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Difficulty climbing stairs

MedGen UID:
68676
Concept ID:
C0239067
Finding
Synonym: Difficulty walking up stairs
SNOMED CT: Difficulty climbing stairs (282195009); Difficulty walking up stairs (282195009)
 
HPO: HP:0003551

Definition

Reduced ability to climb stairs. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVDifficulty climbing stairs

Conditions with this feature

Duchenne muscular dystrophy
MedGen UID:
3925
Concept ID:
C0013264
Disease or Syndrome
The dystrophinopathies cover a spectrum of X-linked muscle disease ranging from mild to severe that includes Duchenne muscular dystrophy, Becker muscular dystrophy, and DMD-associated dilated cardiomyopathy (DCM). The mild end of the spectrum includes the phenotypes of asymptomatic increase in serum concentration of creatine phosphokinase (CK) and muscle cramps with myoglobinuria. The severe end of the spectrum includes progressive muscle diseases that are classified as Duchenne/Becker muscular dystrophy when skeletal muscle is primarily affected and as DMD-associated DCM when the heart is primarily affected. Duchenne muscular dystrophy (DMD) usually presents in early childhood with delayed motor milestones including delays in walking independently and standing up from a supine position. Proximal weakness causes a waddling gait and difficulty climbing stairs, running, jumping, and standing up from a squatting position. DMD is rapidly progressive, with affected children being wheelchair dependent by age 12 years. Cardiomyopathy occurs in almost all individuals with DMD after age 18 years. Few survive beyond the third decade, with respiratory complications and progressive cardiomyopathy being common causes of death. Becker muscular dystrophy (BMD) is characterized by later-onset skeletal muscle weakness. With improved diagnostic techniques, it has been recognized that the mild end of the spectrum includes men with onset of symptoms after age 30 years who remain ambulatory even into their 60s. Despite the milder skeletal muscle involvement, heart failure from DCM is a common cause of morbidity and the most common cause of death in BMD. Mean age of death is in the mid-40s. DMD-associated DCM is characterized by left ventricular dilation and congestive heart failure. Females heterozygous for a DMD pathogenic variant are at increased risk for DCM.
Glycogen storage disease, type II
MedGen UID:
5340
Concept ID:
C0017921
Disease or Syndrome
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.
Autosomal recessive limb-girdle muscular dystrophy type 2F
MedGen UID:
331308
Concept ID:
C1832525
Disease or Syndrome
Autosomal recessive limb-girdle muscular dystrophy-6 (LGMDR6) is a very rare and severe neuromuscular disorder with onset in most patients in the first decade of life. Generalized muscle weakness affecting predominantly proximal and distal muscles of the limbs is progressive, and patients require walking aids or become wheelchair-bound. Some patients have cardiomyopathy or heart rhythm abnormalities, or require ventilatory support (Alonso-Perez et al., 2022). For a discussion of genetic heterogeneity of autosomal recessive limb-girdle muscular dystrophy, see LGMDR1 (253600).
Myofibrillar myopathy 5
MedGen UID:
372186
Concept ID:
C1836050
Disease or Syndrome
Other signs and symptoms of myofibrillar myopathy can include a weakened heart muscle (cardiomyopathy), muscle pain (myalgia), loss of sensation and weakness in the limbs (peripheral neuropathy), and respiratory failure. Individuals with this condition may have skeletal problems including joint stiffness (contractures) and abnormal side-to-side curvature of the spine (scoliosis). Rarely, people with this condition develop clouding of the lens of the eyes (cataracts).\n\nThe signs and symptoms of myofibrillar myopathy vary widely among affected individuals, typically depending on the condition's genetic cause. Most people with this disorder begin to develop muscle weakness (myopathy) in mid-adulthood. However, features of this condition can appear anytime between infancy and late adulthood. Muscle weakness most often begins in the hands and feet (distal muscles), but some people first experience weakness in the muscles near the center of the body (proximal muscles). Other affected individuals develop muscle weakness throughout their body. Facial muscle weakness can cause swallowing and speech difficulties. Muscle weakness worsens over time.\n\nMyofibrillar myopathy is part of a group of disorders called muscular dystrophies that affect muscle function and cause weakness. Myofibrillar myopathy primarily affects skeletal muscles, which are muscles that the body uses for movement. In some cases, the heart (cardiac) muscle is also affected.
Autosomal recessive limb-girdle muscular dystrophy type 2K
MedGen UID:
332193
Concept ID:
C1836373
Disease or Syndrome
Limb-girdle muscular dystrophies resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239) represent the mildest end of the phenotypic spectrum of muscular dystrophies collectively known as dystroglycanopathies. The limb-girdle phenotype is characterized by onset of muscular weakness apparent after ambulation is achieved; mental retardation and mild brain anomalies are variable (Balci et al., 2005; review by Godfrey et al., 2007). The most severe end of the phenotypic spectrum of dystroglycanopathies is represented by congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A; see MDDGA1, 236670), previously designated Walker-Warburg syndrome (WWS) or muscle-eye-brain disease (MEB), and the intermediate range of the spectrum is represented by congenital muscular dystrophy-dystroglycanopathy with or without mental retardation (type B; see MDDGB1, 613155). Genetic Heterogeneity of Limb-Girdle Muscular Dystrophy-Dystroglycanopathy (Type C) Limb-girdle muscular dystrophy due to defective glycosylation of DAG1 is genetically heterogeneous. See also MDDGC2 (613158), caused by mutation in the POMT2 gene (607439); MDDGC3 (613157), caused by mutation in the POMGNT1 gene (606822); MDDGC4 (611588), caused by mutation in the FKTN gene (607440); MDDGC5 (607155), caused by mutation in the FKRP gene (606596); MDDGC7 (616052), caused by mutation in the ISPD gene (CRPPA; 614631); MDDGC8 (618135), caused by mutation in the POMGNT2 gene (614828); MDDGC9 (613818) caused by mutation in the DAG1 gene (128239); MDDGC12 (616094), caused by mutation in the POMK gene (615247); MDDGC14 (615352) caused by mutation in the GMPPB gene (615320); and MDDGC15 (612937), caused by mutation in the DPM3 gene (605951).
