Familial carpal tunnel syndrome due to amyloidogenic transthyretin His 114 variant

Abstract

We studied two patients from a Japanese family with carpal tunnel syndrome (CTS). The biopsy samples obtained during CTS surgical release revealed deposits of amyloid that stained with antihuman transthyretin (TTR) antiserum. Single-strand conformation polymorphism analysis and sequence analysis of polymerase chain reaction (PCR)-amplified exons of the proband's TTR gene revealed a point mutation resulting in a substitution of histidine for tyrosine at position 114. The mutation was confirmed by PCR-primer-induced restriction analysis. Our findings account for clinical heterogeneity of TTR-derived amyloidosis, and suggest the importance of substitution itself for deposits of amyloid in CTS.

Is there a familial carpal tunnel syndrome? An evaluation and literature review

“…17 On further examination these disorders are usually discovered (e.g., a cardiomyopathy in the proband or family suggests amyloidosis, while palsies after minor trauma suggest HNPP). 8,12,19,24,27 In HNPP, testing for the chromosome 17p11.2-12 deletion may make a definitive diagnosis. A subset of patients exists for whom CTS segregates as an isolated autosomal dominant trait-a mononeuropathy with familial predisposition, without evidence of systemic disease.…”

Clinical Reasoning: A 79-year-old man with polyneuropathy and dysautonomia

“…Carpal tunnel syndrome is often an early feature and may be the only clinical manifestation. 5 The recurrent laryngeal nerve may be involved, manifesting as vocal hoarseness. 6 The "scalloped pupil" deformity, which is due to amyloid deposition in the ciliary nerve is pathognomonic for FAP.…”

“…6 The "scalloped pupil" deformity, which is due to amyloid deposition in the ciliary nerve is pathognomonic for FAP. 5 Vitreous opacities are more common, seen in 20% of those with TTR mutations and may be the first manifestation of FAP. 6 Restrictive cardiomyopathy is an important cause of morbidity and mortality in patients with TTR amyloidosis.…”

Identification of a New Transthyretin Variant (Ile49) in Familial Amyloidotic Polyneuropathy Using Electrospray Ionization Mass Spectrometry and Nonisotopic RNase Cleavage Assay

“…Although it has been difficult to treat hereditary amyloidoses, liver transplantation for FAP patients is now considered a promising therapy [6, 7, 8, 9]and better results are obtained if the operation is performed in the early stage of FAP. Sometimes it is very difficult to diagnose FAP clinically, because some patients with TTR-related amyloidosis lack typical FAP symptoms [15, 16, 17]. 2 3 4 Thus, it is important to establish a rapid and reliable method for diangosis.…”