---
id: rd_clinical_report_format
name: Clinical Genetics Report Format
description: |
  Authoritative format contract for the rare disease final report: cover page,
  4-level numbering, 9 sections, sign-off, machine-readable JSON, and the
  standalone HTML clinical theme (embedded CSS + weasyprint PDF path).
tags: [rare_disease, clinical_report, html_theme, format_contract]
---

# Clinical Genetics Report Format Contract

The final deliverable is a **formal clinical genetics consult report** — not a
chat message, not a memo. This file defines its exact structure and theme.
Follow it precisely: do not flatten numbering, drop sections, or improvise CSS.

## Output Language

- Produce the report in **the same language as the user's input**.
- Chinese input → entire body (section titles, table headers, narrative) in Chinese.
- English input → output in English.
- Disease names, gene symbols, HPO IDs, OMIM/ORPHA IDs always remain in their
  original English form regardless of output language.

---

## Numbering System

Use this exact 4-level hierarchy. **Do not flatten or re-order.**

English:
```
1. {Section Title}
  1.1 {Sub-section Title}
    1.1.1 {Item Title}
      (a) {Sub-item Title}
```

Chinese:
```
一、{章节标题}
  (一){子节标题}
    1.{条目标题}
      (1){子条目标题}
```

Section titles below are given in English as the canonical reference. Translate
each to the output language when producing the report.

---

## Report Structure — Cover Page + 9 Sections

### Cover Page

Begin every report with a cover page containing:

1. **Report Title**: "Rare Disease Differential Diagnosis Support Report"
   (translate to output language)
2. **Metadata Table**:

| Field | Value |
|-------|-------|
| Report ID | RD-{YYYYMMDD}-{case_id} |
| Classification | Internal Reference |
| Patient Age | {age} |
| Patient Sex | {sex} |
| Phenotype Count | {N} |
| Genotype Data | Present / Absent |
| Analysis Mode | Multi-Disciplinary Team (MDT) — Multi-Agent |
| Generation Date | YYYY-MM-DD |
| Framework Version | PantheonOS rare_disease_team |

3. **Analysis Pipeline**:
   Ontology Normalization → Evidence Retrieval → Audit → Report Generation
   (researcher[ontology] → researcher[evidence] → auditor → leader[report])

4. **Institution**: PantheonOS AI Analysis (non-clinical testing facility)

5. **Disclaimer** (verbatim, translated to output language):
   This report is generated by an AI-assisted differential diagnosis system
   for clinical reference only. It does not replace the independent
   professional judgment of a licensed physician. The final diagnosis must
   be determined by a qualified clinician based on complete clinical data,
   physical examination, and necessary ancillary tests.

---

### Section 1: Clinical Information

**1.1 Chief Complaint & History**

Structured clinical narrative. 5–8 lines covering: age, sex, chief complaint,
key findings, developmental history, past medical history, family history.

**1.2 Reason for Referral**

1–2 sentences: why this case warrants rare disease differential analysis.

**1.3 Phenotype Inventory**

| # | Original Description | HPO Term | HPO ID | Status | Notes |
|:-:|---------------------|----------|--------|:------:|-------|
| 1 | {original} | {HPO term} | HP:xxxxxxx | ✓ | {note} |
| 2 | {original} | {HPO term} | HP:xxxxxxx | ? | {note} |

Status: ✓ = confirmed, ? = uncertain, ✗ = explicitly absent (pertinent negative)

---

### Section 2: Primary Candidate Diseases

**2.1 Candidate Overview**

A scannable summary table — clinician reads this in 30 seconds.

| Rank | Disease Name | OMIM/ORPHA | Gene | Inheritance | Support | Key Matches |
|:----:|-------------|------------|------|:-----------:|:------:|-------------|
| 1 | {disease} | OMIM:xxx | GENE | AD/AR/XL | ★★★★☆ | {matches} |
| 2 | {disease} | ORPHA:xxx | GENE | AD | ★★★☆☆ | {matches} |

Stars: ★★★★★ = definitive (genetically confirmed), ★★★★☆ = highly suggestive,
★★★☆☆ = moderately suggestive, ★★☆☆☆ = weak, ★☆☆☆☆ = exploratory.

