Turner syndrome

Constitutional chromosome result

Record the original laboratory result with specimen identity, tissue, method, cell counts and limitations.

1. Which sex-chromosome cell lines or structural alterations were reported, and in what tissue? definition
2. Which report, sampling date, cell count and detection limits support that result? provenance

Classification and surveillance applicability

Record the specialist's diagnostic conclusion separately from any decision to apply Turner surveillance.

1. How were prenatal screening ambiguity, isolated chromosome deletions, alternative syndromes or age-related X loss addressed? boundary
2. If a 45,X/46,XY finding crosses diagnostic conventions, what classification and surveillance plan did the specialist document? action

Interpretable cardiovascular baseline

Retain imaging coverage, segment measurements, indexing method, congenital findings and dated blood pressure results.

1. Which aortic segments, valve morphology and arch features were adequately visualised, and which remain uncertain? measurement
2. Are serial aortic dimensions comparable by segment, technique and body-size reference, and what blood pressure evidence accompanies them? measurement

Cardiovascular review plan

Record the cardiologist's assessment and its consequences for follow-up, activity, pregnancy assessment or intervention review.

1. Which current findings and guideline version support the assigned follow-up interval or activity advice? provenance
2. What symptoms or measurement changes trigger urgent evaluation, and who owns the response? action

Growth potential and response

Record serial growth, skeletal maturation and the rationale and outcome of any growth-directed treatment.

1. What do dated height, growth velocity and skeletal maturation assessments show using explicitly named references? measurement
2. What goal, response, safety observations and patient preference support continuing, changing or ending growth treatment? action

Pubertal course and replacement response

Distinguish endogenous development from treatment-associated changes and document the reviewed replacement plan.

1. Which pubertal changes, menstrual events and hormone results occurred spontaneously or during treatment? measurement
2. What endocrine assessment supports the current estrogen and, where applicable, progestogen plan, including response and tolerability? action

Gonadal function and Y-material review

Link ovarian-function assessments and Y-material findings to an individual specialist interpretation.

1. What evidence supports the current assessment of ovarian function, and what uncertainty remains about future fertility? measurement
2. If Y material is detected or suspected, what gonadal risk discussion, options and agreed decision are documented? action

Individual reproductive decision

Record fertility counselling and preservation discussions separately from pregnancy risk assessment.

1. Which reproductive goals and options has the person chosen to discuss, and what evidence supports their feasibility? action
2. Before attempted pregnancy or embryo transfer, what cardiovascular and maternal-fetal assessments remain unresolved? boundary

Organ findings and functional impact

Record renal anatomy and function, hearing and ear assessments, visual concerns, skeletal findings and lymphoedema when assessed.

1. Which renal, hearing, visual, skeletal or lymphatic findings are documented, absent on assessment or still unassessed? measurement
2. Which findings require specialist follow-up or changes to communication, mobility or daily support? action

Screening results and follow-through

Link thyroid, coeliac, glucose, lipid, liver and bone assessments to dated results and accountable follow-up.

1. Which assessments are applicable and current under the selected guideline, and which abnormal results remain unresolved? measurement
2. How were short stature, hormone exposure and fracture history considered when interpreting bone-density results? boundary

Individual functional profile

Record assessed learning, executive, visuospatial, social and emotional functioning together with the person's account.

1. Which strengths or difficulties are demonstrated by assessment or reported experience rather than assumed from Turner syndrome? provenance
2. What educational, workplace, hearing-access or psychological support does the person want, and has it helped? action

Continuous Turner care plan

Connect surveillance, endocrine treatment, cardiovascular follow-up and reproductive counselling to named services.

1. Which clinician or service owns each outstanding Turner-related assessment, particularly during transfer to adult care? action
2. Can the person access and use their chromosome report, current treatment plan, cardiovascular summary and next-review dates? boundary

Kinds and varieties

Reported by the breadth pass; each item needs checking against its source before it becomes normative.

• 45,X (non-mosaic monosomy X)
• 45,X/46,XX mosaicism
• 45,X/46,XY mosaicism (mixed gonadal dysgenesis spectrum)
• 46,X,i(Xq) isochromosome Xq
• 46,X,r(X) ring X (including small ring X with risk of intellectual disability)
• Xp or Xq deletions / other structural X rearrangements
• 45,X/47,XXX and other complex mosaics

1. Which of these kinds and varieties hold for the sense of Turner syndrome this model covers, and on what evidence? provenance

Identifiers and schemes

Reported by the breadth pass; each item needs checking against its source before it becomes normative.

