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Foot dorsiflexor weakness

MedGen UID:
356163
Concept ID:
C1866141
Finding
Synonyms: Inability to walk on heels; Weakness of foot dorsiflexors
 
HPO: HP:0009027

Definition

Weakness of the muscles responsible for dorsiflexion of the foot, that is, of the movement of the toes towards the shin. The foot dorsiflexors include the tibialis anterior, the extensor hallucis longus, the extensor digitorum longus, and the peroneus tertius muscles. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVFoot dorsiflexor weakness

Conditions with this feature

Chédiak-Higashi syndrome
MedGen UID:
3347
Concept ID:
C0007965
Disease or Syndrome
Chediak-Higashi syndrome (CHS) is characterized by partial oculocutaneous albinism, immunodeficiency, and a mild bleeding tendency. Approximately 85% of affected individuals develop the accelerated phase, or hemophagocytic lymphohistiocytosis, a life-threatening, hyperinflammatory condition. All affected individuals including adolescents and adults with atypical CHS and children with classic CHS who have successfully undergone allogenic hematopoietic stem cell transplantation (HSCT) develop neurologic findings during early adulthood.
Dejerine-Sottas disease
MedGen UID:
3710
Concept ID:
C0011195
Disease or Syndrome
Dejerine-Sottas neuropathy is a demyelinating peripheral neuropathy with onset in infancy. It can show autosomal dominant or recessive inheritance. Affected individuals have delayed motor development due to severe distal motor and sensory impairment, resulting in difficulties in gait. Some patients have generalized hypotonia in infancy. Other features may include pes cavus, scoliosis, and sensory ataxia. Nerve conduction velocities are severely decreased (sometimes less than 10 m/s), and sural nerve biopsy shows severe loss of myelinated fibers (summary by Baets et al., 2011).
Pelger-Huët anomaly
MedGen UID:
10617
Concept ID:
C0030779
Disease or Syndrome
An autosomal dominant inherited condition caused by mutations in the lamin B receptor gene. It is characterized by defects in the neutrophil lobulation, resulting in the presence of dumbbell-shaped neutrophils with bilobed nuclei in the peripheral blood smear.
Charcot-Marie-Tooth disease, type IA
MedGen UID:
75727
Concept ID:
C0270911
Disease or Syndrome
For a general phenotypic description and a discussion of genetic heterogeneity of Charcot-Marie-Tooth disease type 1, see CMT1B (118200). CMT1A is the most common form of CMT. The average age of onset of clinical symptoms is 12.2 +/- 7.3 years. Slow nerve conduction velocity (NCV) less than 38 m/s is highly diagnostic and is a 100% penetrant phenotype independent of age (Lupski et al., 1991, 1992).
Charcot-Marie-Tooth disease type 1B
MedGen UID:
124377
Concept ID:
C0270912
Disease or Syndrome
Charcot-Marie-Tooth disease is a sensorineural peripheral polyneuropathy. Affecting approximately 1 in 2,500 individuals, Charcot-Marie-Tooth disease is the most common inherited disorder of the peripheral nervous system (Skre, 1974). Autosomal dominant, autosomal recessive, and X-linked forms have been recognized. Classification On the basis of electrophysiologic properties and histopathology, CMT has been divided into primary peripheral demyelinating (type 1, or HMSNI) and primary peripheral axonal (type 2, or HMSNII) neuropathies. The demyelinating neuropathies classified as CMT type 1 are characterized by severely reduced motor NCVs (less than 38 m/s) and segmental demyelination and remyelination with onion bulb formations on nerve biopsy. The axonal neuropathies classified as CMT type 2 are characterized by normal or mildly reduced NCVs and chronic axonal degeneration and regeneration on nerve biopsy (see CMT2A1; 118210). Distal hereditary motor neuropathy (dHMN) (see 158590), or spinal CMT, is characterized by exclusive motor involvement and sparing of sensory nerves (Pareyson, 1999). McAlpine (1989) proposed that the forms of CMT with very slow nerve conduction be given the gene symbol CMT1A (118220) and CMT1B, CMT1A being the gene on chromosome 17 and CMT1B being the gene on chromosome 1. CMT2 was the proposed symbol for the autosomal locus responsible for the moderately slow nerve conduction form of the disease (axonal). For a phenotypic description and discussion of genetic heterogeneity of the various subtypes of CMT, see CMTX1 (302800), CMT2A1 (118210), CMT3 (DSS; 145900), CMT4A (214400), and CMTDIB (606482). Genetic Heterogeneity of Autosomal Dominant Demyelinating CMT1 Autosomal dominant demyelinating CMT1 is a genetically heterogeneous disorder and can be caused by mutations in different genes; see CMT1A (118220), CMT1C (601098), CMT1D (607678), CMT1E (607734), CMT1F (607734), CMT1G (618279), CMT1H (619764), CMT1I (619742), and CMT1J (620111). See also 608236 for a related phenotype characterized by isolated slowed nerve conduction velocities (NCVs).
Benign scapuloperoneal muscular dystrophy with cardiomyopathy
MedGen UID:
98048
Concept ID:
C0410190
Disease or Syndrome
Emery-Dreifuss muscular dystrophy (EDMD) is characterized by the clinical triad of: joint contractures that begin in early childhood; slowly progressive muscle weakness and wasting initially in a humero-peroneal distribution that later extends to the scapular and pelvic girdle muscles; and cardiac involvement that may manifest as palpitations, presyncope and syncope, poor exercise tolerance, and congestive heart failure along with variable cardiac rhythm disturbances. Age of onset, severity, and progression of muscle and cardiac involvement demonstrate both inter- and intrafamilial variability. Clinical variability ranges from early onset with severe presentation in childhood to late onset with slow progression in adulthood. In general, joint contractures appear during the first two decades, followed by muscle weakness and wasting. Cardiac involvement usually occurs after the second decade and respiratory function may be impaired in some individuals.
Charcot-Marie-Tooth disease type 2B
MedGen UID:
371512
Concept ID:
C1833219
Disease or Syndrome
A severe form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy. Onset in the second or third decade has manifestations of ulceration and infection of the feet. Symmetric and distal weakness develops mostly in the legs together with a severe symmetric distal sensory loss. Tendon reflexes are only reduced at ankles and foot deformities including pes cavus or planus and hammer toes, appear in childhood.
Facioscapulohumeral muscular dystrophy 2
MedGen UID:
320405
Concept ID:
C1834671
Disease or Syndrome
Facioscapulohumeral muscular dystrophy (FSHD) typically presents with weakness of the facial muscles, the stabilizers of the scapula, or the dorsiflexors of the foot. Severity is highly variable. Weakness is slowly progressive and approximately 20% of affected individuals eventually require a wheelchair. Life expectancy is not shortened.
Myofibrillar myopathy 2
MedGen UID:
324735
Concept ID:
C1837317