**2.2 Per-Candidate Detailed Interpretation**

For each candidate in the overview table, produce this exact block:

```
### Candidate {N}: {disease_name} ({OMIM/ORPHA ID})

**Disease Overview**: {1–2 sentence summary — characteristics, epidemiology}

**Gene & Inheritance**: {GENE}, {autosomal dominant / recessive / X-linked / mitochondrial}

#### Phenotype Match Analysis

| Input Phenotype | Match Status | Explanation |
|----------------|:------------:|-------------|
| {phenotype} (HP:xxxxxxx) | ✓ Match | {why} |
| {phenotype} (HP:xxxxxxx) | △ Partial | {may be seen, not classic} |
| {phenotype} | ✗ No Match | {absent in typical presentation} |

#### Evidence Support

| Evidence Type | Content | Source |
|--------------|---------|--------|
| Phenotype Match | {summary} | Clinical observation |
| Literature | {key finding} | PMID: xxxxx |
| Database | {ClinVar / gnomAD / Orphanet info} | {database name} |

#### Counter-Evidence

- {inconsistent or missing finding}
- {inconsistent or missing finding}

#### References

- PMID:{xxxxxxx} — {one-line relevance summary}
- DOI:{xx.xxxx/xxx} — {one-line relevance summary}
```

- Provide up to 5 ranked candidates. Only include candidates with at least
  minimal evidence support (phenotype overlap or database annotation).
- Do not fabricate candidates to fill 5 slots. If fewer than 5 are supported,
  explain the evidence gap in Section 5.2 (Uncertainty Sources).
- Mark genuinely speculative entries as `[Exploratory — insufficient evidence]`
  and place them last.
- Use exact ontology-backed disease names — never collapse to family labels.
- Uncertainty belongs in analysis fields, never in the disease name.

---

### Section 3: Evidence Summary

**3.1 Evidence Strength Overview**

| Candidate | Phenotype Match | Literature | Database | Overall |
|-----------|:--------------:|:----------:|:--------:|:-------:|
| 1. {disease} | Strong | Moderate | Strong | ★★★★☆ |
| 2. {disease} | Moderate | Weak | Moderate | ★★★☆☆ |

**3.2 Key Literature**

| PMID/DOI | Summary | Relevance to Case | Evidence Level |
|----------|---------|-------------------|:--------------:|
| PMID:xxxxx | {one-line} | {why relevant} | A / B / C / D |

Levels: A = systematic review / guideline, B = cohort / case series,
C = single case report, D = database annotation.

---

### Section 4: Missing Information & Follow-Up

| Priority | Missing Information | Clinical Impact | How to Obtain |
|:--------:|--------------------|-----------------|---------------|
| 1 (urgent) | {what} | directly affects top-1 | {method} |
| 2 (high) | {what} | distinguishes cand. 1 vs 2 | {method} |
| 3 (medium) | {what} | rules out candidate 3 | {method} |
| 4 (low) | {what} | supplementary only | history follow-up |

---

### Section 5: Risk & Uncertainty

**5.1 Key Risks**

- {risk}: explicit statement of what could go wrong if misinterpreted.
- {risk}: statement the clinician must NOT misinterpret.

**5.2 Uncertainty Sources**

| Uncertainty | Severity | Impact on Ranking |
|------------|:--------:|-------------------|
| Sparse phenotype input | High | ranking may shift significantly |
| {source} | Medium | {impact} |

---

### Section 6: Recommended Next Steps

| Priority | Test / Investigation | Purpose | Expected Timeline |
|:--------:|---------------------|---------|:-----------------:|
| 1 | {specific test name} | confirm / exclude candidate 1 | 1–2 weeks |
| 2 | {imaging / lab} | distinguish candidate 1 vs 2 | 1 week |
| 3 | {genetic test} | molecular diagnosis | 4–6 weeks |
| 4 | {follow-up / referral} | supplementary information | ongoing |

Specify test types precisely: CMA, trio WES, trio WGS, targeted gene panel,
single-gene sequencing. Include sample requirements and expected turnaround.

