# NHS DSD Reference Source Pool — Optional Background

Date: Tuesday 15 September 2026

Type: Letter

## Summary

This document is an optional source pool of NHS / NHS England / NHS Trust references used when researching and organising the DSD-related supporting material.

Its purpose is to preserve the official-source trail behind the patient-prepared DSD material and to make those sources easy to revisit if a clinical feature, test result, or referral question needs checking.

This is not a diagnostic document and does not attempt to establish that any specific DSD condition is present.

The reference library intentionally prioritises:
- NHS
- NHS England
- NHS England Genomics Education / GeNotes
- NHS Trust specialist services, including **University College London Hospitals NHS Foundation Trust (UCLH)**, **Cambridge University Hospitals NHS Foundation Trust (CUH)** and Imperial College Healthcare NHS Trust

Future personal clinical comparisons should be kept separate from this reference document and should only cross-reference the relevant sections below.

## Background

This reference library keeps three functions separate:

- official NHS / NHS specialist references;
- personal clinical observations and possible feature matching;
- GP referral requests.

This document is the optional **official-source layer**.

Related documents should use the following structure:

- **NHS DSD Reference Source Pool — Optional Background** — the official NHS / NHS specialist sources used.
- **Detailed DSD Clinical Background and Feature Cross-Reference** — the patient-prepared DSD-related personal background and feature comparison.
- **GP Cover Letter — Adult DSD Referral** — the referral-focused request.
- **Existing topic records / Long-Term Health Summary** — detailed chronology and wider clinical history.

This structure avoids repeatedly rewriting long personal histories whenever NHS guidance or a new clinical observation needs to be reviewed.

## Details

### 1. Core DSD overview and adult presentation

#### 1.1 NHS England GeNotes — Differences in sex development

Primary use:
- general DSD clinical features;
- chromosomal, gonadal, hormonal and anatomical development;
- visible or clinically identifiable features that may prompt further assessment.

Official source:
- NHS England Genomics Education. **Differences in sex development**
- https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/differences-in-sex-development/

Useful for future comparison with:
- micropenis or enlarged clitoris;
- undescended gonads;
- hypospadias / chordee;
- failure to thrive;
- hyponatraemia / dehydration;
- atypical growth patterns;
- gynaecomastia;
- infertility;
- other DSD-related developmental or pubertal findings.

#### 1.2 NHS — Differences in sex development

Primary use:
- general patient-facing NHS explanation;
- adult first presentation;
- GP and specialist referral pathway.

Official source:
- NHS. **Differences in sex development**
- https://www.nhs.uk/conditions/differences-in-sex-development/

Important navigation point:
- adults who think they may have a DSD can discuss this with a GP, who can consider referral to an appropriate specialist team.

### 2. Current NHS genomic testing routes

#### 2.1 NHS England National Genomic Test Directory

Current reference versions:
- **National Genomic Test Directory for Rare and Inherited Disease — Version 9 (8 April 2026)**
- **Rare and Inherited Disease Eligibility Criteria — Version 9.1 (20 May 2026)**

Official source:
- NHS England. **National Genomic Test Directories**
- https://www.england.nhs.uk/publication/national-genomic-test-directories/

Relevant current clinical indications for future review:

- **R146 — Differences in sex development**
- **R148 — Hypogonadotropic hypogonadism**
- **R150 — Congenital adrenal hypoplasia**
- **R180 — Congenital adrenal hyperplasia diagnostic test**
- **R402 — Premature ovarian insufficiency**
- **R160 — Primary pigmented nodular adrenocortical disease**
- **R314 — Ambiguous genitalia**
- **R468 — Possible sex chromosome aneuploidy or structural rearrangement**

Historical note:
- **R297 Possible structural chromosomal rearrangement — karyotype** was retired in the April 2026 update and replaced by more specific indications. For sex-chromosome aneuploidy or structural rearrangement, the current relevant route is **R468**.

Navigation rule:
- do not rely on page numbers or eligibility wording copied from Version 7;
- use the current Version 9 / 9.1 criteria when performing future feature comparisons.

Navigation summaries:

- **R146 — Differences in sex development**
  - the earlier working summary recorded a confirmed 46,XX or 46,XY karyotype as part of the testing framework, together with at least one listed clinical trigger;
  - example triggers recorded in the earlier draft included ambiguous genitalia, evidence of gonadal dysgenesis and under-virilisation in an individual assigned male at birth;
  - these points are navigation aids only and the current Version 9 / 9.1 wording must be checked before any formal eligibility statement is made.

- **R148 — Hypogonadotropic hypogonadism**
  - relevant when congenital / genetic hypogonadotropic hypogonadism is being considered;
  - should be interpreted together with clinical puberty history and hormone results.