Disease or Syndrome
Alpha-B crystallin-related myofibrillar myopathy is an autosomal dominant muscular disorder characterized by adult onset of progressive muscle weakness affecting both the proximal and distal muscles and associated with respiratory insufficiency, cardiomyopathy, and cataracts. There is phenotypic variability both within and between families (Fardeau et al., 1978; Selcen and Engel, 2003). A homozygous founder mutation in the CRYAB gene has been identified in Canadian aboriginal infants of Cree origin who have a severe fatal infantile hypertonic form of myofibrillar myopathy; see 613869. For a phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy, see MFM1 (601419).
Charcot-Marie-Tooth disease recessive intermediate A
MedGen UID:
334012
Concept ID:
C1842197
Disease or Syndrome
GDAP1-related hereditary motor and sensory neuropathy (GDAP1-HMSN) is a peripheral neuropathy (also known as a subtype of Charcot-Marie-Tooth disease) that typically affects the lower extremities earlier and more severely than the upper extremities. As the neuropathy progresses, the distal upper extremities also become severely affected. Proximal muscles can also become weak. Age at onset ranges from infancy to early childhood. In most cases, disease progression causes disabilities within the first or second decade of life. At the end of the second decade, most individuals are wheelchair bound. Disease progression varies considerably even within the same family. The neuropathy can be either of the demyelinating type with reduced nerve conduction velocities or the axonal type with normal nerve conduction velocities. Vocal cord paresis is common. Intelligence is normal. Life expectancy is usually normal, but on occasion may be reduced because of secondary complications.
Charcot-Marie-Tooth disease type 2J
MedGen UID:
375107
Concept ID:
C1843153
Disease or Syndrome
For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210).
Charcot-Marie-Tooth disease axonal type 2H
MedGen UID:
334344
Concept ID:
C1843173
Disease or Syndrome
An axonal peripheral sensorimotor polyneuropathy associated with pyramidal involvement. So far, it has been described in 13 members of a large Tunisian family. Onset occurred during the first decade of life with progressive distal atrophy involving both the upper and lower limbs, associated with a mild pyramidal syndrome (brisk patellar and upper limb reflexes, absent ankle reflexes and unattainable plantar reflexes). Transmitted in an autosomal recessive manner and the disease-causing locus has been mapped to 8q13-21.1.
Charcot-Marie-Tooth disease type 2E
MedGen UID:
375127
Concept ID:
C1843225
Disease or Syndrome
A form of axonal Charcot-Marie-Tooth disease a peripheral sensorimotor neuropathy. Onset is in the first to sixth decade with a gait anomaly and a leg weakness that reaches the arms secondarily. Tendon reflexes are reduced or absent and after years all patients have a pes cavus. Other signs may be present including hearing loss and postural tremor.
Charcot-Marie-Tooth disease type 1D
MedGen UID:
334709
Concept ID:
C1843247
Disease or Syndrome
For a phenotypic description and a discussion of genetic heterogeneity of autosomal dominant Charcot-Marie-Tooth disease type 1, see CMT1B (118200).
Charcot-Marie-Tooth disease X-linked recessive 3
MedGen UID:
375530
Concept ID:
C1844865
Disease or Syndrome
A rare genetic peripheral sensorimotor neuropathy with an X-linked recessive inheritance pattern and the childhood to adolescent-onset of progressive, distal muscle weakness and atrophy (beginning in the lower extremities and then affecting the upper extremities), as well as distal, pan sensory loss in the upper and lower extremities, pes cavus, and absent or reduced distal tendon reflexes. Pain and paraesthesia are frequently the initial sensory symptoms. Spastic paraparesis (manifested by clasp-knife sign, hyperactive deep-tendon reflexes, and Babinski sign) has also been reported.
Charcot-Marie-Tooth disease X-linked recessive 2
MedGen UID:
336803
Concept ID:
C1844873
Disease or Syndrome
A rare genetic peripheral sensorimotor neuropathy with an X-linked recessive inheritance pattern and the infantile to childhood-onset of progressive, distal muscle weakness and atrophy (more prominent in the lower extremities than in the upper extremities), pes cavus, and absent tendon reflexes. Sensory impairment and intellectual disability has been reported in some individuals.
Charcot-Marie-Tooth disease axonal type 2F
MedGen UID:
335784
Concept ID:
C1847823
Disease or Syndrome
A form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy with symmetric weakness primarily occurring in the lower limbs and reaching the arms only after 5 to 10 years, occasional and predominantly distal sensory loss and reduced tendon reflexes. Presents with gait anomaly between the first and sixth decade and early onset is generally associated to a more severe phenotype that may include foot drop.
Peroneus tertius muscle, absence of
MedGen UID:
376684
Concept ID:
C1850001
Congenital Abnormality
Nemaline myopathy 2
MedGen UID:
342534
Concept ID:
C1850569
Disease or Syndrome
Nemaline myopathy-2 (NEM2) is an autosomal recessive skeletal muscle disorder with a wide range of severity. The most common clinical presentation is early-onset (in infancy or childhood) muscle weakness predominantly affecting proximal limb muscles. Muscle biopsy shows accumulation of Z-disc and thin filament proteins into aggregates named 'nemaline bodies' or 'nemaline rods,' usually accompanied by disorganization of the muscle Z discs. The clinical and histologic spectrum of entities caused by variants in the NEB gene is a continuum, ranging in severity. The distribution of weakness can vary from generalized muscle weakness, more pronounced in proximal limb muscles, to distal-only involvement, although neck flexor weakness appears to be rather consistent. Histologic patterns range from a severe usually nondystrophic disturbance of the myofibrillar pattern to an almost normal pattern, with or without nemaline bodies, sometimes combined with cores (summary by Lehtokari et al., 2014). Genetic Heterogeneity of Nemaline Myopathy See also NEM1 (255310), caused by mutation in the tropomyosin-3 gene (TPM3; 191030) on chromosome 1q22; NEM3 (161800), caused by mutation in the alpha-actin-1 gene (ACTA1; 102610) on chromosome 1q42; NEM4 (609285), caused by mutation in the beta-tropomyosin gene (TPM2; 190990) on chromosome 9p13; NEM5A (605355), also known as Amish nemaline myopathy, NEM5B (620386), and NEM5C (620389), all caused by mutation in the troponin T1 gene (TNNT1; 191041) on chromosome 19q13; NEM6 (609273), caused by mutation in the KBTBD13 gene (613727) on chromosome 15q22; NEM7 (610687), caused by mutation in the cofilin-2 gene (CFL2; 601443) on chromosome 14q13; NEM8 (615348), caused by mutation in the KLHL40 gene (615340), on chromosome 3p22; NEM9 (615731), caused by mutation in the KLHL41 gene (607701) on chromosome 2q31; NEM10 (616165), caused by mutation in the LMOD3 gene (616112) on chromosome 3p14; and NEM11 (617336), caused by mutation in the MYPN gene (608517) on chromosome 10q21. Several of the genes encode components of skeletal muscle sarcomeric thin filaments (Sanoudou and Beggs, 2001). Mutations in the NEB gene are the most common cause of nemaline myopathy (Lehtokari et al., 2006).
