Interatrial block as a first clinical presentation of atrial cardiomyopathy related to a novel LMNA variant: a case report.

Background: Interatrial block (IAB) is a conduction delay in Bachmann's bundle with a well-described association with structural heart disease, supraventricular arrhythmias, and cardiovascular events.

Case Summary: We report the case of an asymptomatic 35-year-old man in whom the presence of IAB at electrocardiogram led to a comprehensive evaluation including speckle-tracking echocardiography, 24 h Holter monitoring, and genetic testing. Speckle-tracking echocardiography demonstrated a decrease in the longitudinal strain of interventricular septum, a typical feature of LMNA-related cardiomyopathy, and decreased indices of left atrial deformation.

Gender effect on onset, prevalence and surgical treatment of cataract in patients with Myotonic Dystrophy type 1.

Myotonic Dystrophy type 1 (DM1) is the most common muscular dystrophy in adults, affecting 1:8000 individuals. It is a multi-systemic disorder involving muscle, heart, endocrine and respiratory apparatus and eye. The eye symptoms can include ptosis, external ophthalmoplegia, epiphora, and early onset cataracts.

De Novo Mutation in KMT2C Manifesting as Kleefstra Syndrome 2: Case Report and Literature Review.

Diagnosis of pediatric intellectual disability (ID) can be difficult because it is due to a vast number of established and novel causes. Here, we described a full-term female infant affected by Kleefstra syndrome-2 presenting with neurodevelopmental disorder, a history of hypotonia and minor face anomalies. A systematic literature review was also performed.

The Role of Gene Mutations in Causing Familial Progressive Cardiac Conduction Disease: A Further Contribution.

Progressive cardiac conduction disease (PCCD) is a relatively common condition in young and elderly populations, related to rare mutations in several genes, including and Familial cases have also been reported. We describe a family with a large number of individuals necessitating pacemaker implantation, likely due to varying degrees of PCCD. The proband is a 47-year-old-patient, whose younger brother died at 25 years of unexplained sudden cardiac death.

Molecular Characterization in 19 South-Italian Patients With Dominant and Recessive Type of Myotonia Congenita.

Myotonia congenita is a genetic disease characterized by impaired muscle relaxation after forceful contraction (myotonia). It is caused by mutations in the gene, encoding the voltage-gated chloride channel of skeletal muscle, ClC-1. According to the pattern of inheritance, two distinct clinical forms have been described, Thomsen disease, inherited as an autosomal dominant trait and Becker disease inherited as an autosomal recessive trait.

Cardiac diseases as a predictor warning of hereditary muscle diseases. The case of laminopathies.

Mutations in the gene are associated with a wide spectrum of disease phenotypes, ranging from neuromuscular, cardiac and metabolic disorders to premature aging syndromes. Skeletal muscle involvement may present with different phenotypes: limb-girdle muscular dystrophy type 1B or -related dystrophy; autosomal dominant Emery-Dreifuss muscular dystrophy; and a congenital form of muscular dystrophy, frequently associated with early onset of arrhythmias. Heart involvement may occur as part of the muscle involvement or independently, regardless of the presence of the myopathy.

Longitudinal evaluation of SMN levels as biomarker for spinal muscular atrophy: results of a phase IIb double-blind study of salbutamol.

Background: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder, due to the loss of function of the survival motor neuron () gene. The first treatment for the condition, recently approved, is based on the reduction of exon 7 skipping in mRNAs produced by a highly homologous gene (). The primary objective of the present study was to evaluate the applicability of the dosage of SMN gene produts in blood, as biomarker for SMA, and the safety of oral salbutamol, a beta2-adrenergic agonist modulating levels.

Digenic Inheritance of Shortened Repeat Units of the D4Z4 Region and a Loss-of-Function Variant in in a Family With FSHD.

