The diagnosis of SMS is usually confirmed through a clinical blood test called a chromosome analysis. Diagnosis can be made by specific tests to analyze the chromosomes, including a cytogenetic test (karyotype) and FISH (fluorescence in situ hybridization) or by chromosome microarray analysis (also called CGH). Most people with SMS are born with a small deletion (missing section) of one member of their 17th pair of chromosomes. It is the lack of this specific section, known as 17p11.2, which causes a child to develop the features of SMS. The genes commonly deleted in persons with SMS have been narrowed down to a "critical region" and encompass approximately 25 genes. All deletion cases include deletion of the RAI1 gene. In cases where a deletion is not detected, then sequencing of the RAI1 gene should be considered. About 90% of the cases of SMS are due to deletion, with the remaining 10% due to a mutation that occurs within the RAI1 gene.
Until the mid-1990's, SMS was not well known, even among genetics professionals. The tiny 17p11.2 deletion was often overlooked in the laboratory, and chromosome results were reported as 'normal'. The recent development of a specific genetic test, known as FISH for 17p11.2 deletion, has allowed more accurate detection of SMS. Thus, a repeat cytogenetic study including FISH is indicated for individuals with prior "normal" routine cytogenetic analysis in whom a diagnosis of SMS is strongly suspected.
In rare cases, additional analysis may be warranted if a person has a negative FISH result but the diagnosis of SMS is strongly suspected by a professional experienced with SMS. For more information about diagnosing SMS, please read the in-depth review of SMS.
The picture on the right is of an individual's chromosomes. The white arrows point to the chromosomes 17p11.2 region. The red-orange signal (or light) is a control used to locate both chromosomes 17. This red-orange probe identifies the long arm of chromosomes 17. The green signal is the test probe on the short arm of chromosome 17 containing the RAI1 gene. The green signal is only seen on one of the chromosomes 17, indicating that the individual is deleted for this region of 17p11.2 located within the SMS region. These results indicate a diagnosis of Smith-Magenis syndrome.
Although SMS is caused by a deletion of genetic material, it usually does not run in families. In most cases, the deletion occurs accidentally in a child around the time he or she is conceived, without being inherited from either parent. For this reason, we can say that SMS is clearly genetic, but not usually familial. Families are advised to consult a genetic counselor or specialist for further advice regarding their own particular family situation. If you need help finding a genetic counselor in your area, please see the NSGC's (National Society of Genetic Counselors') on-line directory.
A genetics counselor may refer you to a geneticist - a medical doctor or medical researcher. A medical geneticist has completed a fellowship or has other advanced training in medical genetics. While a genetic counselor may help you with testing decisions and support issues, a medical geneticist will make the actual diagnosis of a disease or condition such as SMS.