Charcot-Marie-Tooth disease axonal type 2C
MedGen UID:
342947
Concept ID:
C1853710
Disease or Syndrome
The autosomal dominant TRPV4 disorders (previously considered to be clinically distinct phenotypes before their molecular basis was discovered) are now grouped into neuromuscular disorders and skeletal dysplasias; however, the overlap within each group is considerable. Affected individuals typically have either neuromuscular or skeletal manifestations alone, and in only rare instances an overlap syndrome has been reported. The three autosomal dominant neuromuscular disorders (mildest to most severe) are: Charcot-Marie-Tooth disease type 2C. Scapuloperoneal spinal muscular atrophy. Congenital distal spinal muscular atrophy. The autosomal dominant neuromuscular disorders are characterized by a congenital-onset, static, or later-onset progressive peripheral neuropathy with variable combinations of laryngeal dysfunction (i.e., vocal fold paresis), respiratory dysfunction, and joint contractures. The six autosomal dominant skeletal dysplasias (mildest to most severe) are: Familial digital arthropathy-brachydactyly. Autosomal dominant brachyolmia. Spondylometaphyseal dysplasia, Kozlowski type. Spondyloepiphyseal dysplasia, Maroteaux type. Parastremmatic dysplasia. Metatropic dysplasia. The skeletal dysplasia is characterized by brachydactyly (in all 6); the five that are more severe have short stature that varies from mild to severe with progressive spinal deformity and involvement of the long bones and pelvis. In the mildest of the autosomal dominant TRPV4 disorders life span is normal; in the most severe it is shortened. Bilateral progressive sensorineural hearing loss (SNHL) can occur with both autosomal dominant neuromuscular disorders and skeletal dysplasias.
Autosomal recessive distal spinal muscular atrophy 2
MedGen UID:
344189
Concept ID:
C1854023
Disease or Syndrome
Autosomal recessive distal hereditary motor neuronopathy-2 (HMNR2) is a neuromuscular disorder characterized by onset of distal muscle weakness and wasting affecting the lower and upper limbs in the first decade; there is no sensory involvement (summary by Li et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive HMN, see HMNR1 (604320).
Charcot-Marie-Tooth disease type 2B1
MedGen UID:
343064
Concept ID:
C1854154
Disease or Syndrome
Charcot-Marie-Tooth disease constitutes a clinically and genetically heterogeneous group of hereditary motor and sensory neuropathies. On the basis of electrophysiologic criteria, CMT is divided into 2 major types: type 1, the demyelinating form, characterized by a motor median nerve conduction velocity less than 38 m/s (see CMT1B; 118200); and type 2, the axonal form, with a normal or slightly reduced nerve conduction velocity. For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT type 2, see CMT2A1 (118210).
Charcot-Marie-Tooth disease type 4B2
MedGen UID:
346869
Concept ID:
C1858278
Disease or Syndrome
Autosomal recessive Charcot-Marie-Tooth disease type 4B is a demyelinating hereditary motor and sensory neuropathy characterized by abnormal folding of myelin sheaths. CMT4B1 (601382) is a clinically similar disorder caused by mutation in the MTMR2 gene (603557) on 11q22. For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive demyelinating CMT, see CMT4A (214400).
Charcot-Marie-Tooth disease type 2A1
MedGen UID:
350076
Concept ID:
C1861678
Disease or Syndrome
MFN2 hereditary motor and sensory neuropathy (MFN2-HMSN) is a classic axonal peripheral sensorimotor neuropathy, inherited in either an autosomal dominant (AD) manner (~90%) or an autosomal recessive (AR) manner (~10%). MFN2-HMSN is characterized by more severe involvement of the lower extremities than the upper extremities, distal upper-extremity involvement as the neuropathy progresses, more prominent motor deficits than sensory deficits, and normal (>42 m/s) or only slightly decreased nerve conduction velocities (NCVs). Postural tremor is common. Median onset is age 12 years in the AD form and age eight years in the AR form. The prevalence of optic atrophy is approximately 7% in the AD form and approximately 20% in the AR form.
Myopathy, myofibrillar, 9, with early respiratory failure
MedGen UID:
350930
Concept ID:
C1863599
Disease or Syndrome
Hereditary myopathy with early respiratory failure (HMERF) is a slowly progressive myopathy that typically begins in the third to fifth decades of life. The usual presenting findings are gait disturbance relating to distal leg weakness or nocturnal respiratory symptoms due to respiratory muscle weakness. Weakness eventually generalizes and affects both proximal and distal muscles. Most affected individuals require walking aids within a few years of onset; some progress to wheelchair dependence and require nocturnal noninvasive ventilatory support about ten years after onset. The phenotype varies even among individuals within the same family: some remain ambulant until their 70s whereas others may require ventilator support in their 40s.
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.
Vacuolar Neuromyopathy
MedGen UID:
355637
Concept ID:
C1866139
Disease or Syndrome
Autosomal dominant myopathy with rimmed ubiquitin-positive autophagic vacuolation (MRUPAV) is characterized by adult onset of slowly progressive skeletal muscle weakness variably affecting the distal or proximal lower limbs. Some patients may also have upper limb involvement or neck muscle weakness, but respiratory and bulbar involvement only rarely occurs. EMG studies show a myopathic process, and myotonia may also be observed. Skeletal muscle biopsy shows myopathic features, rimmed vacuoles, and abnormal subsarcolemmal protein aggregation with activation of the autophagy pathway (Ruggieri et al., 2020).
Neurogenic scapuloperoneal syndrome, Kaeser type
MedGen UID:
356670
Concept ID:
C1867005
Disease or Syndrome
A rare genetic neuromuscular disease with characteristics of adult-onset muscle weakness and atrophy in a scapuloperoneal distribution, mild involvement of the facial muscles, dysphagia, and gynaecomastia. Elevated serum CK levels and mixed myopathic and neurogenic abnormalities are associated clinical findings. Caused by heterozygous mutation in the DES gene on chromosome 2q35.
X-linked scapuloperoneal muscular dystrophy
MedGen UID:
395530
Concept ID:
C2678061
Disease or Syndrome
A rare, genetic, muscular dystrophy disease characterized by the co-occurrence of late onset scapular and peroneal muscle weakness, principally manifesting with distal lower limb and proximal upper limb weakness and scapular winging.
Charcot-Marie-Tooth disease axonal type 2N
MedGen UID:
413754
