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At a glance

Genetic disorder resulting from trisomy 21. Mosaicism may exist with both trisomic and normal cell lines. Phenotypic expression is variable.

Synonyms

Down Syndrome; Mongolism.

History

First described by the English physician John Langdon Haydon Down in 1887.

Incidence

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.

Genetic inheritance

Nondisjunction during meiosis I (in >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.

Pathophysiology

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.

Diagnosis

Can be made antenatally by chorionic villous sampling or by amniocentesis. Postnatally, it is made on the basis of clinical features confirmed by karyotyping.

Clinical aspects

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 and are much more common in children with Down Syndrome than in the general population. In the presence of uncorrected cardiac defects, pulmonary hypertension should be assumed—the Eisenmenger complex may ...

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