Self-harm, including biting, hitting, head banging, and skin picking, is very common. Behavioral complications in Smith-Magenis syndrome are thought to be worsened by issues with sleeping. Repetitive self-hugging is a behavioral trait that may be unique to Smith–Magenis syndrome. People with this condition may also compulsively lick their fingers and flip pages of books and magazines (a behavior known as "lick and flip"), as well as possessing an impressive ability to recall a wide range of small details about people or subject-specific trivia.Other symptoms can include short stature, abnormal curvature of the spine (scoliosis), reduced sensitivity to pain and temperature, and a hoarse voice. Some people with this disorder have ear abnormalities that lead to hearing loss. Affected individuals may have eye abnormalities that cause nearsightedness (myopia), strabismus, and other problems with vision. Heart and kidney defects also have been reported in people with Smith–Magenis syndrome, though they are less common. Genetics
Smith–Magenis syndrome is a chromosomal condition related to low copy repeats of specific segments of chromosome 17. Most people with SMS have a deletion of genetic material from a specific region of chromosome 17 (17p11.2). Although this region contains multiple genes, recently researchers discovered that the loss of one particular gene the retinoic acid induced 1 or RAI1 is responsible for most of the characteristic features of this condition. Also, other genes within the chromosome 17 contribute to the variability and severity of the clinical features.
The FGD1 gene provides instructions for making a protein that turns on (activates) another protein called Cdc42, which transmits signals that are important for various aspects of development before and after birth.Mutations in the FGD1 gene lead to the production of an abnormally functioning protein. These mutations disrupt Cdc42 signaling, leading to the wide variety of abnormalities that occur in people with Aarskog-Scott syndrome.Only about 20 percent of people with this disorder have identifiable mutations in the FGD1 gene. The cause of Aarskog-Scott syndrome in other affected individuals is unknown. Pathophysiology
The Aarskog–Scott syndrome is due to mutation in the FGD1 gene. FGD1 encodes a guanine nucleotide exchange factor (GEF) that specifically activates Cdc42, a member of the Rho (Ras homology) family of the p21 GTPases. By activating Cdc42, FGD1 protein stimulates fibroblasts to form filopodia, cytoskeletal elements involved in cellular signaling, adhesion, and migration. Through Cdc42, FGD1 protein also activates the c-Jun N-terminal kinase (JNK) signaling cascade, a pathway that regulates cell growth, apoptosis, and cellular differentiation.Within the developing mouse skeleton, FGD1 protein is expressed in precartilaginous mesenchymal condensations, the perichondrium and periosteum, proliferating chondrocytes, and osteoblasts. These results suggest that FGD1 signaling may play a role in the biology of several different skeletal cell types including mesenchymal prechondrocytes, chondrocytes, and osteoblasts.