MedGen

Pompe disease is classified by age of onset, organ involvement, severity, and rate of progression. Infantile-onset Pompe disease (IOPD; individuals with onset before age 12 months with cardiomyopathy) may be apparent in utero but more typically onset is at the median age of four months with hypotonia, generalized muscle weakness, feeding difficulties, failure to thrive, respiratory distress, and hypertrophic cardiomyopathy. Without treatment by enzyme replacement therapy (ERT), IOPD commonly results in death by age two years from progressive left ventricular outflow obstruction and respiratory insufficiency. Late-onset Pompe disease (LOPD; including: (a) individuals with onset before age 12 months without cardiomyopathy; and (b) all individuals with onset after age 12 months) is characterized by proximal muscle weakness and respiratory insufficiency; clinically significant cardiac involvement is uncommon. [from GeneReviews]

Autosomal recessive distal hereditary motor neuronopathy-1 (HMNR1) is characterized by distal and proximal muscle weakness and diaphragmatic palsy that leads to respiratory distress. Without intervention, most infants with the severe form of the disease die before 2 years of age. Affected individuals present in infancy with inspiratory stridor, weak cry, recurrent bronchopneumonia, and swallowing difficulties. The disorder is caused by distal and progressive motor neuronopathy resulting in muscle weakness (summary by Perego et al., 2020). Genetic Heterogeneity of Autosomal Recessive Distal Hereditary Motor Neuronopathy See also HMNR2 (605726), caused by mutation in the SIGMAR1 gene (601978); HMNR3 (607088) (encompassing Harding HMN types III and IV), which maps to chromosome 11q13; HMNR4 (611067), caused by mutation in the PLEKHG5 gene (611101); HMNR5 (614881), caused by mutation in the DNAJB2 gene (604139); HMNR6 (620011), caused by mutation in the REEP1 gene (609139); HMNR7 (619216), caused by mutation in the VWA1 gene (611901); HMNR8 (618912), caused by mutation in the SORD gene (182500); HMNR9 (620402), caused by mutation in the COQ7 gene (601683); HMNR10 (620542), caused by mutation in the VRK1 gene (602168); and HMNR11 (620854), caused by mutation in the RTN2 gene (603183). [from OMIM]

Myofibrillar myopathy-6 is an autosomal dominant severe neuromuscular disorder characterized by onset in the first decade of rapidly progressive generalized and proximal muscle weakness, respiratory insufficiency, cardiomyopathy, and skeletal deformities related to muscle weakness. Muscle biopsy shows fiber-type grouping, disruption of the Z lines, and filamentous inclusions, and sural nerve biopsy shows a neuropathy, often with giant axonal neurons. Most patients are severely affected by the second decade and need cardiac transplant, ventilation, and/or a wheelchair (summary by Jaffer et al., 2012). For a phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy (MFM), see MFM1 (601419). [from OMIM]

Congenital myopathy-10A (CMYO10A) is a severe autosomal recessive skeletal muscle disorder characterized by generalized hypotonia, respiratory insufficiency, and poor feeding apparent from birth. Decreased fetal movements may be observed. More variable features include high-arched palate, distal joint contractures, foot deformities, scoliosis, areflexia, and dysphagia. Many patients show eventration of the diaphragm. Affected individuals become ventilator-dependent in the first months or years of life and never achieve walking; many die in childhood (Logan et al., 2011). Patients with more damaging mutations in the MEGF10 gene, including nonsense or frameshift null mutations, show the more severe phenotype (CMYO10A), whereas those with missense mutations affecting conserved cysteine residues in the EGF-like domain show the less severe phenotype with later onset of respiratory failure and minicores on muscle biopsy (CMYO10B) (Croci et al., 2022). For a discussion of genetic heterogeneity of congenital myopathy, see CMYO1A (117000). [from OMIM]

Autosomal recessive distal hereditary motor neuronopathy-6 (HMNR6) is a neuromuscular disorder characterized by onset of distal muscle weakness in early infancy. Affected individuals often present at birth with distal joint contractures or foot deformities and show delayed motor development, often with inability to walk or frequent falls. Hypo- or hyperreflexia may be observed; limb muscle atrophy may also be present. Patients often show respiratory distress or diaphragmatic palsy. Electrophysiologic studies are consistent with a peripheral motor neuropathy without sensory involvement (Maroofian et al., 2019). For a discussion of genetic heterogeneity of autosomal recessive distal HMN, see HMNR1 (604320). [from OMIM]

The presence of a paralyzed diaphragm. [from HPO]