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Clinical Resources

Evidence-based screening protocols and clinical guides grounded in systematic literature review. Tools you can use with patients today.

Quick Access

Screening Protocols

When, what, and how to screen

22q11.2DS Guide

Complete clinical management

Referral Criteria

When to refer to specialists

Patient Materials

Handouts and education

Key Clinical Points

22q11.2DS Autoimmunity

Moderate
  • 23-31% develop autoimmune disease
  • 50-80× elevated lupus risk
  • Same thymic defect causes BOTH deficiency AND autoimmunity
  • Screening from age 5 can catch disease early

22q11.2DS Psychosis

High
  • 25× elevated schizophrenia risk
  • Peak onset: adolescence and early adulthood
  • Prodromal symptoms may be identifiable
  • Annual psychiatric screening recommended

Screening Protocols

22q11.2DS Autoimmune Screening

Who: All 22q11.2DS patients, regardless of current symptoms

When: Begin at age 5, then annually

Annual Screening Protocol
Test Frequency Action if Abnormal
ANA Annual from age 5 If positive: check ENA, anti-dsDNA, complements
TSH Annual If abnormal: check Free T4, thyroid antibodies
CBC Annual Evaluate for cytopenias
Urinalysis Annual Evaluate for proteinuria

High-Risk Patients (Enhanced Screening)

Monitor every 6 months if:

  • ANA positive
  • Any autoantibody positive
  • Low CD4 count (<500/μL)
  • Family history of autoimmunity
  • Previous autoimmune symptoms

Lupus Screening Decision Tree

ANA Screening Protocol

Baseline (age 5+):
├── ANA
│
├── If ANA negative → Annual ANA
│
└── If ANA positive (≥1:80)
    ├── Check: anti-dsDNA, anti-Sm, anti-RNP, C3, C4
    │
    ├── If all negative → Repeat in 6 months
    │
    └── If ANY positive → Rheumatology referral
        └── Consider hydroxychloroquine

GI Screening Protocol

Based on TLR9 pathway convergence between 22q, lupus, and IBD:

Rationale

The same innate immune pathways (TLR9) implicated in 22q-lupus risk are also involved in IBD. While 22q-IBD epidemiology is not yet established, biological reasoning supports screening.

  • All 22q patients: Annual GI symptom review
  • If symptoms: Consider fecal calprotectin
  • High-risk (ANA+, autoimmune history): Enhanced 6-month surveillance
Full GI Screening Protocol IBD-Lupus Convergence Research

22q11.2DS Clinical Management Guide

The Immune Paradox

22q11.2DS patients have both:

  • Immune deficiency: More infections due to T-cell deficiency
  • Autoimmunity: Self-attack due to tolerance defects

This paradox is explained by thymic hypoplasia: fewer T cells overall (deficiency) + impaired negative selection allowing self-reactive cells to escape (autoimmunity).

Autoimmune Diseases in 22q11.2DS

Condition Prevalence in 22q vs. General Pop.
Systemic lupus erythematosus 3-5% 50-80× elevated
Thyroid autoimmunity 10-20% 5-10× elevated
Idiopathic thrombocytopenia 5-10% 500× elevated
Juvenile idiopathic arthritis 3-5% 20-30× elevated
Hemolytic anemia 2-5% ~1000× elevated

Hydroxychloroquine in 22q11.2DS

HCQ Mechanism

HCQ inhibits TLR9, the convergent pathway for autoimmunity in 22q11.2DS:

  • Blocks self-DNA recognition
  • Reduces Type I interferon
  • Prevents B-cell activation

HCQ Indications

Established: SLE (any severity), Discoid lupus, Antiphospholipid syndrome

Consider: Seropositive but clinically quiescent, High-risk with multiple autoantibodies

HCQ Monitoring

  • Baseline ophthalmologic exam
  • Annual eye exam after 5 years
  • CBC, LFTs annually
  • Generally very well tolerated

Referral Criteria

Rheumatology Referral

  • Positive ANA with any other autoantibody
  • Unexplained rash (especially malar/butterfly)
  • Joint pain or swelling
  • Oral ulcers
  • Unexplained fatigue
  • Hair loss
  • Proteinuria
  • Low complements (C3, C4)

Other Specialist Referrals

Endocrinology:

  • Abnormal TSH
  • Symptoms of hypo/hyperthyroidism
  • Positive thyroid antibodies

Hematology:

  • Unexplained anemia or thrombocytopenia
  • Signs of hemolysis

Nephrology:

  • Proteinuria, elevated creatinine, hypertension

Patient Education Materials

Key Points for Patients and Families

  1. Autoimmunity is common in 22q — Not something to be alarmed about, but to monitor
  2. Symptoms matter — Report new symptoms like rash, joint pain, fatigue, weight changes
  3. Screening saves problems — Annual tests catch issues early
  4. Treatment works — Autoimmune conditions are very manageable when caught early
  5. Coordination is key — Keep all your doctors informed about 22q

When to Seek Care

Call Your Doctor
  • New or worsening fatigue
  • Unexplained rash
  • Joint pain or swelling
  • Unusual bruising or bleeding
  • Hair loss
Go to Emergency Room
  • Severe headache with fever
  • Difficulty breathing
  • Chest pain
  • Seizure
  • Confusion

Downloadable Materials

Patient Screening Card
Wallet card with screening schedule
Symptom Checklist
For patients to track symptoms
Care Coordination Sheet
For multi-specialty communication

Coordination of Care

Specialist Role
Primary care Coordination, routine screening
Genetics Diagnosis, family counseling
Immunology Immune deficiency management
Rheumatology Autoimmune disease
Endocrinology Thyroid, calcium
Psychiatry Mental health screening, treatment
Communication Best Practice

Ensure all providers know about the 22q diagnosis. Share screening results across the team. Designate a care coordinator (usually primary care).

Evidence-Based, Validation-Pending

These protocols are grounded in systematic literature review and current best evidence. However, no RCTs have been conducted specifically in 22q11.2DS populations for many interventions. Clinical judgment must guide individual patient care.

View Supporting Evidence