Concept ID:
C2750090
Disease or Syndrome
A mild form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy, with characteristics of distal legs sensory loss and weakness that can be asymmetric. Tendon reflexes are reduced in the knees and absent in ankles. Progression is slow.
Charcot-Marie-Tooth disease recessive intermediate B
MedGen UID:
462247
Concept ID:
C3150897
Disease or Syndrome
An extremely rare subtype of autosomal recessive intermediate Charcot-Marie-Tooth (CMT) disease characterized by a CMT neuropathy associated with developmental delay, self-abusive behavior, dysmorphic features and vestibular Schwannoma. Motor nerve conduction velocities demonstrate features of both demyelinating and axonal pathology.
Neuropathy, hereditary sensory, type 2C
MedGen UID:
481798
Concept ID:
C3280168
Disease or Syndrome
Hereditary sensory and autonomic neuropathy type II (HSAN2) is characterized by progressively reduced sensation to pain, temperature, and touch. Onset can be at birth and is often before puberty. The sensory deficit is predominantly distal with the lower limbs more severely affected than the upper limbs. Over time sensory function becomes severely reduced. Unnoticed injuries and neuropathic skin promote ulcerations and infections that result in spontaneous amputation of digits or the need for surgical amputation. Osteomyelitis is common. Painless fractures can complicate the disease. Autonomic disturbances are variable and can include hyperhidrosis, tonic pupils, and urinary incontinence in those with more advanced disease.
Charcot-Marie-Tooth disease axonal type 2P
MedGen UID:
482427
Concept ID:
C3280797
Disease or Syndrome
A rare genetic axonal hereditary motor and sensory neuropathy disorder with characteristics of adulthood-onset of slowly progressive, occasionally asymmetrical, distal muscle weakness and atrophy (predominantly in the lower limbs), pan-modal sensory loss, muscle cramping in extremities and/or trunk, pes cavus and absent or reduced deep tendon reflexes. Gait anomalies and variable autonomic disturbances, such as erectile dysfunction and urinary urgency, may be associated. The disease can be caused by homozygous or heterozygous mutation in the LRSAM1 gene on chromosome 9q33.
Charcot-Marie-Tooth disease type 1E
MedGen UID:
501212
Concept ID:
C3495591
Disease or Syndrome
A rare subtype of CMT1 characterized by a variable clinical presentation. Onset within the first two years of life with a delay in walking is not uncommon; however, onset may occur later. CMT1E is caused by point mutations in the <i>PMP22</i> (17p12) gene. The disease severity depends on the particular <i>PMP22</i> mutation, with some cases being very mild and even resembling hereditary neuropathy with liability to pressure palsies, while others having an earlier onset with a more severe phenotype (reminiscent of Dejerine-Sottas syndrome) than that seen in CMT1A, caused by gene duplication. These severe cases may also report deafness and much slower motor nerve conduction velocities compared to CMT1A patients.
Hereditary spastic paraplegia 55
MedGen UID:
761342
Concept ID:
C3539506
Disease or Syndrome
A rare complex type of hereditary spastic paraplegia with characteristics of childhood onset of progressive spastic paraplegia associated with optic atrophy (with reduced visual acuity and central scotoma), ophthalmoplegia, reduced upper-extremity strength and dexterity, muscular atrophy in the lower extremities and sensorimotor neuropathy. Caused by mutations in the C12ORF65 gene (12q24.31) encoding probable peptide chain release factor C12ORF65, mitochondrial.
Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3
MedGen UID:
815799
Concept ID:
C3809469
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.
Myopathy, distal, infantile-onset
MedGen UID:
860162
Concept ID:
C4011725
Disease or Syndrome
Myopathy, tubular aggregate, 2
MedGen UID:
862994
Concept ID:
C4014557
Disease or Syndrome
Any tubular aggregate myopathy in which the cause of the disease is a mutation in the ORAI1 gene.
Congenital myasthenic syndrome 7
MedGen UID:
863475
Concept ID:
C4015038
Disease or Syndrome
Presynaptic congenital myasthenic syndrome-7A with distal motor neuropathy (CMS7A) is an autosomal dominant neuromuscular disorder characterized by onset of foot deformities, delayed motor development, and slowly progressive distal muscle weakness resulting in gait difficulties in early childhood. Other features may include hyporeflexia, muscle atrophy, and upper limb involvement. Electrophysiologic studies show low compound muscle action potentials (CMAPs), consistent with a distal hereditary motor neuropathy (dHMN), as well as a decremental response to repetitive stimulation, indicating presynaptic defects at the neuromuscular junction (NMJ), consistent with myasthenic syndrome (summary by Fionda et al., 2021). The complex phenotype of patients with dominant SYT2 mutations likely results from impairment of 2 fundamental functions of SYT2: (1) disturbance of calcium-dependent synchronous presynaptic neurotransmitter release, resulting in a myasthenic disorder, and (2) disruption of exocytosis and endocytosis, causing a degenerative process affecting peripheral motor nerve terminals and resulting in a motor neuropathy (Maselli et al., 2021). For a discussion of genetic heterogeneity of CMS, see CMS1A (601462). For a discussion of genetic heterogeneity of dHMN, see 182960.
Charcot-Marie-Tooth disease axonal type 2S
MedGen UID:
863786
Concept ID:
C4015349
Disease or Syndrome
Charcot-Marie-Tooth disease type 2S is a relatively pure form of autosomal recessive axonal neuropathy characterized by onset in the first decade of slowly progressive distal muscle weakness and atrophy affecting the lower and upper limbs. Patients have decreased reflexes and variable distal sensory impairment (summary by Cottenie et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210).
Charcot-Marie-Tooth disease axonal type 2T
MedGen UID:
864072
Concept ID:
C4015635
Disease or Syndrome
Charcot-Marie-Tooth disease type 2T (CMT2T) is a slowly progressive autosomal recessive sensorimotor peripheral neuropathy with onset in middle age (Higuchi et al., 2016). For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210).
Charcot-Marie-Tooth disease axonal type 2U
MedGen UID:
906504
Concept ID:
C4084821
Disease or Syndrome
Charcot-Marie-Tooth disease type 2U (CMT2U) is an autosomal dominant neurologic disorder characterized by late-adult onset of distal sensory impairment resulting in distal muscle weakness and atrophy affecting the upper and lower limbs. The disorder is slowly progressive (summary by Gonzalez et al., 2013). For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210).
Progressive scapulohumeroperoneal distal myopathy
MedGen UID:
905125
Concept ID:
C4225181
Disease or Syndrome