---

### Section 7: Conclusions & Recommendations

**7.1 Core Conclusions** — 3–5 sentences, 30-second read

```
1. Most likely diagnostic direction: {top candidate category}
2. Most dangerous alternative to exclude: {alternative}
3. 1–2 highest-yield next steps: {next steps}
4. Current evidence strength: {summary}
5. Suggested phrasing for medical record: {one sentence}
```

**7.2 Differential Diagnosis Conclusion Table**

| Candidate | Current Evidence | Key Differential to Exclude | Suggested Molecular Test |
|-----------|:----------------:|----------------------------|-------------------------|
| 1. {disease} | ★★★★☆ | {differential} | {gene} sequencing |
| 2. {disease} | ★★★☆☆ | {differential} | {panel name} |

---

### Section 8: Technical Notes

**8.1 Methodology Limitations**

1. This analysis is based on phenotype-to-disease ontology matching and does not
   include genomic variant detection (unless genotype data was provided).
2. Ontology sources: Orphanet (latest release), OMIM, HPO (latest release).
3. Rankings are constrained by the completeness of input phenotypes; adding key
   missing phenotypes may significantly alter the ranking.
4. This system was not trained on patient-specific genomic data.
5. AI-generated content may contain hallucinations; all disease-phenotype
   associations have been cross-validated via literature/database retrieval.

**8.2 Glossary**

| Abbreviation | Full Name | Notes |
|-------------|-----------|-------|
| AD | Autosomal Dominant | — |
| AR | Autosomal Recessive | — |
| XL | X-linked | — |
| CHH | Congenital Hypogonadotropic Hypogonadism | — |
| GDD | Global Developmental Delay | — |
| CDGP | Constitutional Delay of Growth and Puberty | — |
| CMA | Chromosomal Microarray | First-tier CNV detection |
| WES | Whole Exome Sequencing | — |
| WGS | Whole Genome Sequencing | — |
| HPO | Human Phenotype Ontology | — |
| OMIM | Online Mendelian Inheritance in Man | — |
| ACMG | American College of Medical Genetics and Genomics | Variant classification |

---

### Section 9: Sign-Off

**签字栏（中文报告）/ Report Sign-Off（英文报告）**

| 角色 / Role | 机构 / Entity | 签名 / Signature | 日期 / Date |
|------------|--------------|-----------------|------------|
| AI 分析员 / AI Analyst | PantheonOS rare_disease_team | (system) | YYYY-MM-DD |
| 审核人 / Reviewer | （待人工填写） | | |
| 批准人 / Approver | （待填写） | | |

**免责声明 / Disclaimer:**

1. 本报告由 AI 辅助鉴别诊断系统生成，仅供临床参考，不替代执业医师的独立专业判断。
   This report is AI-generated for clinical reference only and does not replace
   independent professional judgment of a licensed physician.
2. 疾病排名基于当前表型输入，不构成最终诊断。
   Disease rankings are based on current phenotype input and do not constitute
   a definitive diagnosis.
3. 最终诊断须由具备资质的临床医师结合完整临床评估确定。
   Final diagnosis must be determined by a qualified clinician based on complete
   clinical evaluation.
4. 基因检测建议应在遗传咨询师指导下执行。
   Genetic testing recommendations should be pursued under the guidance of a
   genetic counselor.

---
© {YYYY} PantheonOS. Report ID: RD-{YYYYMMDD}-{case_id}

**每页页脚 / Page footer (every page after cover):**
`RD-{YYYYMMDD}-{case_id}　　　　　　　　　　　　　　　　　　Page {page}/{total}`

---

## Machine-Readable Output (required after Section 9)

> **Field notes for the JSON block:**
> - `blind_safe`: `true` when the report was generated from a de-identified or
>   synthetic case (e.g., benchmark/evaluation runs). `false` for real patient cases.
>   Used by `evaluate_rd_benchmark.py` to filter evaluation results.
> - `clinical_urgency`: `routine` = standard workup timeline; `elevated` = expedite
>   within days; `urgent` = same-day escalation warranted.

```json
{
  "report_metadata": {
    "report_id": "RD-{YYYYMMDD}-{case_id}",
    "generated_at": "{ISO 8601 timestamp}",
    "template_version": "rare_disease_team v0.2.0",
    "model": "{model_name}",
    "workflow_status": "full_team_success",
    "called_agents": ["researcher:ontology", "researcher:evidence", "auditor", "leader:report"],
    "genotype_mode_used": false,
    "language": "{output language}",
    "page_count": N
  },
  "ranked_candidates": [
    {
      "rank": 1,
      "disease": "Exact canonical disease name",
      "disease_uid": "OMIM:xxxxxx",
      "gene": "GENE_SYMBOL",
      "inheritance": "AD|AR|XL|mitochondrial",
      "support_level": "high|moderate|low|exploratory",
      "key_pmids": ["PMID:xxxxx"],
      "key_phenotype_matches": ["HP:xxxxxxx"],
      "key_counter_evidence": "brief text"
    }
  ],
  "hpo_terms_observed": ["HP:xxxxxxx"],
  "hpo_terms_absent": ["HP:xxxxxxx"],
  "evidence_summary": {
    "total_references": N,
    "pmids": ["PMID:xxxxx"],
    "dois": ["10.xxxx/xxx"]
  },
  "clinical_urgency": "routine|elevated|urgent",
  "blind_safe": false
}
```

