Embedded Files
with an estimated incidence of 1 in 6,000 to 1 in 10,000 live births, with a carrier frequency of 1/40-1/60 [5,6]. Clinical description and Classification SMA is clinical classified into four phenotypes on the basis of age of onset and motor function achieved [7] (See table 1). SMA type 1 (Werdnig-Hoffmann disease) is the most severe and common type, which accounts for about 50% of patients diagnosed with SMA. Classically infants with SMA type I have onset of clinical signs before 6 months of age, never acquire the ability to sit unsupported and, if no intervention is provided, generally do not survive beyond the first 2 years. These patients have profound * Correspondence: eumercuri@gmail.com 2 Dept of Neurology, Unit of Pediatric Neurology, Catholic University, Largo F. Vito 1, Rome (00168), Italy Full list of author information is available at the end of the article D’Amico et al. Orphanet Journal of Rare Diseases 2011, 6:71 http://www.ojrd.com/content/6/1/71 © 2011 D’Amico et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. hypotonia, symmetrical flaccid paralysis, and often no head control. Spontaneous motility is generally poor and antigravity movements of limbs are not typically observed. In the most severe forms decreased intrauterine movements suggest prenatal onset of the disease and present with severe weakness and joint contractures at birth and has been labeled SMN 0. Some of these children may show also congenital bone fractures and extremely thin ribs [8-11]. Within SMA type I at least 3 clinical subgroups can be defined according to the severity of clinical signs: a) severe weakness since birth/neonatal period, head control is never achieved; b) onset of weakness after the neonatal period but generally within 2 months, head control is never achieved; c) onset of weakness after the neonatal period but head control is achieved. Some of these children may be able to sit with support [12]. Clinically, all children with SMA type I show a combination of severe hypotonia and weakness, with sparing of the facial muscles, invariably associated with a typical respiratory pattern. The weakness is usually symmetrical and more proximal than distal, with lower limbs generally weaker than upper limbs. Deep tendon reflexes are absent or diminished but sensitivity is preserved. The spared diaphragm, combined with weakened intercostal muscles, results in paradoxical breathing. The involvement of bulbar motorneurons often give tongue fasciculation, poor suck and swallow with increasing swallowing and feeding difficulty over time. Aspiration pneumonia is an important cause of morbidity and mortality. In the last few years there has been increasing evidence that some cases with severe SMA type I (generally carrying 1 copy of SMN2) may have heart defects [13,14], mostly atrial and ventricular septal defects and a possible involvement of the autonomic system that may be responsible for arrhythmia and sudden death. SMA type II is characterized by onset between 7 and 18 months of age. Patients achieve the ability to sit unsupported and some of them are able to acquire standing position, but they do not acquire the ability to walk independently. Deep tendon reflexes are absent and fine tremors of upper extremities are common. Joint contractures and kyphoscoliosis are very common and can occur in the first years of life in the more severe type II patients. Weak swallowing can be present but is not common [15] while weakness of the masticatory muscles more often affect the ability to chew. There is a spectrum of severity ranging from weak children who are just able to sit unsupported and are more prone to respiratory signs and early scoliosis to relatively stronger children who have much stronger trunk, limb and respiratory muscles. Patients at the weak end of the spectrum may develop respiratory failure requiring mechanical ventilation. SMA type III (Kugelberg-Welander disease) includes clinically heterogeneous patients. They typically reach all
Report abuse