Diaphragmatic dysfunction in Collagen VI myopathies

Diagnostic approach to the congenital muscular dystrophies

“…While some UCMD patients may not achieve the ability to walk, more commonly walking is achieved for some years, and then is lost again in the late first or early second decade of life due to combined progressive hip contractures and increasing weakness. A steady decline in percent predicted forced vital capacity is observed in virtually all Ullrich patients, leading to predominantly night-time respiratory insufficiency [74–76] in which the diaphragm is disproportionally affected [77,78]. …”

“…Respiratory compromise is also less conspicuous in the Bethlem phenotype, although weakness may progress in adulthood [74,79]. Clinical phenotypes that are intermediate between these two classic presentations include patients with early presentation who are ambulating to late teenage years or young adulthood but still presenting progressive respiratory failure, even while still ambulating [76,78,80], Characteristic skin findings are diagnostically helpful and include a tendency for keloid or atrophic scar formation, striae, soft velvety skin on palms and soles and hyperkerotosis pilaris [81]. Cognition is normal and often advanced for age.…”

The Value of Respiratory Muscle Testing in Children With Neuromuscular Disease

“…27 More recently, a D Pgas to D Pes ratio tending to 1 was found to be useful in detecting diaphragm dysfunction in a small cohort of children with a collagen VI-related myopathy. 7,52 Th is dysfunction of the diaphragm was observed during a maximal voluntary inspiratory maneuver in all the patients irrespective of clinical severity, but was detected during spontaneous breathing in the upright position only in patients with moderate-progressive or early severe disease. Another major fi nding was the weakness of expiratory muscles in all these patients, as evidenced by a very low Pgas cough.…”

“…7,12,27,29,[37][38][39] Th e analysis of the esophageal (Pes) and gastric pressures (Pgas) during spontaneous breathing can be very helpful in children with NMD. 7 Indeed, the measurement of the ratio of the change in Pgas ( D Pgas) to the Pes change ( D Pes) refl ects the relative contribution of the diaphragm and the other respiratory muscles to quiet breathing. 40 Since in healthy subjects the magnitude of the increase in Pgas is greater than the decrease in Pes, the D Pgas to D Pes ratio is more negative than 2 1.…”

“…Indeed, children having a NMD characterized by involvement of the diaphragm should be screened for sleep-disordered breathing. [5][6][7] Moreover, a precise evaluation of the capacity of the inspiratory and expiratory muscles may be important for the understanding of the natural history of the disease. Finally, identifi cation of the most informative respiratory parameters associated with the most rapid decline in case of a progressive disease may optimize patient selection for therapeutic trials with innovative therapies.…”