Quantifying gait impairment in individuals affected by Charcot-Marie-Tooth disease: the usefulness of gait profile score and gait variable score.

Gait analysis is a reliable tool to characterise ambulation in Charcot-Marie-Tooth, the obtained are complex data makes its use scarce in clinical practice. The use of synthetic measures may enable the clinician to easily interpret gait kinematics in Charcot-Marie-Tooth. To test the usefulness of Gait Profile Score as a method to quantify and monitor kinematic gait alterations in Charcot-Marie-Tooth.

Charcot-Marie-Tooth disease: genetic subtypes in the Sardinian population.

Charcot-Marie-Tooth disease (CMT) is characterised by great variability of genetic subtypes. This study aimed to assess the genetic subtypes of CMT disease in the Sardinian population. Genetic screening was performed for CMT cases (CMT1, CMT2, and hereditary neuropathy with susceptibility to pressure palsies [HNPP]).

Genotype-phenotype correlation in Pompe disease, a step forward.

Background: Pompe's disease is a progressive myopathy caused by mutations in the lysosomal enzyme acid alphaglucosidase gene (GAA). A wide clinical variability occurs also in patients sharing the same GAA mutations, even within the same family.

Methods: For a large series of GSDII patients we collected some clinical data as age of onset of the disease, presence or absence of muscular pain, Walton score, 6-Minute Walking Test, Vital Capacity, and Creatine Kinase.

Overlapping syndromes in laminopathies: a meta-analysis of the reported literature.

Mutations on the LMNA gene are responsible for an heterogeneous group of diseases. Overlapping syndromes related to LMNA gene alterations have been extensively reported. Study scope is to perform a systematic analysis of the overlapping syndromes so far described and to try to correlate the clinical features to the associated genetic alterations.

Genetic and clinical characteristics of skeletal and cardiac muscle in patients with lamin A/C gene mutations.

Alterations of the lamin A/C (LMNA) gene are associated with different clinical entities, including disorders that affect skeletal and cardiac muscle, peripheral nerves, metabolism, bones, and disorders that cause premature aging. In this article we review the clinical and genetic characteristics of cardiac and skeletal muscle diseases related to alterations in the LMNA gene. There is no single explanation of how LMNA gene alterations may cause these disorders; however, important goals have been achieved in understanding the pathogenic effects of LMNA gene mutations on cardiac and skeletal muscle.

Cardiac involvement in patients with lamin A/C gene mutations: a cohort observation.

Introduction: LMNA gene mutations are associated with cardiac and skeletal muscle alterations.

Methods: A cohort of 21 mutated individuals was assessed with clinical and instrumental investigations over the years.

Results: The median observation period was 6 years.

A novel LRSAM1 mutation is associated with autosomal dominant axonal Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth (CMT) disease is the most common hereditary neuropathy resulting from mutations in >30 genes expressed in either the Schwann cells or the axon of peripheral nerves. The disease is classified into demyelinating (CMT1), axonal (CMT2) or intermediate (CMTI) based on electrophysiological and pathological findings. Our study focused on the identification of a novel disease mutation in a large Sardinian family with CMT2 of autosomal dominant (AD) inheritance.

New motor outcome function measures in evaluation of late-onset Pompe disease before and after enzyme replacement therapy.

Introduction: The clinical course of late-onset Pompe disease is heterogeneous, and new clinical outcome measures are needed to evaluate enzyme replacement therapy (ERT).

Methods: We correlated the 6-Minute Walk Test (6MWT), Walton and Gardner-Medwin (WGM) score, and GSGC (Gait, Stairs, Gower, Chair) scores in 40 patients.

Results: At baseline, the GSGC score correlated with both WGM (P < 0.

Dilated cardiomyopathy with conduction defects in a patient with partial merosin deficiency due to mutations in the laminin-α2-chain gene: a chance association or a novel phenotype?

Patients with a partial reduction of merosin due to mutations in the laminin-α2 chain gene usually present with a mild form of congenital muscular dystrophy or a limb-girdle-like muscular dystrophy. To our knowledge, cardiac impairment has never been reported in such patients. A longitudinal study of a patient with partial laminin-α2 deficiency secondary to mutations in the LAMA2 gene revealed dilated cardiomyopathy with ventricular arrhythmias.

