Phelan-McDermid Syndrome: Symptoms, Causes, Treatment

What are the symptoms of Phelan-McDermid syndrome?

Phelan-McDermid syndrome is a rare genetic disorder caused by a deletion or mutation of the SHANK3 gene located on chromosome 22. The symptoms of Phelan-McDermid syndrome can vary widely but typically include a range of developmental, physical, and behavioral features. Common symptoms include:

1. Developmental Delays:

• Motor Delays:
• Delayed milestones in motor development, such as sitting, crawling, and walking.
• Speech and Language Delays:
• Significant delays in speech development or the absence of spoken language.

2. Intellectual Disabilities:

• Cognitive Impairments:
• Varying degrees of intellectual disability, from mild to severe.

3. Behavioral and Psychological Symptoms:

• Autistic Traits:
• Features commonly associated with autism spectrum disorders, such as social difficulties, repetitive behaviors, and limited interests.
• Hyperactivity or Attention Issues:
• Problems with attention, hyperactivity, and impulsive behavior.
• Aggression or Self-Injurious Behavior:
• Some individuals may exhibit aggressive behavior or engage in self-injurious actions.

4. Physical Features:

• Distinctive Facial Features:
• Characteristics such as a broad forehead, long face, and a prominent nose may be present, although they can vary.
• Hypotonia:
• Reduced muscle tone or weakness, which can affect motor skills and coordination.

5. Health Concerns:

• Feeding and Gastrointestinal Issues:
• Difficulties with feeding, swallowing, or gastrointestinal problems such as reflux.
• Seizures:
• Seizure disorders may be present in some individuals.

6. Sensory Issues:

• Sensory Processing Difficulties:
• Sensitivities to sensory stimuli or unusual sensory responses.

7. Social and Emotional Challenges:

• Social Interaction Difficulties:
• Challenges in understanding social cues and forming relationships.

Summary:

Phelan-McDermid syndrome presents with a combination of developmental delays, intellectual disabilities, behavioral issues, and sometimes distinct physical features. The severity and range of symptoms can vary greatly among individuals. Early diagnosis and intervention can help manage the symptoms and support development.

What are the causes of Phelan-McDermid syndrome?

Phelan-McDermid syndrome is caused by genetic changes involving the SHANK3 gene on chromosome 22. The primary causes include:

1. Chromosomal Deletions:

• 22q13.3 Deletion:
• The most common cause of Phelan-McDermid syndrome is a deletion of a portion of chromosome 22 at the 22q13.3 region, which includes the SHANK3 gene. The size of the deletion can vary, and larger deletions typically result in more severe symptoms.

2. Genetic Mutations:

• SHANK3 Gene Mutations:
• Mutations or disruptions in the SHANK3 gene, which is crucial for the development and functioning of synapses in the brain, can also cause the syndrome. These mutations may include point mutations, small deletions, or insertions within the SHANK3 gene.

3. Chromosomal Rearrangements:

• Other Chromosomal Changes:
• In rare cases, other types of chromosomal rearrangements involving chromosome 22 or the SHANK3 gene can be implicated.

4. Inherited vs. De Novo Mutations:

• De Novo Mutations:
• Most cases of Phelan-McDermid syndrome are caused by new (de novo) genetic changes that occur spontaneously and are not inherited from the parents.
• Inherited Mutations:
• In some instances, the genetic changes may be inherited from a parent who carries a balanced chromosomal rearrangement or an asymptomatic mutation.

5. Epigenetic Factors:

• Gene Expression Regulation:
• While less common, changes in the regulation of gene expression through epigenetic mechanisms may also contribute to the development of Phelan-McDermid syndrome.

Summary:

Phelan-McDermid syndrome is primarily caused by deletions or mutations affecting the SHANK3 gene on chromosome 22. These genetic changes can disrupt normal brain development and function, leading to the range of symptoms associated with the syndrome. Most cases arise from de novo mutations, but inherited genetic factors can also play a role. Genetic testing is often used to identify the specific genetic cause of the syndrome.

How is the diagnosis of Phelan-McDermid syndrome made?