Nemaline myopathy 6
MedGen UID:
373095
Concept ID:
C1836472
Disease or Syndrome
Nemaline myopathy-6 is an autosomal dominant skeletal muscle disorder characterized by childhood onset of slowly progressive proximal muscle weakness, exercise intolerance, and slow movements with stiff muscles. Patients are unable to run or correct themselves from falling over. Histopathologic changes seen on skeletal muscle biopsy include nemaline rods, cores devoid of oxidative enzyme activity, and predominance of hypertrophic type 1 fibers. There is no cardiac or respiratory involvement (summary by Sambuughin et al., 2010).
Autosomal recessive limb-girdle muscular dystrophy type 2J
MedGen UID:
324741
Concept ID:
C1837342
Disease or Syndrome
A form of limb-girdle muscular dystrophy that usually has a childhood onset (but can range from the first to third decade of life) of severe progressive proximal weakness, eventually involving the distal muscles. Some patients may remain ambulatory but most are wheelchair dependant 20 years after onset. Caused by homozygous mutation in the titin gene (TTN).
X-linked myopathy with excessive autophagy
MedGen UID:
374264
Concept ID:
C1839615
Disease or Syndrome
X-linked myopathy with excessive autophagy (XMEA) is an X-linked recessive skeletal muscle disorder characterized by childhood onset of progressive muscle weakness and atrophy primarily affecting the proximal muscles. While onset is usually in childhood, it can range from infancy to adulthood. Many patients lose ambulation and become wheelchair-bound. Other organ systems, including the heart, are clinically unaffected. Muscle biopsy shows intracytoplasmic autophagic vacuoles with sarcolemmal features and a multilayered basal membrane (summary by Ramachandran et al., 2013; Kurashige et al., 2013, and Ruggieri et al., 2015). Danon disease (300257), caused by mutation in the LAMP2 gene (309060) on chromosome Xq24, is a distinct disorder with similar pathologic features.
Autosomal dominant limb-girdle muscular dystrophy type 1F
MedGen UID:
333983
Concept ID:
C1842062
Disease or Syndrome
Autosomal dominant limb-girdle muscular dystrophy-2 (LGMDD2) is a myopathy characterized by proximal muscle weakness primarily affecting the lower limbs, but also affecting the upper limbs in most patients. Affected individuals also have distal muscle weakness of the hands and lower leg muscles. There is variability in presentation and progression. Some patients present in early childhood with mildly delayed walking and difficulty running and jumping, whereas others present as adults with mainly pelvic-girdle weakness. Patients with early onset tend to have a more severe disorder, and may develop contractures, loss of independent ambulation, and respiratory insufficiency. Muscle biopsy shows dystrophic changes with abnormal nuclei, rimmed vacuoles, and filamentous inclusions (summary by Melia et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of autosomal dominant limb-girdle muscular dystrophy, see LGMDD1 (603511).
Myosin storage myopathy
MedGen UID:
374868
Concept ID:
C1842160
Disease or Syndrome
Autosomal dominant myosin storage congenital myopathy-7A (CMYP7A) is a skeletal muscle disorder with wide phenotypic variability. The age at symptom onset can range from early childhood to late adulthood. Affected individuals have proximal muscle weakness affecting the upper and lower limbs and distal muscle weakness of the lower limbs, resulting in gait difficulties and scapular winging (scapuloperoneal myopathy). Additional features may include thin habitus, high-arched palate, foot drop, pes cavus, calf pseudohypertrophy, and decreased reflexes. The severity is also variable: some patients develop respiratory insufficiency, joint contractures, and scoliosis in the first decades, whereas others are clinically unaffected, but show subtle signs of the disorder on examination. Serum creatine kinase may be normal or elevated. The disease is usually slowly progressive and most patients remain ambulatory. Skeletal muscle biopsy can show different abnormalities, including hyaline bodies, type 1 fiber predominance, congenital fiber-type disproportion (CFTD), and nonspecific myopathic changes with myofibrillar disarray. Intrafamilial variability is common (Dye et al., 2006; Pegoraro et al., 2007; review by Tajsharghi and Oldfors, 2013). For a discussion of genetic heterogeneity of congenital myopathy, see CMYP1A (117000).
Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis
MedGen UID:
375302
Concept ID:
C1843851
Disease or Syndrome
POLG-related disorders comprise a continuum of overlapping phenotypes that were clinically defined long before their molecular basis was known. Most affected individuals have some, but not all, of the features of a given phenotype; nonetheless, the following nomenclature can assist the clinician in diagnosis and management. Onset of the POLG-related disorders ranges from infancy to late adulthood. Alpers-Huttenlocher syndrome (AHS), one of the most severe phenotypes, is characterized by childhood-onset progressive and ultimately severe encephalopathy with intractable epilepsy and hepatic failure. Childhood myocerebrohepatopathy spectrum (MCHS) presents between the first few months of life and about age three years with developmental delay or dementia, lactic acidosis, and a myopathy with failure to thrive. Other findings can include liver failure, renal tubular acidosis, pancreatitis, cyclic vomiting, and hearing loss. Myoclonic epilepsy myopathy sensory ataxia (MEMSA) now describes the spectrum of disorders with epilepsy, myopathy, and ataxia without ophthalmoplegia. MEMSA now includes the disorders