Scapulohumeroperoneal myopathy is an autosomal dominant muscle disorder characterized by slowly progressive muscle weakness and atrophy affecting both proximal and distal muscles of the upper and lower limbs. Onset is usually in the first decade and can be as early as infancy, although some patients do not notice symptoms until young adulthood. There is marked variability in severity (summary by Zukosky et al., 2015).
Charcot-Marie-Tooth disease dominant intermediate E
MedGen UID:
928336
Concept ID:
C4302667
Disease or Syndrome
Autosomal dominant intermediate Charcot-Marie-Tooth disease E with focal segmental glomerulonephritis is characterized by the neurologic features of CMT, including distal muscle weakness and atrophy and distal sensory loss, and the features of FSGS, including proteinuria, progression to end-stage renal disease, and a characteristic histologic pattern on renal biopsy (summary by Boyer et al., 2011). Isolated focal segmental glomerulosclerosis-5 (FSGS5; 613237) is also caused by heterozygous mutation in the INF2 gene. For a discussion of genetic heterogeneity of CMTDI, see 606482.
Encephalopathy, progressive, with amyotrophy and optic atrophy
MedGen UID:
934634
Concept ID:
C4310667
Disease or Syndrome
Progressive encephalopathy with amyotrophy and optic atrophy (PEAMO) is a severe autosomal recessive neurodegenerative disorder characterized by delayed development with hypotonia apparent in infancy and subsequent motor regression. Most affected individuals are unable to or lose the ability to sit and show distal amyotrophy and weakness of all 4 limbs. The patients are cognitively impaired and unable to speak or have severe dysarthria. Additional features include optic atrophy, thin corpus callosum, and cerebellar atrophy (Sferra et al., 2016).
Myofibrillar myopathy 7
MedGen UID:
934678
Concept ID:
C4310711
Disease or Syndrome
Myofibrillar myopathy-7 (MFM7) is an autosomal recessive muscle disorder characterized by early childhood onset of slowly progressive muscle weakness that primarily affects the lower limbs and is associated with joint contractures (summary by Straussberg et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy, see MFM1 (601419).
Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b;
MedGen UID:
934692
Concept ID:
C4310725
Disease or Syndrome
MFN2 hereditary motor and sensory neuropathy (MFN2-HMSN) is a classic axonal peripheral sensorimotor neuropathy, inherited in either an autosomal dominant (AD) manner (~90%) or an autosomal recessive (AR) manner (~10%). MFN2-HMSN is characterized by more severe involvement of the lower extremities than the upper extremities, distal upper-extremity involvement as the neuropathy progresses, more prominent motor deficits than sensory deficits, and normal (>42 m/s) or only slightly decreased nerve conduction velocities (NCVs). Postural tremor is common. Median onset is age 12 years in the AD form and age eight years in the AR form. The prevalence of optic atrophy is approximately 7% in the AD form and approximately 20% in the AR form.
Charcot-Marie-Tooth disease type 2A2
MedGen UID:
1648317
Concept ID:
C4721887
Disease or Syndrome
MFN2 hereditary motor and sensory neuropathy (MFN2-HMSN) is a classic axonal peripheral sensorimotor neuropathy, inherited in either an autosomal dominant (AD) manner (~90%) or an autosomal recessive (AR) manner (~10%). MFN2-HMSN is characterized by more severe involvement of the lower extremities than the upper extremities, distal upper-extremity involvement as the neuropathy progresses, more prominent motor deficits than sensory deficits, and normal (>42 m/s) or only slightly decreased nerve conduction velocities (NCVs). Postural tremor is common. Median onset is age 12 years in the AD form and age eight years in the AR form. The prevalence of optic atrophy is approximately 7% in the AD form and approximately 20% in the AR form.
Charcot-Marie-Tooth disease type 5
MedGen UID:
1648461
Concept ID:
C4721916
Disease or Syndrome
Hereditary motor and sensory neuropathies (HMSN) are a heterogeneous group of peripheral nervous system disorders affecting motor and sensory function. HMSN I, also known as Charcot-Marie-Tooth (CMT) disease, or peroneal muscular atrophy, type 1, is a demyelinating neuropathy (see CMT1B; 118200) and HMSN II, also known as CMT type 2, is an axonal neuropathy (see CMT2A1; 118210). See also HMSN III (145900) and HMSN IV (266500). For an autosomal recessive disorder with similarities to HMSN V, see 607731.
Charcot-marie-tooth disease, axonal, type 2DD
MedGen UID:
1648475
Concept ID:
C4747974
Disease or Syndrome
Charcot-Marie-Tooth disease type 2DD is an autosomal dominant peripheral sensorimotor neuropathy mainly affecting the lower limbs. Affected individuals have gait impairment due to distal muscle weakness and atrophy. Some patients may also have involvement of the distal upper limbs, resulting in atrophy of the intrinsic hand muscles. The age at onset and severity of the disorder is highly variable, even within families, and those with earlier onset in late childhood or the teenage years tend to have a more severe disease course. Patients remain ambulatory even late in the disease, although some may require orthotic devices (summary by Lassuthova et al., 2018). For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT type 2, see CMT2A (118210).
Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development
MedGen UID:
1648480
Concept ID:
C4748283
Disease or Syndrome
Autosomal recessive peripheral neuropathy with or without impaired intellectual development is an early childhood-onset neurologic disorder characterized by slowly progressive distal motor impairment resulting in gait difficulties, often with loss of ambulation, and difficulties using the hands in most patients. Most affected individuals also have impaired intellectual development, although some have normal cognition. Electrophysiologic testing and sural nerve biopsy are most compatible with an axonal motor neuropathy; some patients may show signs of demyelination. Additional features may include eye movement abnormalities, claw hands, foot deformities, and scoliosis (summary by Ylikallio et al., 2017).
Young adult-onset distal hereditary motor neuropathy
MedGen UID:
1667915
Concept ID:
C4749918
Disease or Syndrome
HMNR5 is an autosomal recessive neurologic disorder characterized by young adult onset of slowly progressive distal muscle weakness and atrophy resulting in gait impairment and loss of reflexes due to impaired function of motor nerves. Sensation and cognition are not impaired (summary by Blumen et al., 2012). For a discussion of genetic heterogeneity of autosomal recessive HMN, see HMNR1 (604320).
Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 3
MedGen UID:
1673607
Concept ID:
C5193070
Disease or Syndrome
Spinocerebellar ataxia with axonal neuropathy-3 (SCAN3) is an autosomal recessive neuromuscular disorder characterized by onset in the first decade of slowly progressive distal muscle weakness and atrophy and distal sensory impairment due to an axonal peripheral neuropathy. Affected individuals have gait disturbances and sometimes manual dexterity difficulties, as well as cerebellar ataxia associated with cerebellar atrophy on brain imaging. Additional features usually include dysarthria, hyporeflexia, and increased serum creatine kinase. Some patients may have impaired intellectual development (summary by Higuchi et al., 2018). For a discussion of genetic heterogeneity of SCAN, see SCAN1 (607250).