Diagnosing Phelan-McDermid syndrome involves a combination of clinical evaluation, genetic testing, and sometimes imaging studies. Here’s a step-by-step overview of the diagnostic process:

1. Clinical Evaluation:

• Medical History:
• The healthcare provider will gather detailed information about the patient’s developmental milestones, medical history, and any symptoms that may suggest Phelan-McDermid syndrome.
• Physical and Developmental Examination:
• A thorough physical examination is performed to identify characteristic features of the syndrome, such as developmental delays, intellectual disabilities, and distinct physical features.

2. Genetic Testing:

• Chromosomal Microarray (CMA):
• Primary Test: A chromosomal microarray is often the first test used to detect deletions or duplications of chromosome 22, specifically at the 22q13.3 region where the SHANK3 gene is located. This test can identify the most common genetic abnormalities associated with Phelan-McDermid syndrome.
• SHANK3 Gene Sequencing:
• If chromosomal microarray does not detect abnormalities, sequencing of the SHANK3 gene may be performed to identify mutations or small genetic changes in the gene.
• Karyotyping:
• Supplementary Test: Traditional karyotyping can be used to detect larger chromosomal abnormalities or structural changes that might not be detected by microarray analysis.

3. Imaging Studies:

• Brain Imaging:
• MRI or CT Scan: Imaging studies may be used to assess brain structure and rule out other neurological conditions or abnormalities that could contribute to the symptoms.

4. Genetic Counseling:

• Genetic Counseling:
• Genetic counseling is often provided to help families understand the results of genetic tests, the implications for the individual and family, and options for future management and support.

5. Referral to Specialists:

• Specialist Evaluation:
• Referral to specialists such as a geneticist, neurologist, or developmental pediatrician may be necessary for comprehensive assessment and management.

Summary:

Diagnosing Phelan-McDermid syndrome involves a combination of clinical evaluation to identify characteristic symptoms and genetic testing to confirm the presence of deletions or mutations in the SHANK3 gene. Chromosomal microarray is typically the primary test used, with additional genetic sequencing or karyotyping as needed. Imaging studies and genetic counseling may also be part of the diagnostic process to provide a complete assessment and guide management.

What is the treatment for Phelan-McDermid syndrome?

There is no cure for Phelan-McDermid syndrome, but treatment focuses on managing symptoms and improving quality of life. A multidisciplinary approach is often used, involving various healthcare professionals. Here are some key aspects of the treatment and management for Phelan-McDermid syndrome:

1. Early Intervention:

• Developmental Therapy:
• Physical Therapy: To address motor delays and improve coordination and strength.
• Occupational Therapy: To help with daily living skills, fine motor skills, and sensory processing issues.
• Speech Therapy: To support language development and communication skills.

2. Educational and Behavioral Support:

• Special Education Services:
• Tailored educational plans and support in school settings to address learning difficulties and developmental delays.
• Behavioral Therapy:
• Techniques to manage behavioral challenges, including social skills training and strategies for managing autism spectrum disorder traits.

3. Medical Management:

• Medication:
• Seizure Management: If seizures are present, anticonvulsant medications may be prescribed.
• Psychiatric Medications: Medications may be used to manage associated behavioral issues or mood disorders, such as anxiety or ADHD.
• Regular Medical Check-Ups:
• Routine evaluations to monitor health issues, developmental progress, and any additional conditions.

4. Support Services:

• Genetic Counseling:
• To provide information about the condition, inheritance patterns, and family planning options.
• Support Groups:
• Connection with support groups or organizations for families affected by Phelan-McDermid syndrome can provide resources, shared experiences, and emotional support.

5. Addressing Specific Symptoms:

• Gastrointestinal Issues:
• Management of feeding difficulties or gastrointestinal problems, possibly including dietary modifications or medications.
• Sensory Processing Issues:
• Strategies to address sensory sensitivities or difficulties, often involving occupational therapy.

6. Research and Clinical Trials:

• Participation in Research:
• Families may consider participation in clinical trials or research studies aimed at finding new treatments or understanding the syndrome better.

7. Multidisciplinary Team:

• Coordination of Care:
• Collaboration between various specialists, including pediatricians, neurologists, geneticists, and therapists, to provide comprehensive care and support.

Summary:

Treatment for Phelan-McDermid syndrome is individualized and focuses on managing symptoms and improving functional abilities. Early intervention, educational support, medical management, and addressing specific needs are crucial components of the care plan. A multidisciplinary approach and support services play key roles in enhancing quality of life and providing support for affected individuals and their families.