previously described as spinocerebellar ataxia with epilepsy (SCAE). The ataxia neuropathy spectrum (ANS) includes the phenotypes previously referred to as mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO). About 90% of persons in the ANS have ataxia and neuropathy as core features. Approximately two thirds develop seizures and almost one half develop ophthalmoplegia; clinical myopathy is rare. Autosomal recessive progressive external ophthalmoplegia (arPEO) is characterized by progressive weakness of the extraocular eye muscles resulting in ptosis and ophthalmoparesis (or paresis of the extraocular muscles) without associated systemic involvement; however, caution is advised because many individuals with apparently isolated arPEO at the onset develop other manifestations of POLG-related disorders over years or decades. Of note, in the ANS spectrum the neuropathy commonly precedes the onset of PEO by years to decades. Autosomal dominant progressive external ophthalmoplegia (adPEO) typically includes a generalized myopathy and often variable degrees of sensorineural hearing loss, axonal neuropathy, ataxia, depression, parkinsonism, hypogonadism, and cataracts (in what has been called "chronic progressive external ophthalmoplegia plus," or "CPEO+").
Autosomal recessive limb-girdle muscular dystrophy type 2I
MedGen UID:
339580
Concept ID:
C1846672
Disease or Syndrome
MDGDC5 is an autosomal recessive muscular dystrophy characterized by variable age at onset, normal cognition, and no structural brain changes (Brockington et al., 2001). It is part of a group of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (Mercuri et al., 2006). For a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type C, see MDDGC1 (609308).
Muscular dystrophy-dystroglycanopathy type B5
MedGen UID:
335764
Concept ID:
C1847759
Disease or Syndrome
MDDGB5 is an autosomal recessive congenital muscular dystrophy with impaired intellectual development and structural brain abnormalities (Brockington et al., 2001). It is part of a group of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (Mercuri et al., 2006). For a discussion of genetic heterogeneity of congenital muscular dystrophy-dystroglycanopathy type B, see MDDGB1 (613155).
Autosomal recessive limb-girdle muscular dystrophy type 2B
MedGen UID:
338149
Concept ID:
C1850889
Disease or Syndrome
Dysferlinopathy includes a spectrum of muscle disease characterized by two major phenotypes: Miyoshi muscular dystrophy (MMD) and limb-girdle muscular dystrophy type 2B (LGMD2B); and two minor phenotypes: asymptomatic hyperCKemia and distal myopathy with anterior tibial onset (DMAT). MMD (median age of onset 19 years) is characterized by muscle weakness and atrophy, most marked in the distal parts of the legs, especially the gastrocnemius and soleus muscles. Over a period of years, the weakness and atrophy spread to the thighs and gluteal muscles. The forearms may become mildly atrophic with decrease in grip strength; the small muscles of the hands are spared. LGMD2B is characterized by early weakness and atrophy of the pelvic and shoulder girdle muscles in adolescence or young adulthood, with slow progression. Other phenotypes in this spectrum are scapuloperoneal syndrome and congenital muscular dystrophy. Asymptomatic hyperCKemia is characterized by marked elevation of serum CK concentration only. DMAT is characterized by early and predominant distal muscle weakness, particularly of the muscles of the anterior compartment of the legs.
Microcephaly 2, primary, autosomal recessive, with or without cortical malformations
MedGen UID:
346929
Concept ID:
C1858535
Disease or Syndrome
In WDR62 primary microcephaly (WDR62-MCPH), microcephaly (occipitofrontal circumference [OFC] = -2 SD) is usually present at birth, but in some instances becomes evident later in the first year of life. Growth is otherwise normal. Except for brain malformations in most affected individuals, no other congenital malformations are observed. Central nervous system involvement can include delayed motor development, mild-to-severe intellectual disability (ID), behavior problems, epilepsy, spasticity, and ataxia.
Autosomal recessive limb-girdle muscular dystrophy type 2G
MedGen UID:
400895
Concept ID:
C1866008
Disease or Syndrome
A mild form of limb-girdle muscular dystrophy with characteristics of muscle weakness in the four limbs, mild scapular winging, severe atrophy of the quadriceps and anterior tibialis muscles, calf hypertrophy and lack of respiratory and cardiac involvement.
Neuronopathy, distal hereditary motor, autosomal recessive 4
MedGen UID:
369682
Concept ID:
C1970211
Disease or Syndrome
A rare genetic neuromuscular disease characterized by proximal muscle weakness with an early involvement of foot and hand muscles following normal motor development in early childhood, a rapidly progressive disease course leading to generalized areflexic tetraplegia with contractures, severe scoliosis, hyperlordosis, and progressive respiratory insufficiency leading to assisted ventilation. Cranial nerve functions are normal and tongue wasting and fasciculations are absent. Milder phenotype with a moderate generalized weakness and slower disease progress was reported. There is evidence the disease is caused by homozygous mutation in the gene encoding pleckstrin homology domain-containing protein, family G member 5 (PLEKHG5) on chromosome 1p36.
Early-onset myopathy with fatal cardiomyopathy
MedGen UID:
435983
Concept ID:
C2673677
Disease or Syndrome
Salih myopathy is characterized by muscle weakness (manifest during the neonatal period or in early infancy) and delayed motor development; children acquire independent walking between ages 20 months and four years. In the first decade of life, global motor performance is stable or tends to improve. Moderate joint and neck contractures and spinal rigidity may manifest in the first decade but become more obvious in the second decade. Scoliosis develops after age 11 years. Cardiac dysfunction manifests between ages five and 16 years, progresses rapidly, and leads to death between ages eight and 20 years, usually from heart rhythm disturbances.
