PE29.1-5 | Chromosomal Abnormalities — Glossary

The classic karyotype of Klinefelter syndrome, with 47 chromosomes including two X chromosomes and one Y chromosome; the most common sex-chromosome aneuploidy in males.

A chromosomal abnormality in which the cell contains a number of chromosomes that is not an exact multiple of the haploid number; trisomy (one extra) and monosomy (one missing) are common aneuploidies.

Narrowing of the aorta, typically at the juxtaductal position near the ductus arteriosus; presents with upper limb hypertension, radio-femoral delay, and diminished femoral pulses; occurs in ~10–15% of Turner syndrome.

Enzymatic conversion of androgens (testosterone) to oestrogens (oestradiol) by the enzyme aromatase, occurring predominantly in adipose tissue; increased relative aromatisation in Klinefelter contributes to gynaecomastia.

Excessive mobility of the joint between the atlas (C1) and axis (C2) vertebrae due to ligamentous laxity, occurring in ~15% of children with Down syndrome; can lead to spinal cord compression.

A congenital heart defect involving a common atrioventricular valve and defects in the atrial and ventricular septa, arising from failure of the endocardial cushions to fuse; the commonest cardiac lesion in Down syndrome.

Immune-mediated destruction of the thyroid gland (Hashimoto's thyroiditis); occurs in 30–50% of adults with Turner syndrome; leads to hypothyroidism requiring thyroxine replacement.

The complete absence of sperm in the ejaculate; in Klinefelter syndrome this is non-obstructive, caused by failure of spermatogenesis due to seminiferous tubule destruction.

A congenital cardiac defect in which the aortic valve has two leaflets instead of three; the most common cardiac abnormality in Turner syndrome, present in approximately 30% of patients.

Small whitish or pale spots arranged in a ring on the iris, resulting from focal hypoplasia of the iris stroma; seen in a proportion of individuals with Down syndrome and occasionally in normal light-coloured irides.

Systematic karyotyping of relatives of an individual found to carry a chromosomal rearrangement (such as a robertsonian translocation), to identify carriers within the family who may be at elevated reproductive risk.

A prenatal invasive diagnostic procedure performed at 10–13 weeks in which placental tissue is aspirated for fetal karyotype and genetic analysis; carries approximately 0.5–1% procedure-related miscarriage risk.

Inward (medial) curvature of a finger due to a hypoplastic or wedge-shaped middle phalanx; most commonly affects the fifth finger and is a minor feature of Down syndrome.

A physiological variant where puberty onset is delayed but eventually occurs spontaneously; testes are soft and of normal size for the developmental stage, distinguishing it from Klinefelter where testes are small and firm.

An increased carrying angle of the elbow; a minor dysmorphic feature seen in Turner syndrome.

A body habitus characterised by arm span greater than height and lower segment greater than upper segment, resulting from androgen-deficient delayed epiphyseal closure; seen in Klinefelter syndrome.

The free beta subunit of human chorionic gonadotropin; elevated in first-trimester combined screening in Down syndrome pregnancies, used alongside PAPP-A and nuchal translucency.

Abnormal gonadal development resulting in streak gonads (fibrous remnants of ovaries) due to accelerated atresia of primordial follicles in the absence of a second X chromosome.

A rare gonadal tumour arising in dysgenetic gonads containing Y-chromosome material; found in 45,X/46,XY mosaicism; prophylactic gonadectomy is performed to prevent malignant transformation.

Pituitary hormones — FSH and LH — that regulate gonadal function; FSH stimulates spermatogenesis (Sertoli cells); LH stimulates testosterone production (Leydig cells); both are markedly elevated in primary gonadal failure.

Recombinant human GH administered to Turner syndrome patients to improve final adult height by addressing SHOX haploinsufficiency; dose ~0.05–0.067 mg/kg/day, started early in childhood.

Benign proliferation of glandular breast tissue in males, caused in Klinefelter syndrome by an increased oestradiol-to-testosterone ratio resulting from peripheral aromatisation of androgens to oestrogens.

Karyotypes with more than one extra sex chromosome, such as 48,XXXY or 49,XXXXY; associated with progressively more severe intellectual disability, skeletal abnormalities, and gonadal failure than classic 47,XXY.

A renal structural anomaly in which the lower poles of the kidneys are fused across the midline; occurs in approximately 30% of Turner syndrome patients; usually asymptomatic but increases UTI and stone risk.

A hormonal pattern characterised by elevated FSH and LH with low sex-hormone levels, resulting from primary gonadal failure where the pituitary over-drives the non-responsive gonads.

An educational approach in which children with disabilities are educated alongside their typically-developing peers in mainstream schools with appropriate support; recommended by IAP for children with Down syndrome.

A hormone produced by Sertoli cells that reflects spermatogenic function; very low or undetectable in Klinefelter syndrome due to seminiferous tubule destruction.

An assisted reproductive technique in which a single sperm is injected directly into an egg; used in combination with TESE in Klinefelter syndrome to achieve fertilisation.

