Skeleton-Skin-Brain Syndrome: What is it? How does it affect humans?
The Skeleton-Skin-Brain syndrome, also known by the acronym SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans) is a rare genetic disease characterized by skeletal, brain, and skin abnormalities. The disease mainly affects bone development.
People with the disease have underdeveloped bones, which leads to short stature, short legs and arms, shorter fingers, short ribs, curved collar bones, and small skull bones. Compression of the spinal cord and/or upper airway obstruction increases the risk of death in infancy. Apnea (short stops of breathing) is usually present in patients with this disease. Intelligence and life span are usually normal for patients with this genetic disorder.
Additionally, a skin condition known as acanthosis nigricans, also appears in people with Skeleton-Skin-Brain syndrome. Acanthosis nigricans (AN) usually appears in childhood. The Unified Medical Language System (MeSH) of the National Library of Medicine defines AN as “a circumscribed melanosis consisting of a brown-pigmented, velvety verrucosity appearing in the axillae and other body folds."
Genetics of Skeleton-Skin-Brain Syndrome
According to the Genetics Home Reference, this genetic disease is very rare and only a few cases have been described. In fact, incidence of the disease in the global population has not been estimated.
The FGFR3 gene (fibroblast growth factor receptor 3) is responsible for coding a protein factor involved in bone development, bone maintenance and brain tissue development. Mutation in this gene (also known as ACH, CD333, CEK2, FGFR-3, FGR3_HUMAN) causes the resulting coded protein growth factor to be extremely active with the consequence of producing disturbances in growth processes. This leads to all the signs and symptoms of the Skeleton-Skin-Brain syndrome.
The disease is known to have an autosomal dominant type of inheritance. In autosomal dominant diseases, only one copy of the mutated FGFR3 gene in each cell is needed for the disorder to appear in the offspring. However, SADDAN is so rare that no cases of children from affected patients are known to have occurred. On the contrary, all the described cases are the result of natural mutation (de novo mutations) that have developed in the FGFR3 gene.
Are There any Treatments for SADDAN?
SADDAN is a rare, poorly studied and poorly understood genetic disorder. Very few cases have been documented (in 2000 only 3 individuals were observed). Surgical options are available to alleviate issues related to bone shortness. As of 2010, studies are pointing to the possibility that a protein known as Snail1 (which participates in the control of longitudinal bone) may be a new therapeutic target.
Martínez-Frías ML, de Frutos CA, Bermejo E, Nieto MA (2010).
Review of the recently defined molecular mechanisms underlying thanatophoric dysplasia and their potential therapeutic implications for achondroplasia. Am J Med Genet 152A(1):245-55. (https://www.ncbi.nlm.nih.gov/pubmed/20034074)
The FGFR3 gene. Gnetics Home reference (https://ghr.nlm.nih.gov/gene/FGFR3)