Miyoshi muscular dystrophy 3
MedGen UID:
413750
Concept ID:
C2750076
Disease or Syndrome
The spectrum of ANO5 muscle disease is a continuum that ranges from asymptomatic hyperCKemia and exercise-induced myalgia to proximal and/or distal muscle weakness. The most typical presentation is limb-girdle muscular dystrophy type 2L (LGMD2L) with late-onset proximal lower-limb weakness in the fourth or fifth decade (range 15-70 years). Less common is Miyoshi-like disease (Miyoshi muscular dystrophy 3) with early-adult-onset calf distal myopathy (around age 20 years). Incidental hyperCKemia may be present even earlier. Initial symptoms are walking difficulties, reduced sports performance, and difficulties in standing on toes as well as nonspecific exercise myalgia and/or burning sensation in the calf muscles. Muscle weakness and atrophy are frequently asymmetric. Cardiac findings can include cardiomyopathy and arrhythmias and/or left ventricular dysfunction. Bulbar or respiratory symptoms have not been reported. Females have milder disease manifestations than males. Disease progression is slow in both the LGMD and distal forms; ambulation is preserved until very late in the disease course. Life span is normal.
Autosomal recessive limb-girdle muscular dystrophy type 2O
MedGen UID:
461767
Concept ID:
C3150417
Disease or Syndrome
MDDGC3 is a rare form of autosomal recessive limb-girdle muscular dystrophy with normal cognition (Clement et al., 2008). It is part of a group of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1; 128239), collectively known as 'dystroglycanopathies' (Godfrey et al., 2007). For a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type C, see MDDGC1 (609308).
Autosomal recessive limb-girdle muscular dystrophy type 2Q
MedGen UID:
462339
Concept ID:
C3150989
Disease or Syndrome
Autosomal recessive limb-girdle muscular dystrophy-17 (LGMDR17) is characterized by early childhood onset of proximal muscle weakness and atrophy without skin involvement. One family has shown rapid progression of the disorder in adolescence (summary by Gundesli et al., 2010). For a discussion of genetic heterogeneity of autosomal recessive limb-girdle muscular dystrophy, see LGMDR1 (253600).
Congenital myopathy 10b, mild variant
MedGen UID:
762102
Concept ID:
C3541476
Disease or Syndrome
Congenital myopathy-10B (CMYP10B) is an autosomal recessive skeletal muscle disorder characterized by infantile- or childhood-onset myopathy, areflexia, dysphagia, and respiratory distress that usually requires nocturnal ventilation. Other common features include facial and neck muscle weakness, feeding difficulties, contractures, scoliosis, high-arched palate, hyporeflexia, and difficulties walking. The disorder is slowly progressive and most patients follow a chronic course. Muscle biopsy shows variable findings, including type 1 fiber predominance, minicore lesions, and myofibrillar disorganization (Boyden et al., 2012; Harris et al., 2018). Patients with missense mutations affecting conserved cysteine residues in the EGF-like domain show the mild variant phenotype (CMYP10B) with later onset of respiratory failure and minicores on muscle biopsy, whereas patients with more damaging mutations, including nonsense or frameshift null mutations, show the severe variant phenotype (CMYP10A) (Croci et al., 2022). For a discussion of genetic heterogeneity of congenital myopathy, see CMYP1A (117000).
Mitochondrial DNA deletion syndrome with progressive myopathy
MedGen UID:
767513
Concept ID:
C3554599
Disease or Syndrome
PEOA6 is characterized by muscle weakness, mainly affecting the lower limbs, external ophthalmoplegia, exercise intolerance, and mitochondrial DNA (mtDNA) deletions on muscle biopsy. Symptoms may appear in childhood or adulthood and show slow progression (summary by Ronchi et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant progressive external ophthalmoplegia, see PEOA1 (157640).
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14
MedGen UID:
815546
Concept ID:
C3809216
Disease or Syndrome
LIPE-related familial partial lipodystrophy
MedGen UID:
863306
Concept ID:
C4014869
Disease or Syndrome
Familial partial lipodystrophy type 6 (FPLD6) is characterized by abnormal subcutaneous fat distribution, with variable excess accumulation of fat in the face, neck, shoulders, axillae, back, abdomen, and pubic region, and reduction in subcutaneous fat of the lower extremities. Progressive adult-onset myopathy is seen in some patients, and there is variable association with diabetes, hypertriglyceridemia, low high-density lipoprotein (HDL) cholesterol, and hepatic steatosis (Zolotov et al., 2017). For a general phenotypic description and a discussion of genetic heterogeneity of familial partial lipodystrophy (FPLD), see 151660.
Limb-girdle muscular dystrophy due to POMK deficiency
MedGen UID:
863621
Concept ID:
C4015184
Disease or Syndrome
A form of limb-girdle muscular dystrophy presenting in infancy with muscle weakness and delayed motor development (eventually learning to walk at 18 months of age) followed by progressive proximal weakness, pseudohypertrophy of calf muscles, mild facial weakness and borderline intelligence.
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1
MedGen UID:
897191
Concept ID:
C4225153
Disease or Syndrome