• Wikidata - Q202768 - Item for Turner syndrome.
• ICD-11 MMS - LD50 - Turner syndrome under sex chromosome aneuploidies.
• ICD-10-CM - Q96.* - Q96.0 Karyotype 45,X; Q96.1 46,X iso (Xq); Q96.2 46,X with abnormal sex chromosome except iso (Xq); Q96.3 Mosaicism, 45,X/46,XX or XY; Q96.4 Mosaicism, 45,X/other cell line(s) with abnormal sex chromosome; Q96.8 Other variants; Q96.9 Unspecified.
• OMIM - 163950 - Phenotypic series / Turner syndrome entry.
• Orphanet - ORPHA:881 - Rare-disease identifier.
• MeSH - D014424 - Turner Syndrome.
• SNOMED CT - 38804009 - Concept for Turner syndrome (disorder); mosaicism and karyotype subtypes have additional codes.
• MONDO - MONDO:0019499 - Turner syndrome disease class.
• Karyotype (ISCN) - 45,X ; 45,X/46,XX ; 45,X/46,XY ; 46,X,i(X)(q10) ; 46,X,r(X) - Laboratory designation of the causal sex-chromosome complement, not a disease code.

1. Which of these identifiers and schemes hold for the sense of Turner syndrome this model covers, and on what evidence? provenance

Standards and regulation

Reported by the breadth pass; each item needs checking against its source before it becomes normative.

• International Turner Syndrome Consensus Group / Endocrine Society-aligned 2016 Cincinnati clinical practice guidelines for diagnosis and lifelong care of girls and women with Turner syndrome (Gravholt et al., European Journal of Endocrinology).
• ACOG / ACMG / related professional guidance on prenatal cell-free DNA screening, diagnostic karyotype or chromosomal microarray confirmation, and counselling when a sex-chromosome aneuploidy is suggested.
• ISCN (International System for Human Cytogenomic Nomenclature, ISCN 2020/2024) for reporting 45,X and mosaic/structural variants.
• WHO ICD-10 Q96 and ICD-11 LD50 as the statistical classification used in health records and rare-disease coding.
• Newborn and childhood growth standards used with condition-specific growth charts (e.g. Lyon/Ranke Turner syndrome charts) rather than general female charts alone.
• National newborn, paediatric endocrinology, and congenital heart programmes implement the consensus rather than a single statute; no unique drug-class marketing authorisation defines the syndrome itself.

1. Which of these standards and regulation hold for the sense of Turner syndrome this model covers, and on what evidence? provenance

Real-world use

Reported by the breadth pass; each item needs checking against its source before it becomes normative.

• Prenatal suspicion from increased nuchal translucency, cystic hygroma, coarctation, horseshoe kidney, or non-invasive prenatal testing showing missing X material, then confirmatory amniocentesis/CVS karyotype or microarray.
• Postnatal diagnosis in a neonate with lymphoedema of hands/feet, webbed neck, left-sided heart lesion, or in a girl investigated for short stature, delayed puberty, or primary amenorrhoea.
• Lifelong multidisciplinary care: paediatric then adult endocrinology (GH then oestrogen/progestin replacement), cardiology (aortic imaging), audiology, fertility counselling, and screening for autoimmune thyroid disease, coeliac disease, and metabolic risk.
• Karyotype, FISH, and chromosomal microarray are used to define mosaicism and Y-chromosome material that changes gonadectomy counselling.
• Epidemiology and health-service planning treat it as a relatively common sex-chromosome aneuploidy (~1 in 2,000-2,500 liveborn females), with many 45,X conceptions lost as miscarriage.

1. Which of these real-world use hold for the sense of Turner syndrome this model covers, and on what evidence? provenance

Typical measurements

Reported by the breadth pass; each item needs checking against its source before it becomes normative.

• Live-birth prevalence among phenotypic females - about 1 in 2,000 to 1 in 2,500 - live female births
• Adult untreated height - approximately 20 cm below population female mean (often ~143-147 cm without GH, depending on parental heights and karyotype) - cm
• Childhood growth hormone dosing (consensus starting range) - 45-50 - µg/kg/day
• Serum FSH (post-gonadal failure / adolescence onward) - markedly elevated (hypergonadotropic range, often tens to >100) - IU/L
• Aortic size index (surveillance for aortopathy) - intervention/concern often discussed around ASI ≥2.5 in adults, with lower thresholds in the presence of bicuspid aortic valve or coarctation - cm/m²
• Blood pressure - hypertension is common from childhood/young adulthood; treat to age-appropriate targets - mmHg
• Hearing threshold (sensorineural and/or conductive loss) - clinically important loss in a large minority to majority by adulthood; serial audiometry rather than a single cut-off - dB HL
• Mosaicism fraction (45,X vs second cell line) - 0-100% 45,X cells depending on tissue; blood karyotype underestimates some mosaics - % cells

1. Which of these typical measurements hold for the sense of Turner syndrome this model covers, and on what evidence? provenance

Failure modes and hazards

Reported by the breadth pass; each item needs checking against its source before it becomes normative.

