Other skeletal abnormalities include metaphyseal dysostosis (45% of patients), thoracic dystrophy (rib cage abnormalities in 46% of patients) and costochondral thickening (shortened ribs with flared ends in 32% of patients). Skeletal problems are one of the most variable components of SDS, with 50% affected siblings from the same family discordant for clinical presentation or type of abnormality. Despite this, a careful review of radiographs from 15 patients indicated that all of them had at least one skeletal anomaly, though many were subclinical. Other features include metaphysial dysostosis, mild hepatic dysfunction, increased frequency of infections. Genetics
Shwachman–Diamond syndrome is characterized by an autosomal recessive mode of inheritance. The gene that is mutated in this syndrome, SBDS, lies on the long arm of chromosome 7 at cytogenetic position 7q11. It is composed of five exons and has an associated mRNA transcript that is 1.6 kilobase pairs in length. The SBDS gene resides in a block of genomic sequence that is locally duplicated on the chromosome. The second copy contains a non-functional version of the SBDS gene that is 97% identical to the original gene, but has accumulated inactivating mutations over time. It is considered to be a pseudogene. In a study of 158 SDS families, 75% of disease-associated mutations appeared to be the result of gene conversion, while 89% of patients harbored at least one such mutation.
Several SDS patient groups are advocating for better therapies for SDS, and one organization is focused on driving the therapy development efforts. The challenge is whether the SDS community can come together to support the required research, and whether the organizations can successfully execute a strategy that coordinates the efforts for new therapy development. Epidemiology
It is thought to have an estimated incidence of 1 in 75,000 people. History
The disease was first described as a coherent clinical entity in May 1964 by Bodian, Sheldon, and Lightwood. It was subsequently described by Shwachman, Diamond, Oski, and Khaw in November of the same year. In 2001, linkage analysis in SDS families indicated that affected gene mapped to a large region of human chromosome seven. In 2002, this interval was refined to a region on the long arm of the chromosome next to the centromere.In 2003, a team of researchers led by Johanna Rommens at the Hospital of Sick Children (SickKids) in Toronto, Canada, discovered mutations in the SBDS gene (Shwachman–Bodian–Diamond syndrome) were associated with disease. Eponym
Shwachman–Diamond syndrome, less commonly known as Shwachman–Bodian–Diamond syndrome, is named for Harry Shwachman (1910 – September 12, 1986), an American physician, Martin Bodian (1912 – May 12, 1994), a British ophthalmologist who worked in New York City, and Louis Klein Diamond (May 11, 1902 – June 14, 1999), an American pediatrician. References
Further reading
Foerster (2014). "Ch 37. Inherited Aplastic Anemia Syndromes". In John P. Greer; Daniel A. Arber; Bertil Glader; Alan F. List; Robert T. Means Jr.; Frixos Paraskevas; George M. Rodgers; John Foerster (eds.).