POLG-related disorders comprise a continuum of overlapping phenotypes that were clinically defined long before their molecular basis was known. Most affected individuals have some, but not all, of the features of a given phenotype; nonetheless, the following nomenclature can assist the clinician in diagnosis and management. Onset of the POLG-related disorders ranges from infancy to late adulthood. Alpers-Huttenlocher syndrome (AHS), one of the most severe phenotypes, is characterized by childhood-onset progressive and ultimately severe encephalopathy with intractable epilepsy and hepatic failure. Childhood myocerebrohepatopathy spectrum (MCHS) presents between the first few months of life and about age three years with developmental delay or dementia, lactic acidosis, and a myopathy with failure to thrive. Other findings can include liver failure, renal tubular acidosis, pancreatitis, cyclic vomiting, and hearing loss. Myoclonic epilepsy myopathy sensory ataxia (MEMSA) now describes the spectrum of disorders with epilepsy, myopathy, and ataxia without ophthalmoplegia. MEMSA now includes the disorders previously described as spinocerebellar ataxia with epilepsy (SCAE). The ataxia neuropathy spectrum (ANS) includes the phenotypes previously referred to as mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO). About 90% of persons in the ANS have ataxia and neuropathy as core features. Approximately two thirds develop seizures and almost one half develop ophthalmoplegia; clinical myopathy is rare. Autosomal recessive progressive external ophthalmoplegia (arPEO) is characterized by progressive weakness of the extraocular eye muscles resulting in ptosis and ophthalmoparesis (or paresis of the extraocular muscles) without associated systemic involvement; however, caution is advised because many individuals with apparently isolated arPEO at the onset develop other manifestations of POLG-related disorders over years or decades. Of note, in the ANS spectrum the neuropathy commonly precedes the onset of PEO by years to decades. Autosomal dominant progressive external ophthalmoplegia (adPEO) typically includes a generalized myopathy and often variable degrees of sensorineural hearing loss, axonal neuropathy, ataxia, depression, parkinsonism, hypogonadism, and cataracts (in what has been called "chronic progressive external ophthalmoplegia plus," or "CPEO+").
Myofibrillar myopathy 8
MedGen UID:
934612
Concept ID:
C4310645
Disease or Syndrome
Myofibrillar myopathy-8 (MFM8) is an autosomal recessive myopathy characterized by slowly progressive proximal muscle weakness and atrophy affecting the upper and lower limbs, resulting in increased falls, gait problems, difficulty running or climbing stairs, and upper limb weakness or scapular winging. Some patients develop distal muscle weakness and atrophy. The phenotype may also be consistent with a clinical diagnosis of limb-girdle muscular dystrophy (LGMD). Age at symptom onset ranges from infancy to adulthood. Ambulation is generally preserved and cardiac involvement is rare, but respiratory compromise with decreased forced vital capacity often occurs. Muscle biopsy shows a mix of myopathic features, including myofibrillar inclusions and sarcomeric disorganization; some patients have been reported to have dystrophic changes on muscle biopsy (O'Grady et al., 2016; Daimaguler et al., 2021). There is significant phenotypic variation, even in patients with the same mutation, which must be taken into account when counseling affecting individuals (Woods et al., 2020). For a general phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy, see MFM1 (601419).
Autosomal recessive limb-girdle muscular dystrophy type 2Y
MedGen UID:
1385152
Concept ID:
C4511482
Disease or Syndrome
Autosomal recessive myopathy with rigid spine and distal joint contractures (MRRSDC) is characterized by onset of slowly progressive muscle weakness in the first or second decades of life. There is initial involvement of the proximal lower limbs, followed by distal upper and lower limb muscle weakness and atrophy. Other features include joint contractures, rigid spine, and restricted pulmonary function; some patients may have mild cardiac involvement (summary by Kayman-Kurekci et al., 2014).
Autosomal recessive limb-girdle muscular dystrophy type 2P
MedGen UID:
1386785
Concept ID:
C4511963
Disease or Syndrome
MDDGC9 is an autosomal recessive muscular dystrophy showing onset in early childhood. It is part of a group of similar disorders resulting from defective glycosylation of DAG1, collectively known as 'dystroglycanopathies' (summary by Hara et al., 2011). For a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type C, see MDDGC1 (609308).
Inclusion body myopathy with Paget disease of bone and frontotemporal dementia type 1
MedGen UID:
1641069
Concept ID:
C4551951
Disease or Syndrome
Inclusion body myopathy associated with Paget disease of bone (PDB) and/or frontotemporal dementia (IBMPFD) is characterized by adult-onset proximal and distal muscle weakness (clinically resembling a limb-girdle muscular dystrophy syndrome), early-onset PDB, and premature frontotemporal dementia (FTD). Muscle weakness progresses to involve other limb and respiratory muscles. PDB involves focal areas of increased bone turnover that typically lead to spine and/or hip pain and localized enlargement and deformity of the long bones; pathologic fractures occur on occasion. Early stages of FTD are characterized by dysnomia, dyscalculia, comprehension deficits, and paraphasic errors, with minimal impairment of episodic memory; later stages are characterized by inability to speak, auditory comprehension deficits for even one-step commands, alexia, and agraphia. Mean age at diagnosis for muscle disease and PDB is 42 years; for FTD, 56 years. Dilated cardiomyopathy, amyotrophic lateral sclerosis, and Parkinson disease are now known to be part of the spectrum of findings associated with IBMPFD.
Miyoshi muscular dystrophy 1
MedGen UID:
1640757
Concept ID:
C4551973
Disease or Syndrome
Dysferlinopathy includes a spectrum of muscle disease characterized by two major phenotypes: Miyoshi muscular dystrophy (MMD) and limb-girdle muscular dystrophy type 2B (LGMD2B); and two minor phenotypes: asymptomatic hyperCKemia and distal myopathy with anterior tibial onset (DMAT). MMD (median age of onset 19 years) is characterized by muscle weakness and atrophy, most marked in the distal parts of the legs, especially the gastrocnemius and soleus muscles. Over a period of years, the weakness and atrophy spread to the thighs and gluteal muscles. The forearms may become mildly atrophic with decrease in grip strength; the small muscles of the hands are spared. LGMD2B is characterized by early weakness and atrophy of the pelvic and shoulder girdle muscles in adolescence or young adulthood, with slow progression. Other phenotypes in this spectrum are scapuloperoneal syndrome and congenital muscular dystrophy. Asymptomatic hyperCKemia is characterized by marked elevation of serum CK concentration only. DMAT is characterized by early and predominant distal muscle weakness, particularly of the muscles of the anterior compartment of the legs.
Autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)
MedGen UID:
1648441
Concept ID:
C4721885
Disease or Syndrome
Autosomal dominant limb-girdle muscular dystrophy is characterized by proximal and/or distal muscle weakness and atrophy. The age at onset is variable and can range from the first to the sixth decade, although later onset is less common. Most patients present with proximal muscle weakness that progresses to distal involvement, but some can present with distal impairment. The severity is variable: patients with a more severe phenotype can lose ambulation after several decades and have facial weakness with bulbar and respiratory involvement. Muscle biopsy shows dystrophic changes with protein aggregates, myofibrillar degeneration, and rimmed vacuoles (summary by Ruggieri et al., 2015). Genetic Heterogeneity of Autosomal Dominant Limb-Girdle Muscular Dystrophy Other forms of autosomal dominant LGMD include LGMDD2 (608423), previously LGMD1F, caused by mutation in the TNPO3 gene (610032) on chromosome 7q32; LGMDD3 (609115), previously LGMD1G, caused by mutation in the HNRNPDL gene (607137) on chromosome 4q21; and LGMDD4 (618129), previously LGMD1I, caused by mutation in the CAPN3 gene (114240) on chromosome 15q15. For a discussion of autosomal recessive LGMD, see 253600.
Muscular dystrophy, limb-girdle, autosomal recessive 23
MedGen UID:
1648462
Concept ID:
C4748327
Disease or Syndrome
The clinical manifestations of LAMA2 muscular dystrophy (LAMA2-MD) comprise a continuous spectrum ranging from severe congenital muscular dystrophy type 1A (MDC1A) to milder late-onset LAMA2-MD. MDC1A is typically characterized by neonatal profound hypotonia, poor spontaneous movements, and respiratory failure. Failure to thrive, gastroesophageal reflux, aspiration, and recurrent chest infections necessitating frequent hospitalizations are common. As disease progresses, facial muscle weakness, temporomandibular joint contractures, and macroglossia may further impair feeding and can affect speech. In late-onset LAMA2-MD onset of manifestations range from early childhood to adulthood. Affected individuals may show muscle hypertrophy and develop a rigid spine syndrome with joint contractures, usually most prominent in the elbows. Progressive respiratory insufficiency, scoliosis, and cardiomyopathy can occur.
Combined oxidative phosphorylation deficiency 49
MedGen UID:
1762338
Concept ID:
C5436616
Disease or Syndrome
Facioscapulohumeral muscular dystrophy 3, digenic
MedGen UID:
1794169
Concept ID:
C5561959
Disease or Syndrome
Facioscapulohumeral muscular dystrophy-3 (FSHD3) is a digenic muscle disorder characterized by adult onset of proximal muscle weakness affecting the face, neck, scapular muscles, and upper and lower limbs. Muscle involvement is usually asymmetric, and other muscle groups may become involved with progression of the disease (summary by Hamanaka et al., 2020). For a discussion of genetic heterogeneity of FSHD, see FSHD1 (158900).
Congenital myopathy 20
MedGen UID:
1841029
Concept ID:
C5830393
Disease or Syndrome
Congenital myopathy-20 (CMYP20) is an autosomal recessive neuromuscular disorder that shows wide phenotypic variability. Some patients present in early childhood with proximal muscle weakness affecting the lower and upper limbs resulting in difficulties running and climbing, whereas others present soon after birth with congenital limb or distal contractures. Additional features may include dysmorphic facial features and global developmental delay. Skeletal muscle biopsy may show nemaline rods (Nilipour et al., 2018; Pehlivan et al., 2019). For a discussion of genetic heterogeneity of congenital myopathy, see CMYP1A (117000).
Nemaline myopathy 5B, autosomal recessive, childhood-onset
MedGen UID:
1841181
Concept ID:
C5830545
Disease or Syndrome
Autosomal recessive childhood-onset nemaline myopathy-5B (NEM5B) is a skeletal muscle disorder in which patients usually present with proximal muscle weakness of the lower and upper limbs in a limb-girdle distribution, resulting in gait abnormalities; however, most remain ambulatory even into late adulthood. Some affected individuals show delayed motor development. There is axial weakness and atrophy of the paraspinal muscles, along with kyphosis, scoliosis, and rigid spine, as well as variable limitations of the large joints. Most patients develop restrictive respiratory insufficiency with decreased forced vital capacity; some need noninvasive ventilation. Serum creatine kinase may be elevated. Muscle biopsy can show variable features, including nemaline rods, multiminicore lesions, endomysial fibrosis, and myofibrillar changes (Pellerin et al., 2020; Lee et al., 2022). For a discussion of genetic heterogeneity of nemaline myopathy, see NEM2 (256030).
Nemaline myopathy 5C, autosomal dominant
MedGen UID:
1841185
Concept ID:
C5830549
Disease or Syndrome
Autosomal dominant nemaline myopathy-5C (NEM5C) is a relatively mild skeletal muscle disorder with wide clinical variability, even within families. Affected individuals develop symptoms of muscle weakness in the first or second decades; those with earlier onset tend to have a more severe disease course. Features include difficulty walking on the heels, waddling gait, proximal muscle weakness affecting the upper and lower limbs, and Gowers sign. Additional features may include myopathic facies, high-arched palate, scoliosis or kyphosis, and ankle weakness. Patients remain ambulatory into late adulthood. Skeletal muscle biopsy shows hypotrophy of type 1 fibers, hypertrophy of type 2 fibers, fiber size variation, and myofibrillar disorganization. Nemaline rods in type 1 fibers are often observed, but are not always present (Konersman et al., 2017; Holling et al., 2022). For a discussion of genetic heterogeneity of nemaline myopathy, see NEM2 (256030).