---

## HTML Output — Clinical Report Theme

Always produce a standalone `.html` file with embedded CSS as the primary
deliverable. PDF is derived from this HTML via `weasyprint` only when requested.

Write the report as `report/RD-{YYYYMMDD}-{case_id}.html`.

### Embedded CSS (inline in `<style>`)

Clean white canvas, teal-navy accents, sans-serif body for clinical readability.
Dense tables, clear hierarchy, print-optimized A4 layout.

```css
:root {
  --white: #ffffff;
  --off-white: #f8fafb;
  --brand: #0f4c75;
  --brand-light: #e8f1f8;
  --accent: #1b6b93;
  --near-black: #1a2332;
  --body-text: #2d3748;
  --stone: #64748b;
  --border: #e2e8f0;
  --border-strong: #cbd5e1;
  --success: #166534;
  --warning: #b45309;
}

body {
  background: var(--white); color: var(--body-text);
  font-family: -apple-system, BlinkMacSystemFont, "Segoe UI", "PingFang SC",
    "Microsoft YaHei", "Noto Sans CJK SC", "Helvetica Neue", Arial, sans-serif;
  font-size: 10.5pt; line-height: 1.6;
  max-width: 780px; margin: 0 auto; padding: 32px 24px;
}

.cover-page {
  text-align: center; padding: 48px 0 32px;
  border-bottom: 2px solid var(--brand); margin-bottom: 32px;
}
.cover-page h1 {
  font-size: 18pt; font-weight: 700; color: var(--brand);
  margin-bottom: 24px; letter-spacing: 0.5pt;
}
.report-id {
  display: inline-block; background: var(--brand); color: var(--white);
  font-size: 9pt; font-weight: 600; padding: 3px 10px;
  border-radius: 3px; margin-bottom: 16px;
}

h1 {
  font-size: 16pt; font-weight: 700; color: var(--brand);
  margin: 32px 0 12px; padding-bottom: 6px;
  border-bottom: 1.5px solid var(--border-strong);
}
h2 {
  font-size: 13pt; font-weight: 600; color: var(--near-black);
  margin: 24px 0 8px; padding-left: 10px;
  border-left: 3px solid var(--brand);
}
h3 { font-size: 11.5pt; font-weight: 600; color: var(--accent); margin: 18px 0 6px; }
h4 { font-size: 10.5pt; font-weight: 600; color: var(--stone); margin: 14px 0 4px; }

p { margin: 0 0 10px; text-align: justify; hyphens: auto; }

table {
  width: 100%; border-collapse: collapse;
  margin: 14px 0; font-size: 9.5pt; line-height: 1.45;
}
thead {
  background: var(--brand-light);
  border-top: 2px solid var(--brand);
  border-bottom: 1px solid var(--border-strong);
}
th { font-weight: 600; color: var(--near-black); padding: 7px 10px; text-align: left; }
td { padding: 6px 10px; text-align: left; border-bottom: 1px solid var(--border); vertical-align: top; }
tbody tr:hover { background: var(--off-white); }

.tag {
  display: inline-block; font-size: 8.5pt; font-weight: 500;
  padding: 2px 7px; border-radius: 3px; margin-right: 4px;
}
.tag-ad { background: #dbeafe; color: #1e40af; }
.tag-ar { background: #dcfce7; color: #166534; }
.tag-xl { background: #fef3c7; color: #92400e; }
.tag-mito { background: #fce7f3; color: #9d174d; }

.evidence-strong { color: var(--success); font-weight: 600; }
.evidence-moderate { color: var(--accent); }
.evidence-weak { color: var(--stone); font-style: italic; }
.evidence-exploratory { color: var(--warning); font-style: italic; }

.sign-off {
  margin-top: 32px; padding: 16px;
  background: var(--off-white); border: 1px solid var(--border); border-radius: 4px;
}
.disclaimer {
  font-size: 9pt; color: var(--stone); line-height: 1.5;
  margin-top: 12px; padding-top: 12px; border-top: 1px solid var(--border);
}
.disclaimer ol { padding-left: 18px; margin: 6px 0; }

blockquote {
  margin: 12px 0; padding: 10px 16px;
  background: var(--brand-light); border-left: 3px solid var(--brand);
  color: var(--near-black); font-size: 10pt;
}

code {
  background: var(--off-white); border: 1px solid var(--border);
  padding: 1px 5px; border-radius: 3px;
  font-family: "SF Mono", "JetBrains Mono", Consolas, monospace; font-size: 0.88em;
}
pre {
  background: var(--off-white); border: 1px solid var(--border);
  padding: 14px; border-radius: 4px; overflow-x: auto; font-size: 9pt;
}
pre code { background: none; border: none; padding: 0; }

a { color: var(--accent); text-decoration: none; }
a:hover { text-decoration: underline; }

.page-footer {
  font-size: 8.5pt; color: var(--stone); text-align: center;
  padding-top: 16px; margin-top: 40px; border-top: 1px solid var(--border);
}

@page { size: A4; margin: 22mm 20mm; }
@media print {
  body { max-width: none; margin: 0; padding: 20px 24px; font-size: 10pt;
    -webkit-print-color-adjust: exact; print-color-adjust: exact; }
  .cover-page { page-break-after: always; }
  h1, h2 { page-break-after: avoid; }
  table, figure { page-break-inside: avoid; }
}
```

