Clinical Condition

Introduction

PURA Syndrome is a rare neurodevelopmental disorder caused by mutations in the PURA gene, leading to a range of symptoms including developmental delay, intellectual disability, and hypotonia. Diagnosis is based on clinical features and genetic testing. Management involves a multidisciplinary approach with interventions tailored to the individual's needs, including speech and language therapy, occupational therapy, and assistive technologies. Ongoing research aims to improve understanding and treatment of the disorder.

Demographic Information

• Incidence: Rare, exact incidence unknown
• Prevalence: Fewer than 100 cases reported in the medical literature to date
• Gender: Affects both males and females equally
• Onset Age: Symptoms present from birth or early infancy

Coding

• ICD-11: 6A00.2Y
• OMIM: 616158
• UMLS: C4021816
• MeSH: Not yet assigned
• GARD: 26987

Medical Features and Pathophysiology

Etiology

PURA Syndrome is caused by mutations in the PURA gene, which plays a critical role in brain development and function. The exact mechanism by which these mutations cause the symptoms of PURA Syndrome is still being researched, but it involves disruptions in neuronal development and function.

Pathology

The PURA gene encodes Pur-alpha, a protein involved in DNA and RNA binding, which is crucial for the regulation of gene expression and the development of the nervous system. Mutations in the PURA gene lead to impaired function of this protein, resulting in a spectrum of neurodevelopmental issues, including developmental delay, intellectual disability, and hypotonia (low muscle tone).

Symptoms

Neurodevelopmental

• Global developmental delay
• Intellectual disability
• Speech and language impairment

Neurological

• Hypotonia (low muscle tone)
• Epilepsy or seizure activity
• Feeding difficulties

Other Symptoms

• Respiratory issues
• Hypothermia (especially in infancy)
• Sleep disturbances

Diagnosis

Diagnosis of PURA Syndrome is based on clinical features and confirmed through genetic testing:

• Genetic Testing: Identification of mutations in the PURA gene through whole exome sequencing or targeted genetic panels.
• Clinical Evaluation: Assessment of developmental milestones, neurological examination, and evaluation of associated symptoms.

Assistive Suggestions and Requirements

Requirement Percentage for Assistive Technology

Most patients with PURA Syndrome will benefit from assistive technology to support communication, mobility, and daily living activities.

Assistive Technology Suggestions

• Communication Aids:

- Speech Generating Devices (SGDs): For individuals with significant speech impairments.

• Mobility Aids:

- Adaptive Seating: To provide support and stability.

• Feeding Aids:

- Gastrostomy Tubes (G-tubes): For severe feeding issues.

• Environmental Control:

Access Modalities

• Touchscreen Devices: Suitable for children with good hand function.
• Switch Access: For those with more severe motor impairments.
• Eye-Gaze Technology: For individuals with significant motor and communication difficulties.

Care Management and Therapeutic Techniques

Aims

• To manage symptoms and support the child’s developmental potential.
• To provide multidisciplinary care and support to the family.
• To enhance quality of life through personalized interventions and assistive technologies.

SLP Suggestions

• Assessment and Intervention:

- Communication Strategies: Introducing AAC devices early to facilitate communication. - Language Therapy: Focusing on functional communication skills.

• Augmentative and Alternative Communication (AAC):

Special Educator Suggestions

• Individualized Education Plan (IEP):

- Goals focusing on communication, cognitive skills, and social interactions.

• Behavioral Strategies:

- Implementation of sensory-friendly classroom environments.

Occupational Therapist Suggestions

• Daily Living Skills:

- Techniques to improve fine motor skills and independence.

• Sensory Integration Therapy:

- Creation of sensory-friendly environments to reduce overstimulation.

Recommendations on AAC and Other Details

• Text-Based AAC:

• Symbol-Based AAC:

References

1. Hunt, D., Leventer, R. J., Simons, C., Taft, R., & Farrow, E. (2014). Gained and Lost Domains of Function in the Spectrum of Mutations in the PURA Gene. Journal of Molecular Neuroscience, 54(4), 418-426. 2. Lalani, S. R., Zhang, J., Schaaf, C. P., Brown, C. W., Magoulas, P., Tsai, A. C., ... & Yang, Y. (2014). Mutations in PURA cause profound neonatal hypotonia, seizures, and encephalopathy. American Journal of Medical Genetics Part A, 164A(4), 1400-1405. 3. Reijnders, M. R., Janowski, R., Alvi, M., Self, J. E., van Essen, T. J., Vreeburg, M., ... & Elting, M. W. (2018). PURA syndrome: clinical delineation and genotype-phenotype study in 32 individuals with review of published literature. Journal of Medical Genetics, 55(2), 104-113.

Additional Information

PURA Syndrome is a rare genetic disorder requiring a comprehensive and multidisciplinary approach to management. Regular follow-ups with a team of healthcare professionals, including neurologists, geneticists, speech-language pathologists, occupational therapists, and special educators, are essential. Education and support for patients and caregivers, along with access to community resources and support groups, can provide valuable assistance in managing this complex condition.

Extended Information

Pathological Insights and Disease Mechanism

PURA Syndrome is caused by mutations in the PURA gene, which encodes the Pur-alpha protein. This protein plays a crucial role in regulating gene expression and maintaining neuronal function. The mutations disrupt normal cellular processes, leading to the broad spectrum of neurological and developmental symptoms seen in affected individuals.

Genetic and Environmental Factors

PURA Syndrome follows an autosomal dominant inheritance pattern, meaning a single copy of the mutated gene can cause the disorder. Most cases are de novo mutations, occurring spontaneously rather than being inherited from a parent. Genetic counseling is recommended for families to understand the risks and implications of the disorder.

Clinical Presentation and Disease Progression

Symptoms of PURA Syndrome are present from birth or early infancy, with affected individuals displaying significant developmental delays, hypotonia, and intellectual disability. The severity of symptoms can vary widely, but most individuals will require lifelong support and interventions to manage their condition.

Differential Diagnosis and Overlapping Syndromes

Diagnosing PURA Syndrome involves distinguishing it from other neurodevelopmental disorders that present with similar symptoms, such as Rett syndrome, Angelman syndrome, and other genetic conditions. Genetic testing is essential to confirm the diagnosis and guide management.

Therapeutic Interventions and Symptom Management

Management of PURA Syndrome involves a combination of therapies and interventions tailored to the individual's needs. Early intervention with speech and language therapy, occupational therapy, and physical therapy is crucial. Seizures and other medical issues require ongoing medical management. Assistive technologies play a significant role in supporting communication and daily living activities.

Research and Future Directions

Research into PURA Syndrome is ongoing, with efforts focused on understanding the underlying mechanisms, identifying potential therapeutic targets, and improving diagnostic criteria. Advances in genetic research and neurobiology hold promise for developing new treatments and improving outcomes for individuals with PURA Syndrome.

Support and Resources

Organizations such as the PURA Syndrome Foundation provide resources, support networks, and advocacy for individuals affected by PURA Syndrome. These organizations offer educational materials, connect families with healthcare professionals, and support research initiatives aimed at improving understanding and treatment of the disorder. Support groups and online communities provide valuable emotional support and practical advice for parents and caregivers.

In conclusion, PURA Syndrome is a rare and complex neurodevelopmental disorder requiring comprehensive management and multidisciplinary care. Early diagnosis, tailored interventions, and ongoing support are essential for improving the quality of life for affected individuals and their families. Advances in research offer hope for future improvements in understanding and treating this challenging condition.

Epidemiology and Demographics

Etiology and Pathophysiology

Clinical Features and Stages

Diagnosis

Clinical Recommendations

Care Management

Transition Planning