TURNER SYNDROME

Turner syndrome is the commonest sex chromosome disorder in females, characterized by a spectrum of phenotype abnormalities and complete or partial absence of one X chromosome.

Incidence of Turner syndrome in female live-births is ~ 1:2500, though the turner genotype (45, XO) is present in 1-2% of conceptions, of which 95% are spontaneously aborted in first trimester.

Cytogenetically, Turner syndrome may be divided into-

(a) classical karyotype (50%), i.e. complete absence of one X chromosomes in all cell lines (45, XO), (b) Mosaicism, i.e. presence of two cell lines (45, XO/46, XX), and

(b) rare structural defects, e.g. deletion of the p or q arm of X chromosome.

As the genes regulating ovarian function and growth (SHOX gene) are present on X chromosome, its complete absence leads to characteristic phenotype of Turner syndrome with short stature and gondal dysgenesis (streak ovaries). However, mosaic cases tend to have milder phenotype and better survival. Deletion of the p arm presents with typical phenotype, while deletion of the q arm is associated with only gonadal dysgenesis without somatic signs.

Clinical spectrum of Turner syndrome is highly variable (Table 11.9) and diagnosis is usually missed at birth. Presence of lymphedema over dorsum of hands/ feet and loose skin folds on the nape of neck are two important signs of Turner syndrome in newborns.

Most cases present later with short stature, small triangular face, anomalous ears, short-webbed neck (Fig. 11.8), wide chest, cubitus valgus with wide carrying angle at elbow, learning disabilities and delayed onset of puberty or menarche.

Congenital heart diseases, specially coarctation of aorta and renal anomalies are common. Hypothyroidism occurs in 15-30% adults with Turner syndrome.

TABLE 11.9: Clinical features of Turner syndrome

• Short stature

• External dysmorphism

- Face: Triangular facies, abnormal ears, cataracts

- Neck: Short, webbed neck, low hairline

- Chest: Broad chest with inter-nipple distance

- Limbs: Carpel/pedal edema, cubitus valgus*

- Skin: Nevi, recurrent keloids, dysplastic nails

• Learning disabilities

• Systemic defects

- CVS: Coarctation of aorta, bicuspid aortic valve, AS

- Renal: Horseshoe shaped or ectopic kidney

- Skeletal: Scoliosis, made-lung deformity, CDH

- Endocrine: Diabetes mellitus, obesity

• Sexual infantilism (Gonadal dysgenesis)

- Delayed puberty

- Amenorrhea/sterility

*Wide carrying angle at elbow gt;110°

Fig. 11.8: Turner syndrome: Webbed neck, widely spaced nipples and cubitus valgus.

Diagnosis is usually made during evaluation for short stature or delayed puberty in girls. Presence of streak ovaries on USG (and absence of germ cells on biopsy) is highly suggestive of Turner syndrome.

Diagnosis needs to be confirmed by karyotyping from peripheral lymphocytes or skin fibroblasts. Buccal smear to detect absence of Barr body is unreliable to exclude Turner syndrome, as it may fail to detect mosaicism and structural defects.

Other investigations are necessary in Turner syn­drome to detect or exclude systemic defects, e.g. echocardiography, abdominal USG, audiometry and serum FSH/LH levels.

Prenatal diagnosis: As recurrence is extremely rare, prenatal diagnosis is indicated only in cases with some antenatal USG markers, e.g. cystic hygroma, lymphedema, hydrops fetalis, left-sided heart defec

and higher fetal heart rate, using cytogenetic studies from chorionic villus sampling or amniocentesis.

Management aims to maximize growth potential and early diagnosis/treatment of medical complications, with:

• Parental counseling, regarding its implications on growth and reproductive failure.

• Periodic evaluation for growth/development, hyper­tension, vision/hearing impairment, thyroid functions, etc.

• Psychosocial support.

• Hormone replacement therapy with growth hormone with/without an androgen, e.g. oxandrolone, is indicated when growth velocity falters and continued till bone age exceeds 14 years. In addition, Estrogen replacement with conjugated estrogen (0.3 mg/day) or ethinylestradiol (5-10 #956;g#8725;day) is indicated at 14 years for 3-6 months, followed by cyclical estrogen/ progesterone therapy to maintain menstrual cycle.

• Prophylactic gonadectomy in cases with streak gonads, to prevent risk of malignancy.

• Assisted reproduction options must be explained to an adult case, as infertility is almost universal.

Noonan syndrome, a variant of Turner syndrome is usually seen in males. These cases usually share some common phenotypic features with Turner syndrome, e.g. short stature and neck-webbing, hence sometimes referred in the past as “male Turner syndromequot; or “female pseudo Turnerquot;. However, it is a single gene disorder affecting the RAS MAPK pathway (Rasopathy) and karyotype is essentially normal.

11.3.3