Centronuclear myopathies: genotype–phenotype correlation and frequency of defined genetic forms in an Italian cohort

Centronuclear myopathies (CNMs) are a group of clinically and genetically heterogeneous muscle disorders. To date, mutation in 7 different genes has been reported to cause CNMs but 30 % of cases still remain genetically undefined. Genetic investigations are often expensive and time consuming. Clinical and morphological clues are needed to facilitate genetic tests and to choose the best approach for genetic screening. We aimed to describe genotype–phenotype correlation in an Italian cohort of patients affected by CNMs, to define the relative frequencies of its defined genetic forms and to draw a diagnostic algorithm to address genetic investigations. We recruited patients with CNMs from all the Italian tertiary neuromuscular centers following clinical and histological criteria. All selected patients were screened for the four ‘canonical’ genes related to CNMs: MTM1, DNM2, RYR1 and BIN1. Pathogenetic mutations were found in 38 of the 54 screened patients (70 %), mostly in patients with congenital onset (25 of 30 patients, 83 %): 15 in MTM1, 6 in DNM2, 3 in RYR1 and one in TTN. Among the 13 patients with a childhood–adolescence onset, mutations were found in 6 patients (46 %), all in DNM2. In the group of the 11 patients with adult onset, mutations were identified in 7 patients (63 %), again in DNM2, confirming that variants in this gene are relatively more common in late-onset phenotypes. The present study provides the relative molecular frequency of centronuclear myopathy and of its genetically defined forms in Italy and also proposes a diagnostic algorithm to be used in clinical practice to address genetic investigations.     

The Frequency Of Arterial Hypertension Versus Orthostatic Hypotension In Diabetic Patients

Aim: The aim of this study was to assess the relationship between supine high blood pressure and orthostatic hypotension both in Type 1 (T1DM) and Type 2 (T2DM) diabetic patients. Patients and Methods: Our study included 321 T2DM patients (153 M/168 F; mean age 62.3 (14.2 yr; duration of disease 12.1 (7.6 yr) and 116 T1DM patients (65 M/51 F; mean age 39.7 (9.2 yr; duration of diabetes 11.9 (8.1 yr). Patients with orthostatic hypotension were divided into 3 groups: A – without symptoms; B – mild/moderate symptoms (short and tolerable dizziness when standing); C – severe symptoms (persistent and disabling dizziness or even fainting in upright position). Results: Arterial hypertension was registered in 67.6% of T2DM patients (217 from 321 cases) and in 50.0% of T1DM patients (58 from 116 cases). Orthostatic hypotension (defined as a decrease in systolic blood pressure (30 mm Hg)) was encountered in 64.5% in T2DM patients (207 out of 321 cases) and in 60.3% of T1DM patients (70 out of 116 cases). From 207 T2DM patients with orthostatic hypotension, 105 were in Group A (50.7%), 89 in Group B (42.99%) and 13 in Group C (6.28%), while from 70 T1DM patients with orthostatic hypotension 14 were in Group A (20.0%), 51 in Group B (72.8%) and 5 in Group C (7.14%). An association of supine arterial hypertension with orthostatic hypotension was registered in 96 (29.9%) T2DM patients (68 of them receiving antihypertensive treatment) and in 25 (21.5%) T1DM patients (19 of which were on antihypertensive treatment). From the 18 patients with severe orthostatic hypotension (13 T2DM and 5 T1DM), supine arterial hypertension was registered in 5 cases (3 T2DM and 2 T1DM). In 4 of these 5 cases, patients were receiving antihypertensive treatment. Discontinuation of this treatment led to a decrease in the intensity of clinical signs of orthostatic hypotension in 4 out of 5 cases. An improvement of clinical symptoms of orthostatic hypotension was recorded in about 1/3 of hypertensive patients after discontinuation or just lowering of the dose of antihypertensive drugs (26 out of 87 cases). Conclusion: An association between hypertension and orthostatic hypotension is frequent both in T1DM and in T2DM, rising in difficulties for treatment. The treatment of hypertension in diabetic patients should take into account the possible orthostatic hypotension induced by some of the antihypertensive drugs.     

