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Spastic paraplegia

MedGen UID:
20882
Concept ID:
C0037772
Disease or Syndrome
Synonyms: Paraplegia, Spastic; Paraplegias, Spastic; Spastic Paraplegia; Spastic Paraplegias
SNOMED CT: Spastic paraplegia (192967009)
 
HPO: HP:0001258

Definition

Progressive spasticity of the lower limbs with exaggerated deep tendon reflexes and Babinski sign classified as pure (with spasticity as the only manifestation) and complicated (with brain abnormalities and mental retardation) forms which are further subdivided into several categories according to their genetic and clinical characteristics. It is involved in numerous syndromic entities. spastic paraplegia 1 (SPG1) (OMIM 312900) Synonym: X-linked complicated spastic paraplegia (SPPX1) Spastic paraplegia, transmitted as an X-linked trait, with neurological complications involving the cerebellum, cerebral cortex, and optic nerves. Severe mental retardation is a constant feature. spastic paraplegia 2 (SPG2) (OMIM 312920) Synonyms: Goldblatt syndrome X-linked uncomplicated spastic paraplegia (SPPX2) Spastic paraplegia, transmitted as an X-linked trait, with nystagmus, optic atrophy, intellectual handicap, and mild ataxia of the upper limbs. spastic paraplegia 3 (SPG3) (OMIM 182600) Synonyms: Strumpell disease Strumpell familial spastic paraplegia Strumpell-Lorrain syndrome von Strumpell syndrome A slowly progressive familial disease, transmitted as an autosomal dominant trait, with lower limb spasticity, gait difficulties, and weakness. Neurological changes involve the lateral cortical tracts and fasciculus gracilis. Some patients exhibit ataxia and neurogenic bladder. spastic paraplegia 4 (SPG4) (OMIM 182601) An uncomplicated form of SPG2 transmitted as an autosomal dominant trait and marked mainly by progressive spasticity of the lower limbs. spastic paraplegia-epilepsy-mental retardation (SPERM) syndrome (OMIM 182610) A syndrome with incomplete penetrance and variable expresivity with progressive weakness and spasticity of the lower limbs, epilepsy, and mental retardation. spastic paraplegia-sensorineural deafness-mental retardation-progressive nephropathy syndrome (OMIM 182690) A complicated form, transmitted as an autosomal dominant trait, with variable spasticity of the lower limbs, sensorineural deafness, delayed mental development, and progressive nephropathy. spastic paraplegia-amyotrophy of hands syndrome (OMIM 182700) Synonyms: Silver syndrome spastic paraplegia-amyotrophy of hands syndrome Spastic paraplegia transmitted, as an autosomal dominant trait, with amyotrophic changes in the upper limbs. spastic paraplegia-extrapyramidal signs syndrome (OMIM 182800) Spastic paraplegia associated with extrapyramidal signs and transmitted as an autosomal dominant trait. spastic paraplegia-neuropathy-poikiloderma syndrome (OMIM 182815) Spastic paraplegia associated with demyelinating peripheral neuropathy, poikiloderma, and loss of eyebrows and eyelashes which is transmitted as an autosomal dominant trait. spastic paraplegia-precocious puberty syndrome (OMIM 182820) Spastic paraplegia with Leydig cell hypoplasia, precocious puberty, brisk leg reflexes, dysarthria, and mild mental retardation which is transmitted as an autosomal dominant trait. spastic paraplegia-optic atrophy-dementia syndrome (OMIM 182830) Spastic paraplegia with optic atrophy, constricted visual fields, and early dementia, which is transmitted as an autosomal dominant trait. spastic paraplegia-retinal degeneration syndrome (OMIM 270700) Synonym: familial spastic paraplegia with retinal degeneration recessive spastic paraplegia with retinal degeneration Spastic paraplegia, transmitted as an autosomal recessive trait, with retinal degeneration and dull mentality. spastic paraplegia-brachydactyly E syndrome (OMIM 270710) Spastic paraplegia ,transmitted as an autosomal recessive trait, with brachydactyly type E, cone-shaped epiphyses, abnormal finger metaphyses, dysarthria, and low-normal intelligence. spastic paraplegia-pigmentary abnormalities syndrome (OMIM 270750) Spastic paraplegia, transmitted as an autosomal recessive trait, with abnormal pigmentation (mainly crural hypopigmentation, pigmented nevi, and depigmented hair), progressive spastic paraparesis, and cerebellar ataxia. hereditary spastic paraplegia (HSP) (OMIM 270800) Synonym: paraplegia spastica hereditaria Spastic paraplegia transmitted as an autosomal recessive trait. Neurological involvement includes pyramidal disorders, dysarthria, impaired vibratory sense, and dysfunction of the glossopharyngeal (ninth), vagus (tenth), and hypoglossal (twelfth) nerves. Mental retardation and visual disorders occur in some cases. spastic paraplegia-epileptic myoclonus syndrome (OMIM 270805) Synonym: hereditary spastic paraplegia-epileptic myoclonus syndrome Spastic paraplegia, transmitted as an autosomal recessive trait, with epileptic myoclonus, muscle atrophy, mental retardation or dullness, ataxia, and hearing loss. spastic paresis-glaucoma-mental retardation syndrome (OMIM 270850) Synonym: spastic paresis-glaucoma-mental retardation syndrome Spastic paraplegia with glaucoma and speech and mental retardation. Transmitted as an autosomal recessive trait with parental consanguinity. spastic athetotic paraplegia (OMIM 312890) Synonym: Baar-Gabriel syndrome Spastic paraplegia, transmitted as an X-linked trait, with athetosis, mental retardation and occasional grand mal epilepsy and myoclonus. [from MCA/MR]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVSpastic paraplegia