A structural X chromosome abnormality in which the short arm is absent and the long arm is duplicated symmetrically (46,X,i(Xq)); the most common structural variant in Turner syndrome.

A cause of hypogonadotropic hypogonadism (GnRH deficiency plus anosmia); distinguished from Klinefelter by low FSH/LH (not elevated), delayed puberty with normal testicular texture, and typically normal testicular size.

A display of an individual's chromosomes arranged in homologous pairs by size and banding pattern, used to detect numerical and structural chromosomal abnormalities.

A sex-chromosome aneuploidy in phenotypic males characterised by the karyotype 47,XXY (or variants), resulting in primary hypogonadism, azoospermia, and incomplete virilisation.

Interstitial cells of the testis that produce testosterone in response to LH stimulation; partially dysfunctional in Klinefelter syndrome, contributing to androgen deficiency especially after puberty.

Swelling of the extremities due to impaired lymphatic drainage; in Turner syndrome, this is a neonatal feature (pitting oedema of the dorsum of the hands and feet) caused by abnormal lymphatic development.

The presence of only one X chromosome (karyotype 45,X) instead of the normal two sex chromosomes; the most common cytogenetic cause of Turner syndrome.

The presence of two or more genetically distinct cell lines within a single individual, arising from a post-zygotic mutation; in Down syndrome, one line is 46,normal and the other 47,+21.

The presence of two cell lines in Klinefelter syndrome — 46,XY and 47,XXY — resulting from post-zygotic non-disjunction; generally produces a milder phenotype with possible residual spermatogenesis.

The presence of two cell lines in an individual with Turner syndrome — one line with 45,X and another with 46,XX or 46,XY; phenotype is generally milder than in full 45,X monosomy.

Failure of chromosome pairs to separate properly during meiosis or mitosis, resulting in daughter cells with an abnormal chromosome number.

Ultrasound measurement of fluid at the back of the fetal neck at 11–13+6 weeks gestation; increased NT (>3.5 mm) is associated with chromosomal abnormalities including trisomy 21.

Administration of exogenous oestradiol in Turner syndrome to induce pubertal development, maintain bone density, and support cardiovascular health in the absence of endogenous ovarian oestrogen.

Pregnancy-associated plasma protein A; a serum marker that is reduced in Down syndrome pregnancies during the first trimester.

Definitive determination of fetal chromosome or genetic status using invasive testing (CVS or amniocentesis) that provides a fetal karyotype; distinguished from prenatal screening, which only estimates risk.

A segment at the tip of the short arm of the sex chromosomes that escapes X-inactivation; genes here require two copies for normal dosage — their haploinsufficiency in 45,X explains Turner features.

A structural chromosomal rearrangement in which two acrocentric chromosomes fuse at their centromeres, reducing the total chromosome count by one while retaining all genetic material.

Increased space between the first and second toe; a minor dysmorphic feature commonly seen in Down syndrome.

Progressive fibrosis and replacement of the seminiferous tubules in Klinefelter syndrome, leading to non-obstructive azoospermia; the structural basis of infertility in this condition.

A broad, flat chest with widely spaced nipples; the interpapillary distance exceeds 25% of the chest circumference; a characteristic somatic feature of Turner syndrome.

Short stature homeobox gene located in the pseudoautosomal region 1 (PAR1) of the X and Y chromosomes; haploinsufficiency causes the short stature and skeletal abnormalities seen in Turner syndrome.

A single horizontal crease crossing the entire palm, present in ~50% of individuals with Down syndrome (vs ~5% of normal individuals); also called simian crease.

Fibrous, non-functional ovarian remnants found in Turner syndrome resulting from rapid follicle loss during fetal life; they produce no oestrogen, causing primary amenorrhoea and absent puberty.

A surgical procedure in which testicular tissue is biopsied to retrieve sperm directly from the testis for use in assisted reproduction; successful in approximately 50% of men with Klinefelter syndrome.

Administration of exogenous testosterone to males with primary or secondary hypogonadism to achieve virilisation, maintain bone density, and improve quality of life; initiated at early puberty in Klinefelter syndrome.

A proliferation of immature blast cells occurring in ~10% of neonates with Down syndrome that typically resolves spontaneously within 3 months; ~20% progress to acute myeloid leukaemia.

The presence of three copies of chromosome 21 instead of the normal two; the genetic basis of Down syndrome in approximately 95% of cases.

A sex-chromosome aneuploidy in phenotypic females characterised by monosomy X (45,X) or mosaic/structural variants, presenting with short stature, gonadal dysgenesis, and somatic dysmorphic features.

Redundant skin folds running from the mastoid to the acromion in Turner syndrome, caused by resolution of a fetal cystic hygroma; a cardinal somatic feature.

Random inactivation of one X chromosome in each somatic cell of females (and cells with >1 X); the inactivated chromosome forms a Barr body. In 47,XXY males, one X is inactivated, but genes escaping inactivation remain double-dosed and contribute to the phenotype.