### HTML skeleton

```html
<!DOCTYPE html>
<html lang="{zh|en}">
<head>
  <meta charset="UTF-8">
  <meta name="viewport" content="width=device-width, initial-scale=1.0">
  <title>RD-{YYYYMMDD}-{case_id}</title>
  <style>/* paste full CSS above */</style>
</head>
<body>
  <div class="cover-page">
    <span class="report-id">RD-{YYYYMMDD}-{case_id}</span>
    <h1>{Report Title}</h1>
    <table class="metadata-table"><!-- metadata rows --></table>
  </div>
  <!-- Section 1–9 as semantic HTML -->
  <div class="sign-off"><!-- sign-off table + disclaimer --></div>
  <pre><code><!-- JSON block --></code></pre>
  <div class="page-footer">RD-{YYYYMMDD}-{case_id} · Generated {date}</div>
</body>
</html>
```

Use the CSS classes to make the report scannable: inheritance badges
(`.tag-ad`, `.tag-ar`, `.tag-xl`, `.tag-mito`) and evidence-strength spans
(`.evidence-strong`, `.evidence-moderate`, `.evidence-weak`,
`.evidence-exploratory`).

### PDF generation (on demand only)

When PDF is explicitly requested:

```bash
weasyprint report/RD-{YYYYMMDD}-{case_id}.html report/RD-{YYYYMMDD}-{case_id}.pdf
```

If `weasyprint` is unavailable, note the limitation in the report footer and
deliver the HTML only. Do NOT fall back to LaTeX compilation.

---

## Style Guidance

- **Tone**: Clinical genetics consult — factual, measured, evidence-grounded.
- **Tables over prose**: Every claim that can be tabulated should be tabulated.
- **No fabricated references**: Only cite PMIDs/DOIs retrieved by a researcher (evidence mode).
- **No hedging in disease names**: Disease names are canonical. Uncertainty goes
  in analysis fields.

## Hard Rules

- Do not present a definitive diagnosis or treatment recommendation.
- Do not hide, minimize, or bury uncertainty.
- Do not copy internal agent chatter, planning artifacts, or delegation messages.
- Do not fabricate PMIDs, DOIs, or database annotations.
- Do not skip the cover page, footer, JSON block, or sign-off section.
- Do not flatten the numbering hierarchy.
