Craniofacial dysmorphias in a patient with TS

Craniofacial dysmorphias in a patient with TS

One of the most typical findings during the neonatal period is lymphedema in the feet and hands, which is a result of a drainage deficit due to hypoplasia of the lymphatic vessels and is usually transitory, yet it leaves as a sequelae hypoplastic, narrow and convex nails. Said abnormal drainage has visible and persistent consequences in the neck, where pterigium colli or webbed neck, secondary to nuchal hygroma during fetal life, as well as skin folds and a low hair line and ear implantation are attributed to hygrome absorption.

Congenital structural heart diseases affect approximately 40% of TS patients and are an important cause of early mortality. 8 These anomalies include narrowing of the aorta, a bicuspid aortic valve and abnormal pulmonary venous returns. Aortic dilatation occurs in 15–30% of girls with TS 1 and depending on the size, carries a significant risk of dissection. Aortic dissection incidence in TS is estimated at 0.6–1.4% with a median age of 30–35 years of age. 9

Adult patients with TS frequently show electrocardiographic abnormalities, including axis deviation to the right, T-wave abnormalities, accelerated AV conduction and prolongation of the QT-interval, often independent from structural defects. 10 Essential hypertension affects up to a 25% of adolescents and 50% of adult patients.

Pigmentary nevus are frequent, along with telangectasias and keloid scars

A greater susceptibility to endocrine and autoimmune diseases is well-documented in these patients. 11 Thyroid disease has been reported in up to 30%, with hypothyroidism secondary to Hashimoto thyroiditis being the most prevalent affection. Moreover, a pro-atherogenic lipid profile and glucose intolerance with progression to type II diabetes mellitus are also frequent (2–4 times higher risk than the general population), abnormalities which, with a probable intrinsic vasculopathy, explains the high mortality rates by coronary and cerebrovascular diseases. 4 Approximately 85% of patients with a chromosomal formula 45, X have a total loss of germinal cells at birth, 10–15% of these have enough germinal cells to develop a pubertal response and 5% of them have enough germinal cells to allow for pubertal development and spontaneous menstrual cycles, with a premature menopause at around 30 years of age. 12–14 Natural pregnancy is produced in approximately 1–2% of all women with TS, but with a greater risk of loss. 14

Congenital malformations of the urinary system occur in 30–40% of patients. 15 The most frequent malformations are collecting system alterations (20%), horseshoe kidney (10%) and positional abnormalities (5%). Strabismus and farsightedness occur in 25–35% of these girls, increasing the risk of amblyopia. 16 Likewise, other monogenic disorders linked to chromosome X, like Duchenne muscular dystrophy or hemophilia (both A and B), can affect patients with TS.

This aneuploidy originates for the most part from a non-disjunction phenomenon which affects the paternal genome in 60–80% of cases. 3 Around 50–60% of patients present a full X monosomy, which is defined as the absence of the second sexual chromosome and expressed with formula 45, X. Between 20 and 40% represent mosaics of two or more cell lines derived from the same zygote (Chart 2). Mosaicism may be limited to tissues that do not include peripheral blood, making its diagnosis difficult unless studying the affected tissue. 2

Green-red color blindness occurs in ?8%, a higher prevalence than that observed in women without TS due to color blindness deficiency has an X linked inheritance

Structural alterations of the X chromosome can be found in 20% of cases (Fig. 2), the isochromosome of the long arm being most frequent. Moreover, there can also be rings and X chromosome deletion of both the short and the long arms; in 3–5% we are able to find cell lines with a 46, XY complement or Y chromosome derived chromosomic markers.