Rigid spine muscular dystrophy (RSMD) is a form of congenital muscular dystrophy. Disorders in this group cause muscle weakness and wasting (atrophy) beginning very early in life. In particular, RSMD involves weakness of the muscles of the torso and neck (axial muscles). Other characteristic features include spine stiffness and serious breathing problems.\n\nIn RSMD, muscle weakness is often apparent at birth or within the first few months of life. Affected infants can have poor head control and weak muscle tone (hypotonia), which may delay the development of motor skills such as crawling or walking. Over time, muscles surrounding the spine atrophy, and the joints of the spine develop deformities called contractures that restrict movement. The neck and back become stiff and rigid, and affected children have limited ability to move their heads up and down or side to side. Affected children eventually develop an abnormal curvature of the spine (scoliosis). In some people with RSMD, muscles in the inner thighs also atrophy, although it does not impair the ability to walk.\n\nA characteristic feature of RSMD is breathing difficulty (respiratory insufficiency) due to restricted movement of the torso and weakness of the diaphragm, which is the muscle that separates the abdomen from the chest cavity. The breathing problems, which tend to occur only at night, can be life-threatening. Many affected individuals require a machine to help them breathe (mechanical ventilation) during sleep.\n\nThe combination of features characteristic of RSMD, particularly axial muscle weakness, spine rigidity, and respiratory insufficiency, is sometimes referred to as rigid spine syndrome. While these features occur on their own in RSMD, they can also occur along with additional signs and symptoms in other muscle disorders. The features of rigid spine syndrome typically appear at a younger age in people with RSMD than in those with other muscle disorders.

Any centronuclear myopathy in which the cause of the disease is a mutation in the BIN1 gene.

Congenital myopathy-1B (CMYP1B) is an autosomal recessive disorder of skeletal muscle characterized by severe hypotonia and generalized muscle weakness apparent soon after birth or in early childhood with delayed motor development, generalized muscle weakness and atrophy, and difficulty walking or running. Affected individuals show proximal muscle weakness with axial and shoulder girdle involvement, external ophthalmoplegia, and bulbar weakness, often resulting in feeding difficulties and respiratory insufficiency. Orthopedic complications such as joint laxity, distal contractures, hip dislocation, cleft palate, and scoliosis are commonly observed. Serum creatine kinase is normal. The phenotype is variable in severity (Jungbluth et al., 2005; Bharucha-Goebel et al., 2013). Some patients show symptoms in utero, including reduced fetal movements, polyhydramnios, and intrauterine growth restriction. The most severely affected patients present in utero with fetal akinesia, arthrogryposis, and lung hypoplasia resulting in fetal or perinatal death (McKie et al., 2014). Skeletal muscle biopsy of patients with recessive RYR1 mutations can show variable features, including multiminicores (Ferreiro and Fardeau, 2002), central cores (Jungbluth et al., 2002), congenital fiber-type disproportion (CFTD) (Monnier et al., 2009), and centronuclear myopathy (Wilmshurst et al., 2010). For a discussion of genetic heterogeneity of congenital myopathy, see CMYP1A (117000).

Congenital myasthenic syndromes (CMS) are a group of inherited disorders affecting the neuromuscular junction (NMJ). Patients present clinically with onset of variable muscle weakness between infancy and adulthood. These disorders have been classified according to the location of the defect: presynaptic, synaptic, and postsynaptic. CMS10 is an autosomal recessive CMS resulting from a postsynaptic defect affecting endplate maintenance of the NMJ. Patients present with limb-girdle weakness in the first decade. Treatment with ephedrine or salbutamol may be beneficial; cholinesterase inhibitors should be avoided (summary by Engel et al., 2015). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462).

Centronuclear myopathy-5 (CNM5) is an autosomal recessive congenital myopathy characterized by severe neonatal hypotonia with respiratory insufficiency and difficulty feeding. Some patients die in infancy, and some develop dilated cardiomyopathy. Children show severely delayed motor development (summary by Agrawal et al., 2014). For a discussion of genetic heterogeneity of centronuclear myopathy, see CNM1 (160150).

SMALED2A is an autosomal dominant form of spinal muscular atrophy characterized by early childhood onset of muscle weakness and atrophy predominantly affecting the proximal and distal muscles of the lower extremity, although some patients may show upper extremity involvement. The disorder results in delayed walking, waddling gait, difficulty walking, and loss of distal reflexes. Some patients may have foot deformities or hyperlordosis, and some show mild upper motor signs, such as spasticity. Sensation, bulbar function, and cognitive function are preserved. The disorder shows very slow progression throughout life (summary by Oates et al., 2013). For discussion of genetic heterogeneity of lower extremity-predominant spinal muscular atrophy, see SMALED1 (158600).

Congenital myopathy-14 (CMYP14) is an autosomal recessive skeletal muscle disorder characterized by onset of severe muscle weakness apparent at birth and sometimes in utero. Affected infants have difficulty breathing independently and usually require mechanical ventilation for variable lengths of time. Other features include delayed motor development with delayed walking, hypo- or areflexia, and high-arched palate. Skeletal muscle biopsy shows variation in fiber size with specific atrophy of the fast-twitch type II fibers. Cardiac muscle is not affected (summary by Ravenscroft et al., 2018). For a discussion of genetic heterogeneity of congenital myopathy, see CMYP1A (117000).

Congenital myopathy-16 (CMYP16) is an autosomal dominant muscle disorder characterized by onset of hypotonia and tremor in infancy. Patients have mildly delayed walking, unsteady gait, proximal muscle weakness, and a high-frequency tremor of the limbs. Some may develop secondary mild contractures or spinal deformities. Cognition is normal and the disease course tends to stabilize after adolescence (summary by Stavusis et al., 2019). For a discussion of genetic heterogeneity of congenital myopathy, see CMYP1A (117000).

Myofibrillar myopathy-11 (MFM11) is an autosomal recessive skeletal muscle disorder characterized by onset of slowly progressive proximal muscle weakness in the first decade of life. Some patients may present at birth with hypotonia and feeding difficulties, whereas others present later in mid-childhood. Although most patients show delayed walking at 2 to 3 years, all remain ambulatory into adulthood. More variable features may include decreased respiratory forced vital capacity, variable cardiac features, and calf hypertrophy. Skeletal muscle biopsy shows myopathic changes with variation in fiber size, type 1 fiber predominance, centralized nuclei, eccentrically placed core-like lesions, and distortion of the myofibrillary pattern with Z-line streaming and abnormal myofibrillar aggregates or inclusions (summary by Donkervoort et al., 2020). For a phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy, see MFM1 (601419).

Carey-Fineman-Ziter syndrome-2 (CFZS2) is an autosomal recessive disorder characterized by weakness of the facial musculature, hypomimic facies, increased overbite, micrognathia, and facial dysmorphism. Other features may include failure to thrive, axial hypotonia, and progressive scoliosis (Ramirez-Martinez et al., 2022). For a discussion of genetic heterogeneity of Carey-Fineman-Ziter syndrome, see CFZS1 (254940).