• Left-sided congenital heart disease (bicuspid aortic valve, coarctation) and progressive aortopathy with risk of aortic dissection, especially in pregnancy or with uncontrolled hypertension.
• Ovarian dysgenesis causing absent puberty, infertility, and unopposed hypo-oestrogen risks (bone, uterus, cardiovascular) if replacement is omitted or delayed.
• If Y-chromosome material is present, risk of gonadoblastoma in streak gonads, which is the usual indication for prophylactic gonadectomy.
• Autoimmune thyroid disease, coeliac disease, abnormal glucose tolerance/diabetes, dyslipidaemia, and fatty liver with excess metabolic risk in adults.
• Recurrent otitis, conductive and sensorineural hearing loss, and speech/learning effects of hearing impairment.
• Lymphoedema, renal malformations (horseshoe kidney), hepatic enzyme elevation, and scoliosis as structural comorbidities.
• Small ring X karyotypes can include intellectual disability when XIST-negative rings fail to inactivate.
• High embryonic lethality of non-mosaic 45,X; liveborn cases are a selected subset, often mosaic in unsampled tissues.
• Misattribution of NIPT sex-chromosome calls without diagnostic confirmation, and missed diagnosis when only a 30-cell blood karyotype is used in a mosaic girl with unexplained short stature.

1. Which of these failure modes and hazards hold for the sense of Turner syndrome this model covers, and on what evidence? provenance

Regional variation

Reported by the breadth pass; each item needs checking against its source before it becomes normative.

• Historical eponyms: Henry Turner (1938, United States) vs Ullrich-Turner or Ullrich-Bonnevie in German-language literature; Seresevskij-Turner in some older Russian sources.
• Age at diagnosis still shifts by health system: prenatal NIPT uptake versus later presentation with short stature where routine paediatric growth screening is weaker.
• Growth-hormone start age, adult-care transition, and access to oocyte donation/IVF vary widely with reimbursement and fertility-law regimes.
• ICD-10 Q96 remains dominant in many billing systems while ICD-11 LD50 is rolling out; mosaic 45,X/46,XY may be coded or clinic-labelled as mixed gonadal dysgenesis rather than Turner syndrome depending on phenotype and service (endocrinology vs DSD surgery).
• Condition-specific growth charts and aortic-imaging intervals follow the 2016 international guideline in many high-resource centres; low-resource settings may diagnose only on amenorrhoea/short stature without cardiac MRI surveillance.

1. Which of these regional variation hold for the sense of Turner syndrome this model covers, and on what evidence? provenance

Neighbouring kinds and how to tell them apart

Reported by the breadth pass; each item needs checking against its source before it becomes normative.

• Noonan syndrome - Noonan is a RASopathy with normal female sex chromosomes; distinguish by karyotype (46,XX) plus PTPN11/other RAS-MAPK gene testing. Shared neck/chest/heart gestalt does not make the diagnosis.
• 46,XX gonadal dysgenesis / premature ovarian insufficiency without Turner karyotype - Hypergonadotropic hypogonadism with short stature and somatic Turner stigmata absent or unexplained; 30-cell karyotype, chromosomal microarray, and if needed buccal/tissue studies exclude occult 45,X mosaicism.
• Mixed gonadal dysgenesis / 45,X/46,XY DSD - Overlaps the mosaic Turner spectrum; presence of Y material, genital ambiguity, and gonadoblastoma risk shift labelling and surgical pathway. FISH/PCR for SRY/Y sequences on the same sample used for karyotype is the separator.
• Klinefelter syndrome (47,XXY) - Opposite sex-chromosome aneuploidy in phenotypic males (tall stature, small testes, infertility); karyotype, not phenotype nicknames, separates them.
• Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome - Müllerian agenesis with normal 46,XX karyotype and usually normal ovarian function; pelvic imaging plus karyotype and gonadotrophins separate MRKH from Turner streak gonads and a present but often small uterus.
• Constitutional delay of growth and puberty / isolated short stature - Normal karyotype, timely (if late) endogenous puberty, and no Turner somatic or cardiac/renal findings; karyotype is indicated in unexplained short girls, especially with high FSH.
• Trisomy X (47,XXX) and other sex-chromosome mosaics without a 45,X lineage - Tall or normal stature is typical of 47,XXX; diagnosis is cytogenetic. 45,X/47,XXX mosaics are classified with Turner when a 45,X line is present.

1. Which of these neighbouring kinds and how to tell them apart hold for the sense of Turner syndrome this model covers, and on what evidence? provenance