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.