AUTOMA: a wearable device to assess the upper limb muscular activity in patients with neuromuscular disorders

Inherited muscular dystrophies and congenital myopathies present in early childhood with progressive muscle weakness, determining severe motor limitations. Active surveillance and management of associated complications have improved ambulation, function, quality of life and life expectancy. The need for repeatable, objective and quantitative measures to monitor the clinical course of the disease is a current issue, particularly in the new era where new flows of therapies are proposed to the patients. In this scenario, we designed and tested a wearable device termed AUTOMA that is able to provide quantification of the muscular impairment in the upper limb upon isokinetic tests through the integration of a force sensor and an electric goniometer. This allows qualitatively estimating the muscular functions with a systematic procedure. We carried out a preliminary pilot study on 9 patients that revealed the suitability of AUTOMA as an objective measurement tool for diagnosing and monitoring neuromuscular disorders, and opens to a more extensive clinical study in which to test and validate our platform intensively.Key words: neuromuscular disorders, wearable devices, upper limb function, sensing, clinical monitoring, rehabilitation     

Pulmonary venous compartment of the airways circulation

Bronchial circulation has three components: a systemic arterial component represented by the bronchial arteries; a pulmonary venous component represented by the pulmonary veins; and a systemic venous component represented by the bronchial veins. We have used vascular casting, microscope dissection coupled with tracers and light microscopy to define the detailed anatomy of the pulmonary venous compartment of the bronchial circulation. We have found that the extrapulmonary drainage territory of the pulmonary veins correlate with the forming pattern of the right superior pulmonary vein. In the case of a large apical venous trunk, pulmonary veins drain the venous blood of the main bronchia, terminal portion of the trachea and of the tracheobronchial lymph nodes. In the case of the systemic venous drainage of the extrapulmonary airways, we constantly found a pulmonary component which drains the venous blood from the subcarinal lymph nodes and the medial side of the main bronchia.     

Neuropsychiatric outcome in patients with congenital hypothyroidism precautiously treated: Risk factors analysis in a group of patients from Tuscany

AIM: In order to avoid an excessive medical monitoring and to obtain more functional medical controls for the outcome of children with early treated congenital hypothyroidism, the results of a neurological and psychiatric follow-up performed in area Pisana since 1990 are revised. This analysis gives some indications to get over the differences of the various methodological approaches and to get better rehabilitation treatment in respect to the individual needs. METHODS: Our study group includes 52 children with early treated congenital hypothyroidism; a semiquantitative score was used to assess sociocultural level (SCL) of the family. Cognitive and language performances were evaluated by Griffiths Mental Development Scale and with Wechsler Intelligence Scale for Children (WISC-R). RESULTS: Study group mean total scores in cognitive tests are within the normal range, motor and language impairments have been noted, instead. These skills are significantly correlated with pretreatment serum thyroxine (T4). In addition a low SCL is a great risk factor for the occurrence of mild impairments in neuropsychological development. CONCLUSIONS: In arranging the neuropsychological follow-up in early treated congenital hypothyroidism it is recommended to keep in mind the importance of the combination of neonatal endocrinological factors (in particular, pretreatment serum thyroxine) and SCL on the cognitive, motor and language development.     

Comparative high-resolution analysis of linkage disequilibrium and tag single nucleotide polymorphisms between populations in the vitamin D receptor gene

A genome-wide map of single nucleotide polymorphisms (SNP) and a pattern of linkage disequilibrium (LD) between their alleles are being established in three main ethnic groups. An important question is the applicability of such maps to different populations within a main ethnic group. Therefore, we have developed high-resolution SNP, haplotype and LD maps of vitamin D receptor gene region in large samples from five populations. Comparative analysis reveals that the LD patterns are identical in all four European populations tested with two small regions of 1.3 and 5.7 kb at which LD is disrupted completely resulting in three block-like regions over which there is significant and extensive LD. In an African population the pattern is similar, but two additional LD-breaking spots are also apparent. This LD pattern suggests combined action of recombination hotspots and founder effects, but cannot be explained by random recombination and genetic drift alone. Direct comparison indicates that the tag SNPs selected in one European population effectively predict the non-tag SNPs in the other Europeans, but not in the Gambians, for this region.     

Sonography of Non‐neoplastic Disorders of the Hand and Wrist Tendons

Tendon disorders commonly cause hand and wrist disability and curtail the performance of work‐related duties or routine tasks. Imaging is often needed for diagnosis, but it requires knowledge of the complex anatomic structures of the tendons of the hand and wrist as well as familiarity with related disorders. This review article aims to provide medical professionals with guidelines for the sonographic assessment of the tendons of hand and wrist and related disorders. Sonographic features of tendon disorders affecting the hand and wrist are described here, specifically: infectious tenosynovitis; tendon rupture or tearing; stenosing forms of tenosynovitis such as De Quervain disease and trigger finger; intersection syndrome; insertional tendinopathy; several forms of tendinous instability such as extensor carpi ulnaris instability, climber finger, and boxer knuckle; and tendinopathy in inflammatory rheumatic diseases. Postsurgical evaluation of the hand and wrist tendons is also discussed, including the healthy and pathologic appearances of operated tendons as well as impingement from orthopedic hardware. In conclusion, sonography is effective in assessing the tendons of the hand and wrist and related disorders and represents a valuable tool for diagnosis.