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Marie Unna congenital hypotrichosis (MUCH) is a rare autosomal dominant condition in which abnormalities are confined to hair shaft structure and hair density. We report a six-generation pedigree consisting of 59 members of whom 16 are affected; nine identified affected individuals are living. Affected individuals are born with adequate, normal to coarse hair. During early infancy the scalp hair becomes more coarse and wiry and stands out from the head. All affected individuals have sparse to absent eyebrows, eyelashes and body hair including secondary sexual hair. In some individuals, scalp hair is progressively lost beginning at puberty or beyond, until only a sparse fringe in the tonsorial distribution remains. The hair shafts are uniformly increased in diameter, measuring up to 0.12 mm. Individual hair shafts are deeply pigmented, variable in diameter, twisted, and bent at odd angles; some have a longitudinal groove visible on scanning electron microscopy. Cross-sectional shapes are variable and irregular, exhibiting oval, angular to reniform shapes. Multiple anagen hairs are extractable on gentle hair pull. Other ectodermal structures are unaffected except for exceptionally widely spaced upper incisor teeth seen in 50% of affected individuals. Histologically, there are dramatically reduced numbers of follicles per unit area, averaging nine total hairs per 4 mm cross-section as compared with a normal of 40. A mild to moderate inflammatory infiltrate is present, but little fibrosis and no scarring. The mechanism of progressive hair loss is unknown.

CVS-1123, low-molecular-weight, direct thrombin inhibitor was studied in an anesthetized canine model of arterial and venous thrombosis to determine whether thrombin inhibition could reduce the incidence of occlusive thrombosis in response to vessel-wall injury. The left carotid artery (LCA) and right jugular vein (RJV) were instrumented with a flow probe, intraluminal electrode, and critical stenosis. Either saline (n = 9), or CVS-1123 (n = 12) was administered in a loading dose of 2 mg/kg i.v., followed by an infusion (2.46 mg/kg/h for 180 min). Vessel-wall injury was initiated by applying a 300-microA anodal current to the intimal surface of the LCA and RJV. Platelet aggregation in response to gamma-thrombin remained inhibited by CVS-1123 for 8 h. The activated partial thromboplastin time (aPTT) was increased and remained elevated for the duration of the protocol. The prothrombin time (PT) showed an initial increase and then a rapid decrease after the infusion was discontinued. There was a twofold increase in the bleeding time (BT) at 2 h. The time to occlusion of the LCA was prolonged (380 +/- 22 min in the CVS-1123 group vs. 152 +/- 18 min in the saline group) with seven of 12 patent arteries at 8 h. Similarly, the time to occlusion for RJV was prolonged (415 +/- 16 min in the CVS-1123 group vs. 99 +/- 8 min in the saline group) with eight of 12 veins remaining patent at 8 h. CVS-1123 administration was associated with a decrease in the thrombus weights in both the LCA and RJV as compared with the saline-treated animals. In summary, CVS-1123 modifies the thrombogenic response to deep vessel-wall injury in both the arterial and venous circulations. The results suggest that CVS-1123 is an effective antithrombin and may offer a therapeutic alternative to current antithrombins in the management of arterial and venous thrombosis.