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.
Hypothenar hammer syndrome (HHS) is a vascular occlusion in humans in the region of the ulna. It is caused by repetitive trauma to the hand or wrist (such as that caused by the use of a hammer) by the vulnerable portion of the ulnar artery as it passes over the hamate bone, which may result in thrombosis, irregularity or aneurysm formation. HHS is a potentially curable cause of Raynauds syndrome, distinct from hand–arm vibration syndrome. Cause
Diagnosis
A physical examination of the hand may show discoloration (blanching, mottling, and/ or cyanosis; gangrene  may be present in advanced cases), unusual tenderness/ a callous over the hypothenar eminence, and fingertip ulcerations and splinter hemorrhages over ulnar digits; if an aneurysm is present, there may also be a pulsatile mass. Allens test will be positive if an occlusion is present and negative if an aneurysm is present. An angiogram may show a "corkscrew" ulnar artery or an occlusion or aneurysm at the hook of the hamate. Treatment
Noninvasive treatments have an 80% success rate; Example: switch jobs, stop smoking, regular finger exercise, surgical options exist for other instances. Epidemiology
HHS, though rare, occurs much more frequently in men than in women (9:1) and principally affects those in their 40s and 50s. == References ==