Genetic disorder resulting from trisomy 21. Mosaicism
may exist with both trisomic and normal cell lines. Phenotypic expression is
Typical facial features in Trisomy 21.
Down Syndrome; Mongolism.
First described by the English Physician John Langdon
Haydon Down in 1887.
It is the most common human chromosomal syndrome.
Overall, the incidence is about 1:700 live births. However, it is associated with
the parents' age and may affect 1 to 4% of all children born to women
older than 40 years. Furthermore, it is estimated that at least half of the
affected fetuses are aborted spontaneously in early pregnancy.
Nondisjunction during meiosis I (in more than
90% on the maternal side) ultimately results in three separate copies of
chromosome 21 and accounts for 94% of cases. Translocation of the third
chromosome to chromosome 14 or 21 accounts for 3.3% of cases. Abnormal
mitosis in early fetal development may result in mosaicism with one cell
line showing trisomy, the other being of normal karyotype in about 2.4%
of cases. The Down syndrome critical region is located at 21q22.
Chromosomal analysis has been used to assign the
phenotypic features to specific regions of chromosome 21. The region D21S58
to D21S42 is associated with mental retardation and facial features. The
D21S55 locus is linked to many of the phenotypic features of the syndrome.
However, it remains unlikely that a distinct region of chromosome 21
accounts for all the phenotypic features.
Can be made antenatally by chorionic villous sampling or
by amniocentesis. Postnatally, it is made on the basis of clinical features
confirmed by karyotyping.
Common features include brachycephaly with a flat
occiput, malformed ears, epicanthal folds with up-slanting palpebral folds
(mongoloid slanting), strabismus, Brushfield spots on the iris, macroglossia
(although most often the tongue is of normal size, but appears too big in
the context of midface hypoplasia) with furrowing of the tongue (xerostomia,
a consequence of chronic mouth breathing), micrognathia, high-arched palate,
small teeth (microdontia) with abnormal roots, a short, broad neck, and
occipitoatlantoaxial instability. The hands are short and broad with a
single palmar crease, and the middle phalanx of the fifth finger is
hypoplastic. The joints are hypermobile, the muscle tonus is decreased with
poor response to the Moro reflex, and there is usually a gap between the
first and second toes. The angles of the iliac crests and the acetabula are
hypoplastic and short stature is common. Respiratory problems include
subglottic stenosis, obstructive sleep apnea, and recurrent chest
infections. In the presence of uncorrected cardiac defects, pulmonary
hypertension should be assumed—the Eisenmenger complex may be present. Up
to 40% of these patients suffer from congenital cardiac defects,
including endocardial cushion defect (arteriovenous canal abnormalities,
atrial septal defect, ventricular septal defect), patent ductus arteriosus,