Charcot-Marie-Tooth disease, axonal, type 2EE
MedGen UID:
1677426
Concept ID:
C5193076
Disease or Syndrome
Charcot-Marie-Tooth disease type 2EE (CMT2EE) is an autosomal recessive sensorimotor peripheral axonal neuropathy with onset in the first or second decades of life. The disorder primarily affects the lower limbs and is slowly progressive, sometimes resulting in loss of ambulation, with later onset of upper limb involvement. There is significant distal muscle weakness and atrophy, usually with foot or hand deformities. Skeletal muscle biopsy shows findings of disturbed mitochondrial maintenance. Cognition is unaffected, and chronic liver disease is absent (summary by Baumann et al., 2019). For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT type 2, see CMT2A (118210).
Myopathy, distal, 6, adult-onset, autosomal dominant
MedGen UID:
1684760
Concept ID:
C5203349
Disease or Syndrome
Autosomal dominant adult-onset distal myopathy-6 (MPD6) is a muscle disorder characterized by slowly progressive distal muscle weakness, primarily affecting the lower limbs and resulting in gait difficulties. Some patients develop involvement of proximal and upper limb muscles (summary by Savarese et al., 2019)
Oculopharyngodistal myopathy 1
MedGen UID:
1684682
Concept ID:
C5231388
Disease or Syndrome
Oculopharyngodistal myopathy-1 (OPDM1) is an autosomal dominant disorder characterized by adult-onset ptosis, external ophthalmoplegia, facial muscle weakness, distal limb muscle weakness and atrophy, and pharyngeal involvement, resulting in dysphagia and dysarthria. Skeletal muscle biopsy shows myopathic changes with rimmed vacuoles. There are variable manifestations of the disorder regarding muscle involvement and severity (summary by Ishiura et al., 2019). Genetic Heterogeneity of Oculopharyngodistal Myopathy See also OPDM2 (618940), caused by trinucleotide repeat expansion in the GIPC1 gene (605072) on chromosome 19p13; OPDM3 (619473), caused by trinucleotide repeat expansion in the NOTCH2NLC gene (618025) on chromosome 1q21; and OPDM4 (619790), caused by trinucleotide repeat expansion in the RILPL1 gene (614092) on chromosome 12q24. Oculopharyngeal muscular dystrophy (OPMD; 164300) is a similar disorder with overlapping features. It is caused by a similar heterozygous trinucleotide repeat expansion in the PABPN1 gene (602279) (summary by Durmus et al., 2011).
Mitochondrial DNA depletion syndrome 18
MedGen UID:
1713890
Concept ID:
C5394140
Disease or Syndrome
Mitochondrial DNA depletion syndrome-18 (MTDPS18) is an autosomal recessive neuromuscular disorder characterized by early-onset progressive weakness and atrophy of the distal limb muscles, resulting in loss of ambulation as well as atrophy of the intrinsic hand muscles with clawed hands. Affected individuals may also develop scoliosis and have hypo- or hyperreflexia and decreased pulmonary vital capacity. Examination of skeletal muscle shows neurogenic atrophy and combined mitochondrial oxidative phosphorylation deficiency associated with mtDNA depletion. The clinical phenotype is reminiscent of spinal muscular atrophy (see SMA, 253300) and the metabolic profile is reminiscent of 2-aminoadipic 2-oxoadipic aciduria (AMOXAD; 204750), which is caused by mutation in the DHTKD1 gene (614984) (summary by Boczonadi et al., 2018). For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041).
Myopathy, distal, with rimmed vacuoles
MedGen UID:
1728314
Concept ID:
C5399975
Disease or Syndrome
Distal myopathy with rimmed vacuoles (DMRV) is an autosomal dominant myopathic disorder characterized by adult onset of muscle weakness affecting the distal upper and lower limbs, which may result in walking difficulties, as well as proximal weakness of the shoulder girdle muscles. Muscle biopsy shows rimmed vacuoles (summary by Bucelli et al., 2015).
Mitochondrial complex 4 deficiency, nuclear type 11
MedGen UID:
1760275
Concept ID:
C5436694
Disease or Syndrome
Mitochondrial complex IV deficiency nuclear type 11 (MC4DN11) is an autosomal recessive metabolic disorder characterized by a childhood-onset sensory neuronopathy and additional features which may include hypotonia, cerebellar ataxia, tremor, dystonia, choreoathetosis, and/or dysarthria. Patients may have variable motor delay, speech delay, or impaired intellectual development (summary by Doss et al., 2014; Otero et al., 2019; Xu et al., 2019; Dong et al., 2021). For a discussion of genetic heterogeneity of mitochondrial complex IV (cytochrome c oxidase) deficiency, see 220110.
Neuropathy, hereditary motor, with myopathic features
MedGen UID:
1786836
Concept ID:
C5543119
Disease or Syndrome
Autosomal recessive distal hereditary motor neuronopathy-7 (HMNR7) is characterized by onset of lower leg weakness in the first decade. Affected individuals have difficulty climbing stairs and problems standing on the heels. Some patients have later onset well into the adult years. Most patients have foot deformities, and some may have leg muscle atrophy. The disorder is slowly progressive and often involves the upper limbs. Muscle biopsy and electrophysiologic studies are consistent with both a myopathic process and an axonal motor neuropathy. Sensory abnormalities are not typically present, and patients remain ambulatory. The phenotype shows phenotypic overlap with distal hereditary motor neuropathy, but can distinguished by the presence of myopathic features (summary by Deschauer et al., 2021 and Pagnamenta et al., 2021). For a discussion of genetic heterogeneity of autosomal recessive HMN, see HMNR1 (604320).
Charcot-Marie-Tooth Disease, axonal, type 2GG
MedGen UID:
1794143
Concept ID:
C5561933
Disease or Syndrome
Charcot-Marie-Tooth disease type 2GG (CMT2GG) is an autosomal dominant axonal peripheral neuropathy characterized by slowly progressive distal muscle weakness and atrophy primarily affecting the lower limbs and causing difficulty walking. The onset is usually in adulthood, although rare patients may have mild symptoms from childhood. Some individuals may also have involvement of the hands. Although most patients have hypo- or areflexia at the ankles, distal sensory impairment is not always present, indicating a spectrum of disease encompassing both distal hereditary neuropathy and axonal CMT. Electrophysiologic studies are consistent with a axonal process (summary by Mendoza-Ferreira et al., 2020). For a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210).
Neurodevelopmental disorder with hypotonia and dysmorphic facies
MedGen UID:
1794184
Concept ID:
C5561974
Disease or Syndrome