- **R150 — Congenital adrenal hypoplasia**
  - the earlier working summary identified adrenal insufficiency as the central clinical context;
  - this route should not be inferred from nonspecific symptoms alone.

- **R180 — Congenital adrenal hyperplasia diagnostic test**
  - the current working summary records biochemically diagnosed CAH as an important prerequisite;
  - the current criteria include age- and presentation-specific pathways, including some adult presentations.

- **R402 — Premature ovarian insufficiency**
  - the earlier working summary records this as a multi-criterion indication rather than a single-feature test route;
  - current Version 9 / 9.1 wording should be checked before any eligibility conclusion.

- **R160 — Primary pigmented nodular adrenocortical disease**
  - the earlier working summary records either primary pigmented nodular adrenocortical disease or a clinical diagnosis of ACTH-independent Cushing syndrome of unknown aetiology as the relevant context.

- **R314 — Ambiguous genitalia**
  - current navigation route for chromosome-level assessment where ambiguous genitalia is clinically identified;
  - whether genital anatomy meets this clinical description requires professional assessment.

- **R468 — Possible sex chromosome aneuploidy or structural rearrangement**
  - current route relevant to clinical suspicion of sex-chromosome aneuploidy, mosaicism or structural rearrangement;
  - replaced the earlier use of retired R297 for this part of the navigation pathway.

### 3. Puberty, hypogonadism and developmental features

#### 3.1 NHS England GeNotes — Patient aged 18 with delayed puberty

Primary use:
- delayed, incomplete or absent pubertal development;
- physical signs relevant to hypogonadism or DSD assessment.

Official source:
- NHS England Genomics Education. **Presentation: Patient aged 18 with delayed puberty**
- https://www.genomicseducation.hee.nhs.uk/genotes/in-the-clinic/presentation-patient-aged-18-with-delayed-puberty/

Useful future comparison points include:
- micropenis;
- low testicular volume;
- cryptorchidism;
- delayed or incomplete puberty;
- biochemical findings involving LH, FSH and sex hormones.

#### 3.2 NHS England GeNotes — Congenital hypogonadotropic hypogonadism

Primary use:
- CHH / Kallmann syndrome;
- pubertal failure;
- congenital and developmental clinical features.

Official source:
- NHS England Genomics Education. **Congenital hypogonadotropic hypogonadism**
- https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/congenital-hypogonadotropic-hypogonadism/

Useful future comparison points include:
- delayed, absent or arrested puberty;
- micropenis;
- cryptorchidism;
- anosmia / hyposmia;
- mirror movements;
- hearing loss;
- midline abnormalities;
- hypodontia;
- renal agenesis;
- limb abnormalities.

Related genomic route:
- **R148 Hypogonadotropic hypogonadism**

### 4. Specific DSD and related conditions

#### 4.1 NHS — Klinefelter syndrome

Official source:
- NHS. **Klinefelter syndrome**
- https://www.nhs.uk/conditions/klinefelters-syndrome/

Useful future comparison points include:
- developmental delay;
- reading, writing, spelling or attention difficulties;
- low energy;
- tall stature / long limbs;
- broad hips;
- poor muscle tone or slower muscle development;
- reduced facial or body hair;
- small, firm testes;
- gynaecomastia;
- infertility;
- low libido;
- erectile difficulties.

#### 4.2 NHS — Androgen insensitivity syndrome

Official source:
- NHS. **Androgen insensitivity syndrome**
- https://www.nhs.uk/conditions/androgen-insensitivity-syndrome/

Primary use:
- CAIS / PAIS clinical features;
- pubertal and reproductive presentation;
- treatment and hormone-replacement context.

Useful future comparison points may include:
- undescended or partially undescended testes;
- small or underdeveloped penis;
- hypospadias;
- little or no pubic / underarm hair;
- breast development or breast tissue;
- infertility.

Important interpretation rule:
- these are clinical features for comparison only;
- diagnosis depends on specialist assessment and may require hormonal, anatomical, chromosomal and/or genetic investigation.

#### 4.3 NHS England GeNotes — Congenital adrenal hyperplasia

Official source:
- NHS England Genomics Education. **Congenital adrenal hyperplasia**
- https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/congenital-adrenal-hyperplasia/

Primary use:
- CAH-related DSD presentations;
- adrenal and electrolyte-related features.

Potential future comparison points include:
- salt wasting;
- dehydration;
- hyponatraemia;
- ambiguous genitalia;
- under-virilisation;
- micropenis or hypospadias in some forms.