Professional guidelines

PubMed

Ramer S, Nguyen AT, Nelson JM, Whiteman MK, Warner L, Thierry JM, Folger S, von Essen BS, Kortsmit K
Am J Public Health 2024 Jan;114(1):108-117. doi: 10.2105/AJPH.2023.307438. PMID: 38091565Free PMC Article
Al Kaissi A, Kenis V, Jemaa LB, Sassi H, Shboul M, Grill F, Ganger R, Kircher SG
Clin Rheumatol 2020 Feb;39(2):553-560. Epub 2019 Oct 18 doi: 10.1007/s10067-019-04783-z. PMID: 31628567
Kritchevsky SB, Nicklas BJ, Visser M, Simonsick EM, Newman AB, Harris TB, Lange EM, Penninx BW, Goodpaster BH, Satterfield S, Colbert LH, Rubin SM, Pahor M
JAMA 2005 Aug 10;294(6):691-8. doi: 10.1001/jama.294.6.691. PMID: 16091571

Recent clinical studies

Etiology

Salvador C, Rodrigues AM, Henriques AR, Gregório MJ, Canhão H, Mendonça N
BMC Geriatr 2022 Aug 19;22(1):687. doi: 10.1186/s12877-022-03381-0. PMID: 35986235Free PMC Article
Rustagi AS, Byers AL, Keyhani S
JAMA Netw Open 2022 Mar 1;5(3):e225318. doi: 10.1001/jamanetworkopen.2022.5318. PMID: 35357450Free PMC Article
Teresi JA, Ocepek-Welikson K, Ramirez M, Kleinman M, Wang C, Weiss DJ, Cheville A
Arch Phys Med Rehabil 2022 May;103(5S):S84-S107.e38. Epub 2021 Jun 16 doi: 10.1016/j.apmr.2021.03.044. PMID: 34146534Free PMC Article
Barry LC, Coman E, Wakefield D, Trestman RL, Conwell Y, Steffens DC
J Affect Disord 2020 Apr 1;266:366-373. Epub 2020 Jan 30 doi: 10.1016/j.jad.2020.01.156. PMID: 32056900Free PMC Article
Streicher M, van Zwienen-Pot J, Bardon L, Nagel G, Teh R, Meisinger C, Colombo M, Torbahn G, Kiesswetter E, Flechtner-Mors M, Denkinger M, Rothenbacher D, Thorand B, Ladwig KH, Corish CA, Clarke M, Kerse N, Muru-Lanning M, Gibney ER, O'Connor EM, Visser M, Volkert D; MaNuEL consortium
J Am Geriatr Soc 2018 Dec;66(12):2335-2343. Epub 2018 Aug 23 doi: 10.1111/jgs.15553. PMID: 30136728

Diagnosis

Lima AB, Baptista F, Henrinques-Neto D, Pinto AA, Gouveia ER
Int J Environ Res Public Health 2023 Feb 3;20(3) doi: 10.3390/ijerph20032711. PMID: 36768077Free PMC Article
Tsang M, Gan S, Boscardin WJ, Wong ML, Walter LC, Smith AK
J Am Geriatr Soc 2022 Dec;70(12):3402-3412. Epub 2022 Oct 19 doi: 10.1111/jgs.18039. PMID: 36259424Free PMC Article
Engvall K, Gréen H, Fredrikson M, Lagerlund M, Lewin F, Åvall-Lundqvist E
Breast Cancer Res Treat 2022 Oct;195(3):379-391. Epub 2022 Aug 9 doi: 10.1007/s10549-022-06670-9. PMID: 35941422Free PMC Article
Teresi JA, Ocepek-Welikson K, Ramirez M, Kleinman M, Wang C, Weiss DJ, Cheville A
Arch Phys Med Rehabil 2022 May;103(5S):S84-S107.e38. Epub 2021 Jun 16 doi: 10.1016/j.apmr.2021.03.044. PMID: 34146534Free PMC Article
Fettes L, Bone AE, Etkind SN, Ashford S, Higginson IJ, Maddocks M
J Pain Symptom Manage 2021 Jun;61(6):1205-1214. Epub 2020 Oct 21 doi: 10.1016/j.jpainsymman.2020.10.012. PMID: 33096219

