Chromosome analysis should be ordered for children with multiple congenital anomalies, the involvement of one major organ system and the presence of multiple dysmorphic features, or the presence of mental retardation. In recent years, microarray comparative genomic hybridization has supplanted routine or high-resolution chromosome analysis in most situations. For a complete discussion of chromosome analysis, see Chapter 48.
Direct DNA analysis can be performed to identify specific mutations. It is necessary to use Web-based resources to keep up-to-date. An extremely helpful website is www.genetests.org , which provides information about the availability of testing for specific conditions and identifies laboratories performing the testing.
Radiologic imaging plays an important role in the evaluation of children with dysmorphic features. Individuals found to have multiple external malformations should have a careful evaluation to search for the presence of internal malformations. Testing might include ultrasound evaluations of the head and abdomen to look for anomalies in the brain, kidney, bladder, liver, and spleen. Skeletal radiographs should be performed if there is concern about a possible skeletal dysplasia. The presence of a heart murmur should trigger a cardiology consultation; an electrocardiogram and echocardiogram may be indicated. Magnetic resonance imaging may be indicated in children with neurologic abnormalities or a spinal defect. The presence of craniosynostosis may indicate a computed tomography scan of the head.
For those patients for whom testing does not yield a diagnosis, whole-exome sequencing or whole-genome sequencing is becoming a powerful tool.
Although the presence of characteristic findings may make the diagnosis of a malformation syndrome straightforward, in most cases no specific diagnosis is immediately evident. Some constellations of findings are rare, and finding a “match” may prove difficult. In many cases, all laboratory tests are normal, and confirmation relies on subjective findings. Clinical geneticists have attempted to resolve this difficulty by developing scoring systems, cross-referenced tables of anomalies that help in the development of a differential diagnosis, and computerized diagnostic programs. An accurate diagnosis is important for the following reasons: 1.
It offers an explanation to the family why their child was born with congenital anomalies. This may help allay guilt for parents, who often believe they are responsible for their child’s problem.
2.
With well-described natural histories of many disorders, a diagnosis allows anticipation of medical problems associated with a particular syndrome and appropriate screening. It also provides reassurance that other medical problems are no more likely to occur than they might with other children who do not have the diagnosis.
3.
It permits genetic counseling to be done to identify the risk to future children and permits prenatal testing to be done for the disorders for which it is available.
Diagnosis enables the clinician to provide the family with educational materials about the diagnosis and facilitate contactwith support groups for particular disorders. The Internet hasbecome an important source for such information. Care shouldbe exercised, as information on the Internet is not subject to editorial control and may be inaccurate. A good site is the NationalOrganization for Rare Disorders ( www.rarediseases.org ), a clearinghouse for information about rare diseases and theirsupport groups. Genetic testing information is available at the Genetests website (www.genetests.org ). This site providesinformation on available clinical and research testing for manydiseases.
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