The genetic changes that lead to cerebral maldevelopment and dysmorphic physical features are just beginning to be understood. A connection to genes that code for enzymes of folate has been suggested (among other mechanisms). The genetic aspects, as well as features pertaining to the medical care of these patients, are well summarized by Roizen and Patterson. They emphasize the high frequency of enteric sprue (celiac disease) and hypothyroidism and the need for screening for these conditions.
Laboratory and pathologic findings Brain weight is approximately 10 percent less than average. The convolutional pattern is abnormal. The frontal lobes are smaller than normal and the superior temporal gyri are thin. There are claims of delayed myelination of cerebral white matter and also of immature and poorly differentiated cortical neurons. Alzheimer neurofibrillary changes and neuritic plaques are practically always found in Down patients who are older than 40 years of age, as mentioned.
It is possible to make the diagnosis of Down syndrome by demonstrating the chromosomal abnormalities in cells of the amniotic fluid. About one-third of pregnant mothers also have an abnormal elevation of serum alpha-fetoprotein in the second trimester of pregnancy. Other independent predictors of fetal Down syndrome are elevated serum chorionic gonadotropin and decreased estriol (Haddow et al). One can uncover a considerable proportion of the Down population by prenatal screening for these serum markers and by performing amniocentesis on women with positive tests to search for the chromosomal abnormality. Early detection is aided by the absence on imaging of a nasal bone between 11 and 14 weeks, at which time it is normally detected (Cicero et al).
These are listed here with brief descriptions of their main features.
1. Trisomy 13 (Patau syndrome). Frequency 1 in 2,000 live births, more female than male, average maternal age 31 years, microcephaly and sloping forehead, microphthalmos, coloboma of iris, corneal opacities, anosmia, low-set ears, cleft lip and palate, capillary hemangiomata, polydactyly, flexed fingers, posterior prominence of heels, dextrocardia, umbilical hernia, impaired hearing, hypertonia, severe cognitive impairment, death in early childhood.
2. Trisomy 18. Frequency 1 in 4,000 live births, more in females, average maternal age 34 years, slow growth, occasional seizures, severe cognitive impairment, hypertonia, ptosis and lid abnormalities, low-set ears, small mouth, mottled skin, clenched fists with index fingers overlapping the third finger, syndactyly, rocker-bottom feet, shortened big toe, ventricular septal defect, umbilical and inguinal hernias, short sternum, small pelvis, small mandible, death in early infancy.
3. Cri-du-chat syndrome (deletion in short arm of chromosome 5). Abnormal cry, like a kitten, severe cognitive impairment, hypertelorism, epicanthal folds, brachycephaly, moon face, antimongoloid slant of palpebral fissures, micrognathia, hypotonia, strabismus.
4. Ring chromosomes. Developmental delay with variable physical abnormalities.
5. Klinefelter syndrome (XXY). Only males affected. Eunuchoid appearance, wide arm span, sparse facial and body hair, high-pitched voice, gynecomastia, small testicles, usually developmentally delayed but not severely so; high incidence of psychosis, asthma, and diabetes.