Therapy

Engvall K, Gréen H, Fredrikson M, Lagerlund M, Lewin F, Åvall-Lundqvist E
Breast Cancer Res Treat 2022 Oct;195(3):379-391. Epub 2022 Aug 9 doi: 10.1007/s10549-022-06670-9. PMID: 35941422Free PMC Article
Mendonça N, Hengeveld LM, Visser M, Presse N, Canhão H, Simonsick EM, Kritchevsky SB, Newman AB, Gaudreau P, Jagger C
Am J Clin Nutr 2021 Jul 1;114(1):29-41. doi: 10.1093/ajcn/nqab051. PMID: 33829238Free PMC Article
Streicher M, van Zwienen-Pot J, Bardon L, Nagel G, Teh R, Meisinger C, Colombo M, Torbahn G, Kiesswetter E, Flechtner-Mors M, Denkinger M, Rothenbacher D, Thorand B, Ladwig KH, Corish CA, Clarke M, Kerse N, Muru-Lanning M, Gibney ER, O'Connor EM, Visser M, Volkert D; MaNuEL consortium
J Am Geriatr Soc 2018 Dec;66(12):2335-2343. Epub 2018 Aug 23 doi: 10.1111/jgs.15553. PMID: 30136728
Sharma N, Cooper R, Kuh D, Shah I
Sci Rep 2017 Jul 26;7(1):6578. doi: 10.1038/s41598-017-06019-z. PMID: 28747665Free PMC Article
Alexander D, Allardice GM, Moug SJ, Morrison DS
Colorectal Dis 2017 Jun;19(6):544-550. doi: 10.1111/codi.13594. PMID: 28027419

Prognosis

Tsang M, Gan S, Boscardin WJ, Wong ML, Walter LC, Smith AK
J Am Geriatr Soc 2022 Dec;70(12):3402-3412. Epub 2022 Oct 19 doi: 10.1111/jgs.18039. PMID: 36259424Free PMC Article
Iskandar K, Sunartini, Astari FN, Gumilang RA, Ilma N, Shartyanie NP, Adistyawan G, Tan G, Gunadi, Lai PS
BMC Pediatr 2022 Oct 17;22(1):601. doi: 10.1186/s12887-022-03662-y. PMID: 36253810Free PMC Article
Streicher M, van Zwienen-Pot J, Bardon L, Nagel G, Teh R, Meisinger C, Colombo M, Torbahn G, Kiesswetter E, Flechtner-Mors M, Denkinger M, Rothenbacher D, Thorand B, Ladwig KH, Corish CA, Clarke M, Kerse N, Muru-Lanning M, Gibney ER, O'Connor EM, Visser M, Volkert D; MaNuEL consortium
J Am Geriatr Soc 2018 Dec;66(12):2335-2343. Epub 2018 Aug 23 doi: 10.1111/jgs.15553. PMID: 30136728
Alexander D, Allardice GM, Moug SJ, Morrison DS
Colorectal Dis 2017 Jun;19(6):544-550. doi: 10.1111/codi.13594. PMID: 28027419
Węgrzynowska-Teodorczyk K, Mozdzanowska D, Josiak K, Siennicka A, Nowakowska K, Banasiak W, Jankowska EA, Ponikowski P, Woźniewski M
Eur J Prev Cardiol 2016 Aug;23(12):1307-13. Epub 2016 Jan 7 doi: 10.1177/2047487315625235. PMID: 26743588

Clinical prediction guides

Tsang M, Gan S, Boscardin WJ, Wong ML, Walter LC, Smith AK
J Am Geriatr Soc 2022 Dec;70(12):3402-3412. Epub 2022 Oct 19 doi: 10.1111/jgs.18039. PMID: 36259424Free PMC Article
Salvador C, Rodrigues AM, Henriques AR, Gregório MJ, Canhão H, Mendonça N
BMC Geriatr 2022 Aug 19;22(1):687. doi: 10.1186/s12877-022-03381-0. PMID: 35986235Free PMC Article
Engvall K, Gréen H, Fredrikson M, Lagerlund M, Lewin F, Åvall-Lundqvist E
Breast Cancer Res Treat 2022 Oct;195(3):379-391. Epub 2022 Aug 9 doi: 10.1007/s10549-022-06670-9. PMID: 35941422Free PMC Article
Teresi JA, Ocepek-Welikson K, Ramirez M, Kleinman M, Wang C, Weiss DJ, Cheville A
Arch Phys Med Rehabil 2022 May;103(5S):S84-S107.e38. Epub 2021 Jun 16 doi: 10.1016/j.apmr.2021.03.044. PMID: 34146534Free PMC Article
Barry LC, Coman E, Wakefield D, Trestman RL, Conwell Y, Steffens DC
J Affect Disord 2020 Apr 1;266:366-373. Epub 2020 Jan 30 doi: 10.1016/j.jad.2020.01.156. PMID: 32056900Free PMC Article

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