Anxiety disorder is a common psychopathological comorbidity in patients with SHANK pathogenic variants: description of five new cases - Scorecard - MDSpire
Advertisement
Anxiety disorder is a common psychopathological comorbidity in patients with SHANK pathogenic variants: description of five new cases
Clinical Scorecard: Prevalence of Anxiety Disorders in Patients with SHANK Gene Variants: A Report on Five New Cases
At a Glance
Category
Detail
Condition
Neurodevelopmental disorders with psychiatric comorbidity linked to SHANK gene variants
Key Mechanisms
Pathogenic variants in SHANK1, SHANK2, SHANK3 genes affecting synaptic scaffold proteins at glutamatergic synapses
Target Population
Children and adolescents aged 6–18 years with mild intellectual disability (MID) or borderline intellectual functioning (BIF) and psychiatric comorbidity
Care Setting
Child Mental Health Centre at a tertiary hospital (Parc Taulí Hospital Universitari, Catalunya, Spain)
Key Highlights
SHANK gene variants are implicated in neurodevelopmental disorders including autism spectrum disorder (ASD), intellectual disability, and psychiatric comorbidities such as anxiety.
Whole exome sequencing enables identification of pathogenic single nucleotide variants in SHANK genes, with SHANK3 variants linked to Phelan-McDermid syndrome and other neuropsychiatric phenotypes.
Five new patients with pathogenic SHANK1, SHANK2, and SHANK3 variants were identified, representing 4.3% of a cohort with MID/BIF and psychiatric comorbidity.
Guideline-Based Recommendations
Diagnosis
Use whole exome sequencing for genetic diagnosis in patients with MID/BIF and psychiatric comorbidities.
Confirm candidate variants by Sanger sequencing and classify according to ACMG/AMP guidelines.
Conduct comprehensive neuropsychiatric evaluation using DSM-5 criteria and validated clinical scales (e.g., WISC-V/WAIS, Conners Scale, CBCL, CDI, STAIC).
Management
Multidisciplinary care involving child psychiatry and psychology specialists.
Consider genetic counseling for families of patients with identified SHANK variants.
Tailor interventions to address neurodevelopmental and psychiatric symptoms, including anxiety disorders.
Monitoring & Follow-up
Regular neuropsychiatric assessments to monitor symptom progression and treatment response.
Evaluate functional status using validated scales such as the Honosca scale.
Monitor for emergence or changes in psychiatric comorbidities over time.
Risks
Increased risk of autism spectrum disorder, intellectual disability, speech and motor delays associated with SHANK variants.
Potential for neuropsychiatric disturbances including anxiety disorders and other psychiatric comorbidities.
Genetic heterogeneity requires careful interpretation of variant pathogenicity.
Patient & Prescribing Data
Children and adolescents with MID/BIF and psychiatric comorbidity harboring SHANK gene variants
Pharmacological treatment data were collected but specific prescribing patterns or efficacy outcomes are not detailed in the source material.
Clinical Best Practices
Obtain informed consent and ethical approval for genetic testing and clinical evaluations.
Use standardized and validated neuropsychological and psychiatric assessment tools administered by trained specialists.
Integrate genetic findings with clinical phenotyping to guide diagnosis and management.
Document dysmorphological features using Human Phenotype Ontology terms for comprehensive phenotyping.
Submit identified variants to public databases such as ClinVar to support variant interpretation.
Background music and multimedia exposure were associated with lower patient-reported anxiety in a quasi-experimental ophthalmology clinic study that used existing clinic audiovisual infrastructure at no additional cost.