Conditions with this feature

Laurence-Moon syndrome
MedGen UID:
44078
Concept ID:
C0023138
Disease or Syndrome
PNPLA6 disorders span a phenotypic continuum characterized by variable combinations of cerebellar ataxia; upper motor neuron involvement manifesting as spasticity and/or brisk reflexes; chorioretinal dystrophy associated with variable degrees of reduced visual function; and hypogonadotropic hypogonadism (delayed puberty and lack of secondary sex characteristics). The hypogonadotropic hypogonadism occurs either in isolation or as part of anterior hypopituitarism (growth hormone, thyroid hormone, or gonadotropin deficiencies). Common but less frequent features are peripheral neuropathy (usually of axonal type manifesting as reduced distal reflexes, diminished vibratory sensation, and/or distal muscle wasting); hair anomalies (long eyelashes, bushy eyebrows, or scalp alopecia); short stature; and impaired cognitive functioning (learning disabilities in children; deficits in attention, visuospatial abilities, and recall in adults). Some of these features can occur in distinct clusters on the phenotypic continuum: Boucher-Neuhäuser syndrome (cerebellar ataxia, chorioretinal dystrophy, and hypogonadotropic hypogonadism); Gordon Holmes syndrome (cerebellar ataxia, hypogonadotropic hypogonadism, and – to a variable degree – brisk reflexes); Oliver-McFarlane syndrome (trichomegaly, chorioretinal dystrophy, short stature, intellectual disability, and hypopituitarism); Laurence-Moon syndrome; and spastic paraplegia type 39 (SPG39) (upper motor neuron involvement, peripheral neuropathy, and sometimes reduced cognitive functioning and/or cerebellar ataxia).
Waardenburg syndrome type 3
MedGen UID:
86948
Concept ID:
C0079661
Disease or Syndrome
Waardenburg syndrome type 3 is an auditory-pigmentary syndrome characterized by pigmentary abnormalities of the hair, skin, and eyes; congenital sensorineural hearing loss; presence of 'dystopia canthorum,' the lateral displacement of the ocular inner canthi; and upper limb abnormalities (reviews by Read and Newton, 1997 and Pingault et al., 2010). WS type 3 is also referred to as 'Klein-Waardenburg syndrome' (Gorlin et al., 1976). Clinical Variability of Waardenburg Syndrome Types 1-4 Waardenburg syndrome has been classified into 4 main phenotypes. Type I Waardenburg syndrome (WS1; 193500) is characterized by pigmentary abnormalities of the hair, including a white forelock and premature graying; pigmentary changes of the iris, such as heterochromia iridis and brilliant blue eyes; congenital sensorineural hearing loss; and 'dystopia canthorum.' WS type II (WS2) is distinguished from type I by the absence of dystopia canthorum. WS type III has dystopia canthorum and is distinguished by the presence of upper limb abnormalities. WS type IV (WS4; 277580), also known as Waardenburg-Shah syndrome, has the additional feature of Hirschsprung disease (reviews by Read and Newton, 1997 and Pingault et al., 2010).
Adrenoleukodystrophy
MedGen UID:
57667
Concept ID:
C0162309
Disease or Syndrome
X-linked adrenoleukodystrophy (X-ALD) affects the nervous system white matter and the adrenal cortex. Three main phenotypes are seen in affected males: The childhood cerebral form manifests most commonly between ages four and eight years. It initially resembles attention-deficit disorder or hyperactivity; progressive impairment of cognition, behavior, vision, hearing, and motor function follow the initial symptoms and often lead to total disability within six months to two years. Most individuals have impaired adrenocortical function at the time that neurologic disturbances are first noted. Adrenomyeloneuropathy (AMN) manifests most commonly in an individual in his twenties or middle age as progressive stiffness and weakness of the legs, sphincter disturbances, sexual dysfunction, and often, impaired adrenocortical function; all symptoms are progressive over decades. "Addison disease only" presents with primary adrenocortical insufficiency between age two years and adulthood and most commonly by age 7.5 years, without evidence of neurologic abnormality; however, some degree of neurologic disability (most commonly AMN) usually develops by middle age. More than 20% of female carriers develop mild-to-moderate spastic paraparesis in middle age or later. Adrenal function is usually normal.