Facioscapulohumeral muscular dystrophy (FSHD) is a neuromuscular disorder which is typically transmitted by an autosomal dominant pattern, although reduced penetrance and sporadic cases caused by mutations, are often observed. FSHD may be caused by a contraction of a repetitive element, located on chromosome 4 (4q35). This locus is named and consists of 11 to more than 100 repeated units (RU).

The analysis of myotonia congenita mutations discloses functional clusters of amino acids within the CBS2 domain and the C-terminal peptide of the ClC-1 channel.

Myotonia congenita (MC) is a skeletal-muscle hyperexcitability disorder caused by loss-of-function mutations in the ClC-1 chloride channel. Mutations are scattered over the entire sequence of the channel protein, with more than 30 mutations located in the poorly characterized cytosolic C-terminal domain. In this study, we characterized, through patch clamp, seven ClC-1 mutations identified in patients affected by MC of various severities and located in the C-terminal region.

Upper limb function in Duchenne muscular dystrophy: 24 month longitudinal data.

The aim of the study was to establish 24 month changes in upper limb function using a revised version of the performance of upper limb test (PUL 2.0) in a large cohort of ambulant and non-ambulant boys with Duchenne muscular dystrophy and to identify possible trajectories of progression. Of the 187 patients studied, 87 were ambulant (age range: 7-15.

Is the epicardial left ventricular lead implantation an alternative approach to percutaneous attempt in patients with Steinert disease? A case report.

Steinert's disease or Myotonic Dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder characterized by myotonia, muscle and facial weakness, cataracts, cognitive, endocrine and gastrointestinal involvement, and cardiac conduction abnormalities. Although mild myocardial dysfunction may be detected in this syndrome with age, overt myocardial dysfunction with heart failure is not frequent. Cardiac resynchronization therapy is an effective treatment to improve morbidity and reduce mortality in patients with DM1 showing intra-ventricular conduction delay and/or congestive heart failure.

Heart transplantation in patients with dystrophinopathic cardiomyopathy: Review of the literature and personal series.

Cardiomyopathy associated with dystrophinopathies [Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), X-linked dilated cardiomyopathy (XL-dCM) and cardiomyopathy of Duchenne/Becker (DMD/BMD) carriers] is an increasing recognized manifestation of these neuromuscular disorders and notably contributes to their morbidity and mortality. Dystrophinopathic cardiomyopathy (DCM) is the result of the dystrophin protein deficiency at the myocardium level, parallel to the deficiency occurring at the skeletal muscle level. It begins as a "presymptomatic" stage in the first decade of life and evolves in a stepwise manner toward pictures of overt cardiomyopathy (hypertrophic stage, arrhythmogenic stage and dilated cardiomyopathy).

Management of cardiac involvement in muscular dystrophies: paediatric versus adult forms.

Muscular dystrophies are a group of genetic disorders characterized by muscle degeneration and consequent substitution by fat and fibrous tissue. Cardiac involvement is an almost constant feature in a great part of these diseases, as both primary myocardial involvement and secondary involvement due to respiratory insufficiency, pulmonary hypertension or reduced mobility. Primary myocardial involvement usually begins more precociously compared to the secondary involvement.

Diagnosis of Duchenne Muscular Dystrophy in Italy in the last decade: Critical issues and areas for improvements.

Despite all the advances in diagnosis and management of Duchenne muscular dystrophy over the past 50 years, the average age at diagnosis in most countries in the world around is still around 4-5 years. This retrospective study investigates the age at diagnosis in Italy in the past 10 years. We report findings from 384 boys who were diagnosed with DMD from 2005 to 2014.

Brachydactyly type E in an Italian family with 6p25 trisomy.

Brachydactyly type E is a congenital limb malformation characterized by small hands and feet as a result of shortened metacarpals and metatarsals. Genetic causes of this anomaly are heterogeneous and only partially characterized. In this report we describe an Italian family in which four subjects share brachydactyly type E and a 3 Mb microduplication in region 6p25.

A novel 5q11.2 microdeletion in a child with mild developmental delay and dysmorphic features.