Neurodevelopmental disorder with hypotonia and dysmorphic facies (NEDHYDF) is characterized by global developmental delay and hypotonia apparent from birth. Affected individuals have variably impaired intellectual development, often with speech delay and delayed walking. Seizures are generally not observed, although some patients may have single seizures or late-onset epilepsy. Most patients have prominent dysmorphic facial features. Additional features may include congenital cardiac defects (without arrhythmia), nonspecific renal anomalies, joint contractures or joint hyperextensibility, dry skin, and cryptorchidism. There is significant phenotypic variability in both the neurologic and extraneurologic manifestations (summary by Tan et al., 2022).
Charcot-Marie-Tooth disease, axonal, type 2FF
MedGen UID:
1794191
Concept ID:
C5561981
Disease or Syndrome
Charcot-Marie-Tooth disease type 2FF (CMT2FF) is an autosomal dominant progressive axonal sensorimotor peripheral neuropathy characterized by early-childhood onset of difficulties walking or running due to atrophy and weakness of the lower limbs. Most patients have foot and ankle deformities, requiring surgery or walking aids. Some patients lose independent ambulation. There is also prominent involvement of the upper limbs, with weakness and atrophy of the forearm, wrist, and intrinsic hand muscles. Proximal muscle function is preserved. Affected individuals have variable distal sensory impairment. Most patients have hyporeflexia, although brisk reflexes, suggesting upper motor involvement, have been described in 1 family. Sural nerve biopsy showed abnormal myelination (Rebelo et al., 2021). For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT type 2, see CMT2A (118210).
Charcot-Marie-Tooth disease, axonal, Type 2HH
MedGen UID:
1794213
Concept ID:
C5562003
Disease or Syndrome
Axonal Charcot-Marie-Tooth disease type 2HH (CMT2HH) is an autosomal dominant peripheral neuropathy characterized predominantly by onset of vocal cord weakness resulting in stridor in infancy or early childhood. The vocal cord paresis remains throughout life and may be severe enough to require tracheostomy. Additional features of the disorder usually include pes cavus and scoliosis. Some patients have mild distal muscle weakness and atrophy primarily affecting the lower limbs, although the upper limbs may also be involved, and distal sensory impairment, often with hyporeflexia (Sullivan et al., 2020). For a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210).
Autosomal recessive complex spastic paraplegia type 9B
MedGen UID:
1800403
Concept ID:
C5568980
Disease or Syndrome
Autosomal recessive SPG9B is a neurologic disorder characterized by early-onset complex spastic paraplegia. Affected individuals had delayed psychomotor development, intellectual disability, and severe motor impairment. More variable features include dysmorphic facial features, tremor, and urinary incontinence (summary by Coutelier et al., 2015). For a discussion of genetic heterogeneity of autosomal recessive SPG, see SPG5A (270800).
Charcot-Marie-Tooth disease axonal type 2X
MedGen UID:
1800447
Concept ID:
C5569024
Disease or Syndrome
Charcot-Marie-Tooth disease type 2X (CMT2X) is an autosomal recessive, slowly progressive, axonal peripheral sensorimotor neuropathy characterized by lower limb muscle weakness and atrophy associated with distal sensory impairment and gait difficulties. Some patients also have involvement of the upper limbs. Onset usually occurs in the first 2 decades of life, although later onset can also occur (summary by Montecchiani et al., 2016) For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210).
Charcot-Marie-Tooth disease axonal type 2Z
MedGen UID:
1800448
Concept ID:
C5569025
Disease or Syndrome
Charcot-Marie-Tooth disease type 2Z (CMT2Z) is an autosomal dominant axonal peripheral neuropathy characterized by onset, usually in the first decade, of distal lower limb muscle weakness and sensory impairment. The disorder is progressive, and affected individuals tend to develop upper limb and proximal muscle involvement in an asymmetric pattern, resulting in severe disability late in adulthood. Rare occurrence of global developmental delay with impaired intellectual development or learning difficulties has been observed. In some instances, the same mutation may result in different phenotypic manifestations (CMT2Z or DIGFAN), which highlights the clinical spectrum associated with MORC2 mutations and may render the classification of patients into one or the other disorder challenging (summary by Sevilla et al., 2016, Ando et al., 2017, Guillen Sacoto et al., 2020). For a phenotypic description and a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210).
Charcot-Marie-Tooth disease recessive intermediate D
MedGen UID:
1800450
Concept ID:
C5569027
Disease or Syndrome
A rare hereditary motor and sensory neuropathy with characteristics of childhood onset of unsteady gait, pes cavus, frequent falls and foot dorsiflexor weakness slowly progressing to distal upper and lower limb muscle weakness and atrophy, distal sensory impairment and reduced tendon reflexes. Additional symptoms may include bilateral sensorineural hearing impairment and neuropathic pain.
Autosomal recessive axonal neuropathy with neuromyotonia
MedGen UID:
1814513
Concept ID:
C5700127
Disease or Syndrome
NMAN is an autosomal recessive neurologic disorder characterized by onset in the first or second decade of a peripheral axonal neuropathy predominantly affecting motor more than sensory nerves. The axonal neuropathy is reminiscent of Charcot-Marie-Tooth disease type 2 (see, e.g., CMT2A1, 118210) and distal hereditary motor neuropathy (see, e.g., HMND1, 182960). Individuals with NMAN also have delayed muscle relaxation and action myotonia associated with neuromyotonic discharges on needle EMG resulting from hyperexcitability of the peripheral nerves (summary by Zimon et al., 2012).
Spinal muscular atrophy, distal, autosomal recessive, 6
MedGen UID:
1823974
Concept ID:
C5774201
Disease or Syndrome
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).
Charcot-Marie-Tooth disease, axonal, IIa 2II
MedGen UID:
1824000
Concept ID:
C5774227
Disease or Syndrome
Axonal Charcot-Marie-Tooth disease type 2II (CMT2II) is an autosomal dominant neurologic disorder characterized by a slowly progressive sensorimotor peripheral neuropathy affecting mainly the lower limbs, resulting in distal muscle weakness and atrophy and subsequent walking difficulties. Some patients may have upper limb involvement with atrophy of the intrinsic hand muscles. The age at onset is highly variable, ranging from infancy to adulthood. Electrophysiologic studies are usually consistent with an axonal process, although some may show intermediate or even demyelinating values (Park et al., 2020; Ando et al., 2022). One family with possible autosomal recessive inheritance has been reported (Bogdanova-Mihaylova et al., 2021). For a discussion of genetic heterogeneity of axonal CMT, see CMT2A1 (118210).
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

