NHS DSD Reference Source Pool — Optional Background
Date: Friday 11 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 UCLH, 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.