5q11.2 Deletion is a very rare genomic disorder, and its clinical phenotype has not yet been characterized. This report describes a patient with an 8.

The genetic basis of undiagnosed muscular dystrophies and myopathies: Results from 504 patients.

Objective: To apply next-generation sequencing (NGS) for the investigation of the genetic basis of undiagnosed muscular dystrophies and myopathies in a very large cohort of patients.

Methods: We applied an NGS-based platform named MotorPlex to our diagnostic workflow to test muscle disease genes with a high sensitivity and specificity for small DNA variants. We analyzed 504 undiagnosed patients mostly referred as being affected by limb-girdle muscular dystrophy or congenital myopathy.

Novel mutations in LMNA A/C gene and associated phenotypes.

Mutations in the lamin A/C gene (LMNA) have been associated with several phenotypes ranging from systemic to prevalent of muscle, heart, skin, nerve etc. More recently they have been associated with dilated cardiomyopathy (DCM) and severe forms of arrhythmogenic right ventricular cardiomyopathy (ARVC). We report four novel mutations - 3 missense and 1 deletion - in 4 unrelated patients showing different phenotypes, ranging from the early onset congenital form of laminopathy to classical LGMD phenotype, to LGMD and heart involvement.

Timed Rise from Floor as a Predictor of Disease Progression in Duchenne Muscular Dystrophy: An Observational Study.

Background: The role of timed items, and more specifically, of the time to rise from the floor, has been reported as an early prognostic factor for disease progression and loss of ambulation. The aim of our study was to investigate the possible effect of the time to rise from the floor test on the changes observed on the 6MWT over 12 months in a cohort of ambulant Duchenne boys.

Subjects And Methods: A total of 487 12-month data points were collected from 215 ambulant Duchenne boys.

Benefits of glucocorticoids in non-ambulant boys/men with Duchenne muscular dystrophy: A multicentric longitudinal study using the Performance of Upper Limb test.

The aim of this study was to establish the possible effect of glucocorticoid treatment on upper limb function in a cohort of 91 non-ambulant DMD boys and adults of age between 11 and 26 years. All 91 were assessed using the Performance of Upper Limb test. Forty-eight were still on glucocorticoid after loss of ambulation, 25 stopped steroids at the time they lost ambulation and 18 were GC naïve or had steroids while ambulant for less than a year.

Clinical features of patients with dystrophinopathy sharing the 45-55 exon deletion of DMD gene.

Becker muscular dystrophy (BMD) was first described in 1953 by Emile Becker as a benign variant of Duchenne muscular Dystrophy (DMD). Compared with DMD, BMD is clinically more heterogeneous, with initial presentation in the teenage years and loss of ambulation beyond the age of 16 and a wide spectrum of clinical presentations, ranging from only myalgias and muscle cramps to exercise intolerance and myoglobinuria, asymptomatic elevation of serum creatin-kinase, or mild limb-girdle weakness and quadriceps myopathy. About 50% of patients become symptomatic by the age of 10 and the most part by the age of 20 years.

Prevalence of congenital muscular dystrophy in Italy: a population study.

Objective: We provide a nationwide population study of patients with congenital muscular dystrophy in Italy.

Methods: Cases were ascertained from the databases in all the tertiary referral centers for pediatric neuromuscular disorders and from all the genetic diagnostic centers in which diagnostic tests for these forms are performed.

Results: The study includes 336 patients with a point prevalence of 0.

The 6 minute walk test and performance of upper limb in ambulant duchenne muscular dystrophy boys.

The Performance of Upper Limb (PUL) test was specifically developed for the assessment of upper limbs in Duchenne muscular dystrophy (DMD). The first published data have shown that early signs of involvement can also be found in ambulant DMD boys. The aim of this longitudinal Italian multicentric study was to evaluate the correlation between the 6 Minute Walk Test (6MWT) and the PUL in ambulant DMD boys.