During a genetic consultation, it is important to gather information about the pregnancy (see Chapters 58, 59, and 60). A maternal history of a chronic medical condition, such as a seizure disorder or diabetes, has known consequences in the fetus. Medication used in pregnancy can be teratogenic; the pregnant woman’s exposure to toxic chemicals (work related) or use of alcohol, cigarettes, or drugs of abuse can have serious effects on the developing fetus. Maternal infection during pregnancy with varicella, Toxoplasma, cytomegalovirus, and parvovirus B19, among others, has been found to cause malformations in the fetus.
Follow-up is needed if an amniocentesis or CVS reveals abnormal results. A fetal ultrasound may detect a malformation that needs follow-up when the infant is born. Often hydronephrosis is detected prenatally. These infants need a repeat ultrasound soon after birth.
An infant born prematurely is likely to have more complications than a term infant. An infant can be small, appropriate, or large for his or her gestational age; each of these has implications for the child (see Chapters 58, 59, and 60). In general, the finding that an infant is small for gestational age is suggestive of exposure to a teratogen or the presence of a chromosomal abnormality.
Children with inborn errors of metabolism who have intermittent symptoms often have a history of multiple hospitalizations for dehydration or vomiting. Children with neuromuscular disorders may have a normal period followed by increasing weakness or ataxia. Children with lysosomal storage diseases, such as the mucopolysaccharidoses, often have recurrent ear infections and can develop sleep apnea.
Many genetic disorders are associated with developmental disabilities. However, the onset of the disability may not always be present from the newborn period; many inborn errors of metabolism, including storage disorders, cause developmental manifestations after a period of normal development (see Chapters 7 and 8). Some adult-onset disorders have no symptoms until the teens or later. Assessing school problems is important. The type of learning problem, age at onset, and whether there is improvement with intervention or continued decline all are important for proper assessment.
A careful and thorough physical examination is necessary for all patients with signs, symptoms, or suspicion of genetic disease. Sometimes subtle clues may lead to an unsuspected diagnosis. Features suggestive of a syndrome are discussed in more detail in Chapter 50.
An individual’s chromosomal material, known as the karyotype,can be analyzed using cells capable of dividing. In pediatrics, lymphocytes obtained from peripheral blood are the usual source forsuch cells, but cells obtained from bone marrow aspiration, skinbiopsy (fibroblasts), or, prenatally, from amniotic fluid or chorionic villi also can be used. Cells are placed in culture medium andstimulated to grow, their division is arrested in either metaphaseor prophase, slides are made, the chromosomes are stained withGiemsa or other dyes, and the chromosomes are analyzed.
In metaphase, chromosomes are short, squat, and easy to count. Metaphase analysis should be ordered in children whose features suggest a known aneuploidy syndrome, such as a trisomy or monosomy. Chromosomes analyzed in prophase are long, thin, and drawn out; analysis gives far more details than are seen in metaphase preparations. Prophase analysis is ordered in individuals with multiple congenital anomalies without an obvious disorder.