Cardiac and muscle imaging findings in a family with X-linked Emery-Dreifuss muscular dystrophy.

The following is a report on a large family with 5 males affected by the X-linked recessive form of Emery-Dreifuss muscular dystrophy with mutation in the STA gene. A detailed longitudinal cardiological evaluation and muscle imaging studies allowed for the assessment of intrafamilial variability of cardiac and muscle involvement. Long term cardiological follow up in the 5 affected males and in 7 female carriers revealed different degrees of severity, ranging from tachycardia-bradycardia syndrome and variable biatrial and left ventricle dilatation, to an episode of isolated symptomatic sustained ventricular tachycardia requiring a device implantation.

Clinical and molecular characterization of limb-girdle muscular dystrophy due to LAMA2 mutations.

Introduction: In this study we describe the clinical and molecular characteristics of limb-girdle muscular dystrophy (LGMD) due to LAMA2 mutations.

Methods: Five patients clinically diagnosed with LGMD and showing brain white matter hyperintensities on MRI were evaluated using laminin α2 genetic and protein testing.

Results: The patients had slowly progressive, mild muscular dystrophy with various degrees of CNS involvement.

Aberrant splicing in the LMNA gene caused by a novel mutation on the polypyrimidine tract of intron 5.

Introduction: Familial dilated cardiomyopathy with conduction system defects variably associated with skeletal muscle abnormalities is frequently caused by LMNA gene mutations.

Methods: A family affected by cardiac abnormalities, either isolated or variably associated with skeletal muscle compromise, was identified. LMNA gene analysis was applied to all family members.

Heat shock protein 27 R127W mutation: evidence of a continuum between axonal Charcot-Marie-Tooth and distal hereditary motor neuropathy.

Background: Heat shock protein 27 (HSP27) mutations have been reported to cause both Charcot-Marie-Tooth disease (CMT) type 2F and distal hereditary motor neuropathy (dHMN) although never previously in a single family.

Objective: To analyse clinical and electrophysiological findings obtained in a single large Sardinian family bearing the HSP27 R127W mutation.

Methods: Twenty-one members of a five generation Sardinian family have been studied, including thirteen members affected by peroneal muscular atrophy and proved heterozygous for the known HSP27 R127W mutation.

Muscle imaging analogies in a cohort of patients with different clinical phenotypes caused by LMNA gene mutations.

Laminopathies are a heterogeneous group of LMNA-gene-mutation-related clinical disorders associated with alterations of cardiac and skeletal muscle and peripheral nerves, metabolic defects, and premature aging. Leg muscle imaging investigations were performed in a cohort of patients with LMNA gene alterations who were suffering from Emery-Dreifuss muscular dystrophy, limb-girdle muscular dystrophy type 1B, isolated cardiac disorders or a phenotype of cardiac disorders, and lipodystrophy, including one individual with peripheral neuropathy. Leg muscle imaging revealed varying degrees of alteration in the soleus and medial head of gastrocnemius in each subject.

Evolution of the phenotype in a family with an LMNA gene mutation presenting with isolated cardiac involvement.

The aim of this study is to report the evolution of a phenotype in members of a single family carrying the heterozygous exon 1 c.178 C/G, p.Arg 60 Gly LMNA gene mutation.

Muscle MRI findings in patients with an apparently exclusive cardiac phenotype due to a novel LMNA gene mutation.

The case of a family in which several members displayed conduction defects inherited as a dominant trait is reported. The proband was a young woman with a 1st degree atrio-ventricular block and high serum creatine kinase. Several members of the family featured cardiologic symptoms.

A novel mutation in the central rod domain of lamin A/C producing a phenotype resembling the Emery-Dreifuss muscular dystrophy phenotype.

Lamins are the principal components of the nuclear lamina, a network constituting the major structural framework of the nuclear envelope. Alterations in lamin A/C have been associated with a heterogeneous series of human disorders known as laminopathies. We report the finding of a novel deletion in the central rod domain of lamin A/C exon 3 gene in four members of the same family.