Peripheral nervous system involvement in Klippel-Trenaunay syndrome.

Klippel-Trenaunay syndrome (KTS) is a rare congenital malformation of unknown etiology characterized by cutaneous hemangiomas, venous varicosities and bony and soft tissues hypertrophy usually affecting one limb. Several complex anomalies involving various organs and systems have been described, whereas involvement of the peripheral nervous system has rarely been reported in KTS. We describe the case of a 67-year-old woman with KTS and peripheral neuropathy related to the presence of epineurial microscopic arteriovenous anastomoses (AVA) and endoneurial vascular coils in sural nerve biopsy from both hypertrophic and non-hypertrophic limb. The maintenance of AVA has been proposed to be the cause of the hypertrophy. The observation in our patient of AVA in non-hypertrophic limb contrasts with this hypothesis.

Lack of sodium channel mutation in an Italian family with paramyotonia congenita.

OBJECTIVE: To conduct the genotype-phenotype correlation in a family in which several individuals share clinical and electrophysiologic features of paramyotonia congenita (PC). BACKGROUND: PC, hyperkalemic periodic paralysis (HyperPP), and potassium-aggravated myotonias form the group of hereditary sodium channelopathies. Each of these disorders is associated with different point mutations in SCN4A, the gene encoding the alpha-subunit of the adult human skeletal muscle sodium channel. However, in HyperPP families, evidence of a causative gene different from SCN4A has been found. METHODS: We conducted direct clinical examination, electrophysiologic (EMG/electroneurographic) and cardiologic studies, as well as laboratory screening in several affected and nonaffected members of the family. We performed the genotype-phenotype correlation by microsatellite linkage and cDNA-mutation analyses of the SCN4A gene. RESULTS: Affected members in this family showed clinical and electrophysiologic features typical of PC. The disease phenotype segregated with the chromosomal region that includes the SCN4A gene. Analysis of the entire cDNA sequence of the SCN4A gene in the index case disclosed a G3826A transition, which results in the Val1276Ile substitution. However, PCR-single-stranded confirmation polymorphism and direct sequencing analysis of the segment coding for Val-1276 on genomic DNA confirmed the G3826A transition in the index case but was negative in 11 affected members of the family; however, neither mutations nor aberrant splicings causative of the PC phenotype in this family were found on SCN4A. CONCLUSION: The existence of a second gene different from SCN4A that can give rise to a clinical PC phenotype can be speculated upon.

Familial amyloidotic polyneuropathy: description of an Italian kindred.

Familial amyloidotic polyneuropathy (FAP) is a heterogeneous group of genetic disorders characterized by progressive systemic deposition of extracellular amyloid fibrils, mainly affecting the peripheral nervous system (PNS). These disorders, inherited as an autosomal dominant trait, have frequently been described in various ethnic groups, but have rarely been reported in Italy. A 42 year-old man came to our observation for loss of pain and temperature sense in his legs. Clinical and laboratory data pointed to an amyloidotic polyneuropathy. This led us to discover a large italian kindred in which 19 members were affected by FAP. The diagnosis, established in 8 members on the clinical and laboratory findings, was ana-catamnestic in other 11. In this kindred the onset of the disease ranges from 35 to 50 years of age and the course is progressive and often fatal. The early symptoms are mainly related to autonomic disturbances and to peripheral neuropathy. Cardiac and renal involvement occurs frequently and may be life-threatening.