Related genomic route:
- **R180 Congenital adrenal hyperplasia diagnostic test**

#### 4.4 NHS England GeNotes — Turner syndrome

Official source:
- NHS England Genomics Education. **Turner syndrome**
- https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/turner-syndrome/

Primary use:
- sex-chromosome-related DSD;
- short stature;
- ovarian dysgenesis / primary ovarian insufficiency;
- absent or incomplete puberty.

Related genomic route:
- **R468 Possible sex chromosome aneuploidy or structural rearrangement**

#### 4.5 Imperial College Healthcare NHS Trust — MRKH

Official source:
- Imperial College Healthcare NHS Trust. **Mayer-Rokitansky-Küster-Hauser syndrome (MRKH)**
- https://www.imperial.nhs.uk/our-services/gynaecology/conditions-and-treatments/mayer-rokitansky-kuster-hauser-syndrome

Primary use:
- congenital Müllerian / reproductive tract differences;
- associated renal, hearing or skeletal findings in some forms.

### 5. Bone health, hormones and HRT

#### 5.1 UCLH — Complete androgen insensitivity syndrome

Primary DSD-specific reference:
- UCLH. **Complete androgen insensitivity syndrome (CAIS)**
- https://www.uclh.nhs.uk/patients-and-visitors/patient-information-pages/complete-androgen-insensitivity-syndrome-cais

Primary use:
- gonadal management;
- hormone replacement after gonadectomy;
- long-term bone health;
- bone-density monitoring;
- specialist DSD follow-up.

Navigation point:
- in some DSD contexts involving loss or absence of effective gonadal hormone function, hormone replacement may be relevant to long-term health, including bone health.

This does not mean that any current musculoskeletal symptom establishes osteoporosis, metabolic bone disease or hormone deficiency.

#### 5.2 NHS — Androgen insensitivity syndrome treatment

Official source:
- NHS. **Androgen insensitivity syndrome**
- https://www.nhs.uk/conditions/androgen-insensitivity-syndrome/

Primary use:
- hormone treatment and long-term management in AIS.

#### 5.3 NHS — Osteoporosis: causes

Official source:
- NHS. **Osteoporosis — Causes**
- https://www.nhs.uk/conditions/osteoporosis/causes/

Primary use:
- general relationship between reduced sex hormones / hypogonadism and bone-health risk.

#### 5.4 General hormone-deficiency background

Supplementary sources:
- NHS. **Hysterectomy — Considerations**
- https://www.nhs.uk/tests-and-treatments/hysterectomy/considerations/
- NHS. **Hysterectomy**
- https://www.nhs.uk/tests-and-treatments/hysterectomy/

Use:
- general supporting information about ovarian hormone loss, HRT and bone health.

These are not DSD-specific primary references and should not replace UCLH CAIS or other specialist DSD guidance.

### 6. Gonadal surveillance and surgery

#### 6.1 UCLH — Gonadal surveillance / gonadectomy

Official sources:
- UCLH. **Complete androgen insensitivity syndrome (CAIS)**
- https://www.uclh.nhs.uk/patients-and-visitors/patient-information-pages/complete-androgen-insensitivity-syndrome-cais
- UCLH. **Laparoscopic gonadectomy**
- https://www.uclh.nhs.uk/patients-and-visitors/patient-information-pages/laparoscopic-gonadectomy
- UCLH. **Inguinal gonadectomy**
- https://www.uclh.nhs.uk/patients-and-visitors/patient-information-pages/inguinal-gonadectomy

Primary use:
- gonadal tumour-risk discussion;
- surveillance;
- gonadectomy;
- hormone management following gonadectomy.

### 7. Dental and developmental background

#### 7.1 CHH-related hypodontia

Primary source:
- NHS England Genomics Education. **Congenital hypogonadotropic hypogonadism**
- https://www.genomicseducation.hee.nhs.uk/genotes/knowledge-hub/congenital-hypogonadotropic-hypogonadism/

Navigation point:
- GeNotes lists **hypodontia** as a possible clinical feature associated with CHH.

Important limitation:
- unusual tooth count, eruption timing or dental arrangement should not automatically be treated as DSD evidence;
- dental records or professional dental assessment would be required to establish whether hypodontia or another developmental abnormality is present.

Supplementary source:
- NHS England. **Clinical standard for oral health and dental care for children and young people**

### 8. Psychological, social and reproductive support

#### 8.1 Psychological and social support

Official sources:
- NHS. **Differences in sex development**
- https://www.nhs.uk/conditions/differences-in-sex-development/
- UCLH. **Complex congenital gynaecology and differences of sex development**
- https://www.uclh.nhs.uk/patients-and-visitors/patient-information-pages/complex-congenital-gynaecology-and-differences-sex-development
- UCLH. **Women’s Health Psychological Services**
- https://www.uclh.nhs.uk/our-services/find-service/womens-health-1/womens-health-psychological-services-whps

Primary use:
- psychological support;
- sexuality and relationships;
- body image;
- adjustment to diagnosis and specialist care.

