XXXX : a clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features.

@entity1 @entity7960 @entity1952 @entity296 @entity6 @entity409 @entity2319 @entity346 @entity393 @entity427 @entity2055 @entity4653
The clinical features of 115 @entity1 from 90 families with @entity7960 are described. Onset of symptoms was before the age of 25 (mean 10.52) years in all the index cases. An analysis of early cases suggested that limb and @entity2055 and @entity427 in the legs were the only consistent diagnostic criteria within five years of presentation. @entity4653 , signs of @entity409 in the legs and @entity393 and vibration sense are not necessarily present during the first five years of symptoms, but appear to develop eventually in all cases. Scoliosis and ECG evidence of @entity296 were found in over two-thirds of the @entity1 studied; pes cavus, distal amyotrophy, @entity1952 , @entity346 and @entity2319 were all less frequent. The disorder was gradually progressive in all cases. The mean age of losing the ability to walk was 25 years; 95 per cent were chair-bound by the age of 44 years. About 10 per cent of the @entity1 had @entity6 which was controlled by oral hypoglycaemic drugs in one quarter. @entity6 appeared to be associated with a higher incidence of @entity1952 and @entity2319 . @entity6 also clustered within sibships; the risk of an individual with @entity7960 developing @entity6 if an affected sib has it is over 40 per cent. Similarly, @entity296 ran true within affected members of the same sibship, but there were instances of discordance which suggest that the development of the non-neurological features of @entity7960 may be controlled by modifying genes rather than heterogeneity of the main gene. Segregation analysis and an increased consanguinity rate amongst parents of @entity1 (5.55 per cent) confirmed that this disorder is of autosomal recessive inheritance. A study of 101 first degree relatives of the @entity1 with @entity7960 failed to demonstrate any neurological or electrocardiographic abnormalities which could be ascribed to the heterozygous state.
