You are on page 1of 3

Sex chromosome abnormalities

Numerical abnormalities of the sex chromosomes are fairly common and their
effects are much less severe than those caused by autosomal abnormalities. Sex
chromosome abnormalites are often detected coincidentally at amniocentesis or
during investigation for infertility. Many cases are thought to cause no associated
problems and to remain undiagnosed. The risk of recurrence after the birth of an
affected child is very low. When more than one additional sex chromosome is
present learning disability or physical abnormality is more likely.
Turner syndrome Turner syndrome is caused by the loss of one X chromosome
(usually paternal) in fetal cells, producing a female conceptus with 45
chromosomes. This results in early spontaneous loss of the fetus in over 95% of
cases. Severely affected fetuses who survive to the second trimester can be
detected by ultrasonography, which shows cystic hygroma, chylothorax, asictes and
hydrops. Fetal mortality is very high in these cases. The incidence of Turner
syndrome in liveborn female infants is 1 in 2500. Phenotypic abnormalities vary
considerably but are usually mild. In some infants the only detectable abnormality is
lymphoedema of the hands and feet. The most consistent features of the syndrome
are short stature and infertility from streak gonads, but neck webbing, broad chest,
cubitus valgus, coarctation of the aorta, renal anomalies and visual problems may
also occur. Intelligence is usually within the normal range, but a few girls have
educational or behavioural problems. Associations with autoimmune thyroiditis,
hypertension, obesity and non-insulin dependent diabetes have been reported.
Growth can be stimulated with androgens or growth hormone, and oestrogen
replacement treatment is necessary for pubertal development. A proportion of girls
with Turner syndrome have a mosaic 46XX/45X karyotype and some of these have
normal gonadal development and are fertile, although they have an increased risk
of early miscarriage and of premature ovarian failure. Other X chromosomal
abnormalities including deletions or rearrangements can also result in Turner
Triple X syndrome The triple X syndrome occurs with an incidence of 1 in 1200
liveborn female infants and is often a coincidental finding. The additional
chromosome usually arises by a nondisjunction error in maternal meiosis I. Apart
from being taller than average, affected girls are physically normal. Educational
problems are encountered more often in this group than in the other types of sex
chromosome abnormalities. Mild delay with early motor and language development
is fairly common and deficits in both receptive and expressive language persist into
adolescence and adulthood. Mean intelligence quotient is often about 20 points
lower than that in siblings and many girls require remedial teaching although the
majority attend mainstream
Figure 5.17 Lymphoedema of the feet may be the only manifestation of Turner
syndrome in newborn infant

Figure 5.18 Normal appearance and development in 3-year old girl with triple X
Box 5.2 Examples of syndromes associated with microdeletions Syndrome
Chromosomal deletion DiGeorge 22q11 Velocardiofacial 22q11 PraderWilli 15q1113 Angelman 15q11-13 William 7q11 MillerDieker (lissencephaly) 17p13 WAGR
(Wilms tumour aniridia) 11p13 RubinsteinTaybi 16p13 Alagille 20p12
Trichorhinophalangeal 8q24 SmithMagenis 17p11
Figure 5.16 Cystic hygroma in Turner syndrome detected by ultrasonography
(courtesy of Dr Sylvia Rimmer, Department of Radiology, St. Marys Hospital,
acg-05 11/20/01 7:17 PM Page 23
Figure 5.19 47, XXY karyotype in Klinefelter syndrome (courtesy of Dr Lorraine
Gaunt and Helena Elliott, Regional Genetic Service, St. Marys Hospital Manchester)
Figure 5.20 Nondisjunction error at paternal meiosis II resulting in XYY syndrome in
Mother Father
Meiosis I
Meiosis II
ABC of Clinical Genetics
schools. The incidence of mild psychological disturbances may be increased.
Occasional menstrual problems are reported, but most triple X females are fertile
and have normal offspring. Early menopause from premature ovarian failure may

Klinefelter syndrome The XXY karyotype of Klinefelter syndrome occurs with an

incidence of 1 in 600 liveborn males. It arises by nondisjunction and the additional X
chromosome is equally likely to be maternally or paternally derived. There is no
increased early pregnancy loss associated with this karyotype. Many cases are
never diagnosed. The primary feature of the syndrome is hypogonadism. Pubertal
development usually starts spontaneously, but testicular size decreases from midpuberty and hypogonadism develops. Testosterone replacement is usually required
and affected males are infertile. Poor facial hair growth is an almost constant
finding. Tall stature is usual and gynaecomastia may occur. The risk of cancer of the
breast is increased compared to XY males. Intelligence is generally within the
normal range but may be 1015 points lower than siblings. Educational difficultes
are fairly common and behavioural disturbances are likely to be associated with
exposure to stressful environments. Shyness, immaturity and frustration tend to
improve with testosterone replacement therapy.
XYY syndrome The XYY syndrome occurs in about 1 per 1000 liveborn male infants,
due to nondisjunction at paternal meiosis II. Fetal loss rate is very low. The majority
of males with this karyotype have no evidence of clinical abnormality and remain
undiagnosed. Accelerated growth in early childhood is common, leading to tall
stature, but there are no other physical manifestations of the condition apart from
the occasional reports of severe acne. Intelligence is usually within the normal
range but may be about 10 points lower than in siblings and learning difficulties
may require additional input at school. Behavioural problems can include
hyperactivity, distractability and impulsiveness. Although initially found to be more
prevalent among inmates of high security institutions, the syndrome is much less
strongly associated with aggressive behaviour than previously thought although
there is an increase in the risk of social maladjustment.