Deltombe T, Wautier D, De Cloedt P, Fostier M, Gustin T
J Rehabil Med 2017 Jun 28;49(6):461-468. doi: 10.2340/16501977-2226. PMID: 28451697
Jaivin JS, Bishop JO, Braly WG, Tullos HS
Foot Ankle 1992 Feb;13(2):98-104. doi: 10.1177/107110079201300209. PMID: 1349293

Recent clinical studies

Etiology

Khadilkar SV, Chaudhari AD, Singla MB, Dastur RS, Gaitonde PS, Bhutada AG, Hegde MR
Muscle Nerve 2021 Feb;63(2):199-203. Epub 2020 Nov 28 doi: 10.1002/mus.27117. PMID: 33197058
Arnold JB, Halstead J, Grainger AJ, Keenan AM, Hill CL, Redmond AC
Arthritis Care Res (Hoboken) 2021 Jun;73(6):772-780. doi: 10.1002/acr.24182. PMID: 32170831
Sackley C, Disler PB, Turner-Stokes L, Wade DT, Brittle N, Hoppitt T
Cochrane Database Syst Rev 2009 Jul 8;(3):CD003908. doi: 10.1002/14651858.CD003908.pub3. PMID: 19588347
Sackley C, Disler PB, Turner-Stokes L, Wade DT
Cochrane Database Syst Rev 2007 Apr 18;(2):CD003908. doi: 10.1002/14651858.CD003908.pub2. PMID: 17443532
Gefen A
IEEE Trans Neural Syst Rehabil Eng 2001 Dec;9(4):333-7. doi: 10.1109/7333.1000112. PMID: 12018645

Diagnosis

Conde RM, Senem I, Dos Santos M, de Lima Osório F, Marques Júnior W
J Peripher Nerv Syst 2023 Jun;28(2):169-178. Epub 2023 Apr 24 doi: 10.1111/jns.12548. PMID: 37060329
Arnold JB, Halstead J, Grainger AJ, Keenan AM, Hill CL, Redmond AC
Arthritis Care Res (Hoboken) 2021 Jun;73(6):772-780. doi: 10.1002/acr.24182. PMID: 32170831
Barnes A, Sullivan J, Pappas E, Adams R, Burns J
PM R 2017 Nov;9(11):1128-1134. Epub 2017 Apr 28 doi: 10.1016/j.pmrj.2017.04.009. PMID: 28461226
Deltombe T, Wautier D, De Cloedt P, Fostier M, Gustin T
J Rehabil Med 2017 Jun 28;49(6):461-468. doi: 10.2340/16501977-2226. PMID: 28451697
Broström E, Nordlund MM, Cresswell AG
Arch Phys Med Rehabil 2004 Aug;85(8):1224-30. doi: 10.1016/j.apmr.2003.11.017. PMID: 15295744

Therapy

Kim N
Hum Vaccin Immunother 2023 Dec 15;19(3):2265657. Epub 2023 Oct 11 doi: 10.1080/21645515.2023.2265657. PMID: 37818712Free PMC Article
Conde RM, Senem I, Dos Santos M, de Lima Osório F, Marques Júnior W
J Peripher Nerv Syst 2023 Jun;28(2):169-178. Epub 2023 Apr 24 doi: 10.1111/jns.12548. PMID: 37060329
Sackley C, Disler PB, Turner-Stokes L, Wade DT, Brittle N, Hoppitt T
Cochrane Database Syst Rev 2009 Jul 8;(3):CD003908. doi: 10.1002/14651858.CD003908.pub3. PMID: 19588347
Sackley C, Disler PB, Turner-Stokes L, Wade DT
Cochrane Database Syst Rev 2007 Apr 18;(2):CD003908. doi: 10.1002/14651858.CD003908.pub2. PMID: 17443532
Ericson U, Borg J, Borg K
Muscle Nerve 2000 Feb;23(2):217-22. doi: 10.1002/(sici)1097-4598(200002)23:2<217::aid-mus12>3.0.co;2-a. PMID: 10639614

Prognosis

Khadilkar SV, Chaudhari AD, Singla MB, Dastur RS, Gaitonde PS, Bhutada AG, Hegde MR
Muscle Nerve 2021 Feb;63(2):199-203. Epub 2020 Nov 28 doi: 10.1002/mus.27117. PMID: 33197058
Banerji CRS, Cammish P, Evangelista T, Zammit PS, Straub V, Marini-Bettolo C
Neuromuscul Disord 2020 Apr;30(4):315-328. Epub 2020 Mar 12 doi: 10.1016/j.nmd.2020.03.001. PMID: 32327287
Gillett JG, Lichtwark GA, Boyd RN, Barber LA
Arch Phys Med Rehabil 2018 May;99(5):900-906.e1. Epub 2018 Feb 10 doi: 10.1016/j.apmr.2018.01.020. PMID: 29438658
Borress RS, Maccabee P, Har-El G
Am J Otolaryngol 2007 Sep-Oct;28(5):321-4. doi: 10.1016/j.amjoto.2006.10.003. PMID: 17826533
Gefen A
IEEE Trans Neural Syst Rehabil Eng 2001 Dec;9(4):333-7. doi: 10.1109/7333.1000112. PMID: 12018645

Clinical prediction guides

Khadilkar SV, Chaudhari AD, Singla MB, Dastur RS, Gaitonde PS, Bhutada AG, Hegde MR
Muscle Nerve 2021 Feb;63(2):199-203. Epub 2020 Nov 28 doi: 10.1002/mus.27117. PMID: 33197058
Wojciechowski E, Sman A, Cornett K, Raymond J, Refshauge K, Menezes MP, Burns J; FAST Study Group
Gait Posture 2017 Jul;56:89-94. Epub 2017 May 8 doi: 10.1016/j.gaitpost.2017.05.005. PMID: 28527386
Tozza S, Aceto MG, Pisciotta C, Bruzzese D, Iodice R, Santoro L, Manganelli F
Gait Posture 2016 Sep;49:353-357. Epub 2016 Jul 28 doi: 10.1016/j.gaitpost.2016.07.183. PMID: 27491052
Sackley C, Disler PB, Turner-Stokes L, Wade DT, Brittle N, Hoppitt T
Cochrane Database Syst Rev 2009 Jul 8;(3):CD003908. doi: 10.1002/14651858.CD003908.pub3. PMID: 19588347
Gefen A
IEEE Trans Neural Syst Rehabil Eng 2001 Dec;9(4):333-7. doi: 10.1109/7333.1000112. PMID: 12018645

Recent systematic reviews

Conde RM, Senem I, Dos Santos M, de Lima Osório F, Marques Júnior W
J Peripher Nerv Syst 2023 Jun;28(2):169-178. Epub 2023 Apr 24 doi: 10.1111/jns.12548. PMID: 37060329
Sackley C, Disler PB, Turner-Stokes L, Wade DT, Brittle N, Hoppitt T
Cochrane Database Syst Rev 2009 Jul 8;(3):CD003908. doi: 10.1002/14651858.CD003908.pub3. PMID: 19588347
Sackley C, Disler PB, Turner-Stokes L, Wade DT
Cochrane Database Syst Rev 2007 Apr 18;(2):CD003908. doi: 10.1002/14651858.CD003908.pub2. PMID: 17443532

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