Sebastian syndrome is an extremely rare genetic disease that results in impaired blood clotting function and abnormal platelet formation. Another name for Sebastian syndrome is autosomal dominant macrothrombocytopenia with leukocyte inclusions.
Sebastian syndrome is classified as one of the inherited giant platelet disorders (IGPDs). Platelet cells are components of the blood that play a key role in blood clotting. All IGPDs are associated with bleeding disorders due to improper platelet function and increased platelet cell size. Other IGPDs include May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome, and Bernard-Soulier syndrome. Sebastian syndrome is distinguished from these other IGPDs by subtle differences in the platelet and white blood cell structure and by the lack of symptoms other than bleeding abnormalities.
People affected by Sebastian syndrome have mild, non-life-threatening dysfunction of the blood related to decreased blood clotting function. They may bruise easily or be prone to nosebleeds.
Sebastian syndrome is inherited as an autosomal dominant trait. Autosomal means that the syndrome is not carried on a sex chromosome, while dominant means that only one parent has to pass on the gene mutation in order for the child to be affected with the syndrome.
Genetic studies in the year 2000 proved that Sebastian syndrome is due to a mutation in the gene that encodes a specific enzyme known as nonmuscle myosin heavy chain 9 (the MYH9 gene). The gene locus is 22q11.2, or, the eleventh band of the q arm of chromosome 22. Research has also shown that mutations in the same gene are responsible for May-Hegglin anomaly and Fechtner syndrome, two other inherited giant platelet disorders.
Sebastian syndrome is extremely rare and less than 10 affected families have been reported in the medical literature. Due to the very small number of cases, demographic trends for the disease have not been established. Affected individuals have been identified in Caucasian, Japanese, African-American, Spanish, and Saudi Arabian families, so there does not seem to be any clear ethnic pattern to the disease. Both males and females appear to be affected with the same probability.
Signs and symptoms
The symptoms of Sebastian syndrome include a propensity for nosebleeds, bleeding from the gums, mildly increased bleeding time after being cut, and a tendency to bruise easily. Women may experience heavier than normal menstrual bleeding. People with Sebastian syndrome may experience severe hemorrhage after undergoing surgery for any reason. Some individuals with Sebastian syndrome may not have any observable physical signs of the disorder at all.
Diagnostic blood tests to confirm the decreased blood clotting function seen in Sebastian syndrome may include a complete blood count (CBC) to determine the number of platelets in a blood sample; blood coagulation studies; or platelet aggregation tests.
There are several other disorders, including non-genetic diseases, that can cause symptoms similar to those seen in Sebastian syndrome. A family history of easy bleeding or bruising is an important clue in diagnosing Sebastian syndrome. Once the hereditary nature of the disease is confirmed, establishing a dominant inheritance pattern can separate Sebastian syndrome from other inherited giant platelet disorders.
Microscopic studies of the blood can reveal the enlarged platelets and the specific shape and structure characteristics associated with Sebastian syndrome. These characteristics include a shape that is less disc-like than normal platelets. There are also bluish inclusions, or small foreign bodies, observed in the white blood cells.
Genetic sequencing to confirm the presence of a mutation on the MYH9 gene is another method to positively diagnose Sebastian syndrome, although this would rarely be performed in lieu of other methods.
Treatment and management
No treatment is required for the majority of people affected with Sebastian syndrome. After surgery, platelet transfusion may be required in order to avoid the possibility of hemorrhage. People diagnosed with Sebastian syndrome should be made aware of the risks associated with excessive bleeding.
People with Sebastian syndrome can be expected to have a normal lifespan. The main risk for some patients is the chance of severe bleeding after surgery or injury.
Kunishima, Shinji, et al. "Mutations in the NMMHC-A Gene Cause Autosomal Dominant Macrothrombocytopenia with Leukocyte Inclusions (May-Hegglin Anomaly/Sebastian Syndrome)." Blood (February 15, 2001): 1147-9.
Mhawech, Paulette, and Abdus Saleem. "Inherited Giant Platelet Disorders: Classification and Literature Review." American Journal of Clinical Pathology (February 2000): 176-90.
Young, Guy, Naomi Luban, and James White. "Sebastian Syndrome: Case Report and Review of the Literature." American Journal of Hematology (April 1999): 62-65.
National Heart, Lung, and Blood Institute. PO Box 30105, Bethesda, MD 20824-0105. (301) 592-8573. nhlbiinfo @rover.nhlbi.nih.gov. <http://www.nhlbi.nih.gov>.
National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or (800) 999-6673. Fax: (203) 746-6481. <http://www.rarediseases.org>.
"Sebastian Syndrome." Online Mendelian Inheritance in Man. <http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605249> (20 April 2001).
Paul A. Johnson