#### 8.2 Fertility and reproductive management

Official sources:
- UCLH. **Differences in Sex Development service**
- https://www.uclh.nhs.uk/our-services/find-service/womens-health-1/gynaecology/differences-sex-development
- NHS England. **Congenital Gynaecological Anomalies Service Specification**
- https://www.england.nhs.uk/wp-content/uploads/2019/07/1654-Congenital-Gynaecological-Anomalies-Service-Spec.pdf
- UCLH. **Reproductive Medicine Unit — Counselling service information**
- https://www.uclh.nhs.uk/our-services/find-service/womens-health-1/gynaecology/reproductive-medicine-unit/counselling-service-information

Primary use:
- fertility;
- reproductive options;
- routes to parenthood;
- counselling and multidisciplinary support.

### 9. Specialist referral navigation

#### 9.1 UCLH — Differences in Sex Development service

Official source:
- UCLH. **Differences in Sex Development service**
- https://www.uclh.nhs.uk/our-services/find-service/womens-health-1/gynaecology/differences-sex-development

Navigation points:
- service is intended for adolescents and adults;
- adults may present for the first time without an established childhood DSD diagnosis;
- multidisciplinary input may include endocrinology, gynaecology, psychology, urology, specialist nursing, genetics, radiology and biochemistry;
- available previous clinical history, current symptoms and prior investigation results can support referral.

#### 9.2 Cambridge University Hospitals — Adult DSD clinic

Official source:
- Cambridge University Hospitals. **Multi-disciplinary clinics**
- https://www.cuh.nhs.uk/our-services/gynaecology/gynaecology-clinics-and-wards/multi-disciplinary-clinics/

Navigation points:
- CUH lists an **Adult disorders of sexual differentiation (DSD) clinic** at Addenbrooke’s;
- the public page confirms a multidisciplinary adult service;
- the public page does not provide a detailed pre-referral investigation checklist.

#### 9.3 Research / cohort direction

Reference:
- NIHR BioResource
- https://bioresource.nihr.ac.uk/

Use:
- possible research or cohort participation where clinically or scientifically appropriate.

Important limitation:
- research participation is separate from clinical assessment and should not replace specialist clinical care.

### 10. Adjacent non-DSD clinical references

These sources are retained as adjacent clinical references. They are **not DSD-specific evidence**.

#### 10.1 NHS — Joint hypermobility syndrome

Official source:
- NHS. **Joint hypermobility syndrome**
- https://www.nhs.uk/conditions/joint-hypermobility-syndrome/

Navigation use:
- general NHS information on joint hypermobility;
- notes that a GP may use the **Beighton scoring system** when assessing joint flexibility.

Important limitation:
- joint hypermobility or a high Beighton score does not itself establish DSD.

#### 10.2 Beighton scoring reference

Supplementary non-NHS source:
- The Ehlers-Danlos Society. **Assessing joint hypermobility accurately**
- https://www.ehlers-danlos.com/assessing-joint-hypermobility/

Navigation use:
- movement and scoring illustration for the Beighton score.

Important limitation:
- this is not an NHS source and is retained only as a supplementary reference;
- it should not be treated as part of the NHS DSD evidence library.

### 11. Future reference topics

Official NHS / NHS Trust sources can be added later for:

- sexual function;
- body image;
- gender identity;
- long-term metabolic monitoring;
- cardiovascular monitoring;
- surgery and ethics;
- longitudinal clinical data;
- research follow-up.

These topics should only be added when a sufficiently relevant official source has been identified.

## Questions / Requests

For clinical or referral use:

- Use this document as a reference and navigation aid only.
- Check the current official source before relying on any testing criterion, referral rule, or service detail.
- Keep personal clinical observations separate from official reference material.
- Do not treat symptom overlap or a visible feature as proof of a diagnosis.
- Where a genomic testing route is relevant, distinguish between clinical features, testing eligibility, and specialist diagnostic assessment.

## Notes

- The official reference library should be preserved even when a particular condition later appears unlikely.
- Personal lower-limb, upper-limb, skin, systemic or other clinical records should remain in their dedicated files and only be cross-referenced where relevant.
- Future NHS updates should be incorporated here before relying on downstream referral material.
- This document is a navigation and evidence-organising tool, not a self-diagnosis or request for a specific investigation.