASD) and intellectual disability, with at least 1,200 cases reported worldwide (Costales JL, Kolevzon A, 2015, PMID: 25894671). The disease burden is substantial, as individuals with PMS often require lifelong support and care, leading to significant economic impacts on families and healthcare systems. The costs associated with managing PMS include medical care, therapy services, and support for caregivers, which can be overwhelming for families.

3. Unmet Medical Need:

Despite the recognition of Phelan-McDermid syndrome, there are several unmet medical needs that significantly impact the lives of affected individuals and their families:

Mental Health Support: Caregivers report a lack of adequate mental health resources for individuals with PMS. The variability in developmental levels and the presence of psychiatric comorbidities necessitate tailored mental health interventions (van Balkom IDC et al., 2023, PMID: 37085014). Current mental health care often does not address the unique challenges faced by individuals with PMS, leading to unmet needs in this area.
Communication and Cognitive Function: Caregivers prioritize improvements in communication abilities and cognitive function for their loved ones. The inability to communicate effectively is a significant concern, as it affects social interactions and independence (Gizzo L et al., 2024, PMID: 38532502). There are currently no specific therapies targeting these areas.
Sleep Disorders: Sleep problems are prevalent in individuals with PMS, affecting up to 90% of patients. These issues can exacerbate behavioral problems and impact the well-being of caregivers (San Jose Caceres A et al., 2023, PMID: 36963463). There is a lack of PMS-specific treatments for sleep disorders, and existing recommendations are based on general guidelines for intellectual disabilities.
Gastrointestinal Issues: Many individuals with PMS experience gastrointestinal symptoms, which can complicate their overall health and quality of life. However, there is limited research on effective management strategies for these symptoms (Halladay A et al., 2024, PMID: 39257288).

4. Current Treatment Options:

Currently, treatment options for Phelan-McDermid syndrome are largely supportive and symptomatic, focusing on managing individual symptoms rather than addressing the underlying genetic cause. These include:

Therapies: Speech therapy, occupational therapy, and physical therapy are commonly employed to help improve communication skills, motor function, and daily living skills. However, these therapies do not specifically target the genetic basis of PMS and may not be effective for all individuals.
Medications: Medications may be prescribed to manage specific symptoms such as anxiety, attention deficits, or sleep disturbances. However, there are no medications specifically approved for PMS, and the effectiveness of these treatments can vary widely among individuals.
Support Services: Caregiver support groups and educational resources are available through organizations like the Phelan-McDermid Syndrome Foundation. These resources aim to provide information and emotional support to families, but they do not address the clinical needs of patients directly.

5. Current Clinical Trials:

There are ongoing clinical trials exploring novel therapeutic approaches targeting the SHANK3 pathway, which is implicated in PMS. These trials aim to develop treatments that could potentially improve cognitive function and communication abilities in affected individuals. However, specific details on the status and outcomes of these trials are still emerging.

6. Additional Context:

The economic impact of Phelan-McDermid syndrome is significant, as families often face high costs associated with medical care, therapies, and support services. The burden of caregiving can also lead to mental health challenges for caregivers, further complicating the overall care landscape. Advocacy efforts are crucial in raising awareness and pushing for research into effective treatments that address the unmet needs of individuals with PMS.