Spinal muscular atrophy (SMA), an autosomal recessive disease, is the most frequent genetic cause of infant mortality, affecting 1 in 10,000 live births and a carrier rate of 1 in 40 to 50. The disorder leads to progressive loss of the alpha motor neurons of the ventral spinal cord and motor nuclei of the lower brainstem causing hypotonia, muscle weakness, and atrophy of variable severity depending on the underlying genotype. SMA has traditionally been classified into four different phenotypes.

Patients with SMA type 1, which is the most common form (~45% of patients), present with symptoms around 0 to 6 months of age. Clinical presentation includes predominant proximal limb weakness, respiratory insufficiency, and poor feeding. Patients also show signs of intercostal muscle weakness, relative to preserved diaphragm strength, and over time develop a bell-shaped chest deformity with signs of paradoxic breathing. Tongue fasciculations are present, while facial and ocular muscle strength are unaffected. Interestingly, cognitive function is normal to above average. Patients usually do not achieve the ability to sit independently (nonsitters) and have a limited life expectancy.

Type 2 SMA, comprising 30% of cases, presents with muscle weakness by the age of 6 to 18 months. Most patients are able to achieve the ability to sit unsupported (sitters), although they may later lose this ability and are almost never able to stand or walk without support. Patients demonstrate proximal muscle weakness, often more pronounced in the lower extremities, tongue atrophy, and fasciculations. Respiratory insufficiency and dysphagia are common, particularly in more severe phenotypes. Given the significant axial muscle weakness, many patients develop significant scoliosis, which in turn often leads to restrictive lung disease and respiratory insufficiency. Aggressive supportive treatments prior to the onset of disease-modifying therapy led to increased life span, with 68.5% of this historic cohort surviving to age 25.

SMA type 3 (15% of cases) usually shows an onset of symptoms that can present from 18 months to adult hood. Patients are generally able to stand or walk without support (walkers), although some lose this ability with ongoing disease progression. Patients may present with symptoms of proximal weakness such as falls, abnormal gait, and difficulty climbing stairs. In contrast to SMA types 1 and 2, type 3 patients generally have a normal life expectancy and do not develop significant respiratory muscle weakness.

The recent development of disease-modifying therapies has changed the phenotypic landscape significantly, and clinical presentations and disease progression have become more diverse. This has changed previous clinical classifications to focus on the functional status of patients (nonsitters, sitters, walkers) or the response treatment (decline, no change, improvement). Therapeutic approaches are discussed in Chapter 14.

اخر الاخبار

اخبار العتبة العباسية المقدسة

متحف الكفيل يباشر صيانة منسوجات تراثية تابعة للعتبة العسكرية المقدسة

العتبة العباسية المقدسة تستذكر مظلومية الإمام الكاظم (عليه السلام) عبر مجلس عزاء

قسم العلاقات العامة يناقش مع منتدى شباب الإسكان إقامة مهرجان تكريم طالبات المدارس المرتديات العباءة في القادسية

سماحة السيد الصافي يدعو إلى توحيد الجهود في تحقيق التراث لضمان الرصانة والدقة وخدمة الساحة العلمية

المزيد

الآخبار الصحية

6 فواكة تساعدك على الشعور بتحسّن عند المرض

حفاظا على صحة العين.. هذا أفضل وقت لتناول فيتامين أ

الاستخدام اليومي لسماعات الأذن.. أخطر مما تتصور !

هل توقيت نشاطك اليومي يؤثر على صحة دماغك؟.. العلماء يجيبون

المزيد

الآخبار التكنلوجية

ابتكار ألماني قد يغيّر مستقبل صناعة البلاستيك

تحديثات وأرباح عبر المشاهدات.. ما الذي تخطط له "لينكد إن"؟

"الكوكايين الوردي".. مخدر جديد يثير قلق السلطات الأميركية

دراسة: تغيّرات في أسلوب القيادة قد تكشف مبكرا عن الخرف !

المزيد

مواضيع ذات صلة

Molecular Testing for Spinal Muscular Atrophy

Genetics of Spinal Muscular Atrophy

Chondrodysplasias are Caused by Mutations in Genes Encoding Type II Collagen & Fibroblast Growth Factor Receptors

The Genetics of Osteogenesis Imperfecta

Molecular Abnormalities of Collagen in Osteogenesis Imperfecta

Prenatal Diagnosis of Hereditary Genetic Diseases

Prenatal Diagnosis of Non-hereditary Genetic Diseases

Clinical Applications of Gene Testing in Muscular Dystrophy

The Genetics of Duchenne Muscular Dystrophy and Becker Muscular Dystrophy

Pathogenic Variants of an Enzyme Inhibitor: α1-Antitrypsin Deficiency

Lysosomal Storage Diseases: A Unique Class of Enzymopathies

Aminoacidopathies