X-linked hydrocephalus syndrome
MedGen UID:
75552
Concept ID:
C0265216
Disease or Syndrome
L1 syndrome involves a phenotypic spectrum ranging from severe to mild and includes three clinical phenotypes: X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS). MASA (mental retardation [intellectual disability], aphasia [delayed speech], spastic paraplegia [shuffling gait], adducted thumbs) syndrome including X-linked complicated hereditary spastic paraplegia type 1. X-linked complicated corpus callosum agenesis. Males with HSAS are born with severe hydrocephalus, adducted thumbs, and spasticity; intellectual disability is severe. In less severely affected males, hydrocephalus may be subclinically present and documented only because of developmental delay; intellectual disability ranges from mild (IQ: 50-70) to moderate (IQ: 30-50). It is important to note that all phenotypes can be observed in affected individuals within the same family.
Homocarnosinosis
MedGen UID:
75703
Concept ID:
C0268632
Disease or Syndrome
Homocarnosinosis is a metabolic defect characterised by progressive spastic diplegia, intellectual deficit and retinitis pigmentosa. This extremely rare disorder has been reported in only one family, namely a woman and three of her children. The latter showed progressive spastic diplegia, mental retardation and retinitis pigmentosa but their mother was symptom free. It is therefore uncertain whether there is a relationship between the biochemical defect and the clinical symptoms. Inheritance in the reported family seems to be autosomal dominant.
Troyer syndrome
MedGen UID:
97950
Concept ID:
C0393559
Disease or Syndrome
Troyer syndrome is characterized by progressive spastic paraparesis, dysarthria, pseudobulbar palsy, distal amyotrophy, short stature, and subtle skeletal abnormalities. Most affected children exhibit delays in walking and speech and difficulty in managing oral secretions, followed by increased lower-limb spasticity and slow deterioration in both gait and speech. Mild cerebellar signs are common. The most severely affected individuals have choreoathetosis. Emotional lability / difficulty in controlling emotions and affective disorders, such as inappropriate euphoria and/or crying, are frequently described. Life expectancy is normal.
Allan-Herndon-Dudley syndrome
MedGen UID:
208645
Concept ID:
C0795889
Disease or Syndrome
Allan-Herndon-Dudley syndrome (AHDS), an X-linked disorder, is characterized in males by neurologic findings (hypotonia and feeding difficulties in infancy, developmental delay / intellectual disability ranging from mild to profound) and later-onset pyramidal signs, extrapyramidal findings (dystonia, choreoathetosis, paroxysmal movement disorder, hypokinesia, masked facies), and seizures, often with drug resistance. Additional findings can include dysthyroidism (manifest as poor weight gain, reduced muscle mass, and variable cold intolerance, sweating, elevated heart rate, and irritability) and pathognomonic thyroid test results. Most heterozygous females are not clinically affected but may have minor thyroid test abnormalities.
MASA syndrome
MedGen UID:
162894
Concept ID:
C0795953
Disease or Syndrome
L1 syndrome involves a phenotypic spectrum ranging from severe to mild and includes three clinical phenotypes: X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS). MASA (mental retardation [intellectual disability], aphasia [delayed speech], spastic paraplegia [shuffling gait], adducted thumbs) syndrome including X-linked complicated hereditary spastic paraplegia type 1. X-linked complicated corpus callosum agenesis. Males with HSAS are born with severe hydrocephalus, adducted thumbs, and spasticity; intellectual disability is severe. In less severely affected males, hydrocephalus may be subclinically present and documented only because of developmental delay; intellectual disability ranges from mild (IQ: 50-70) to moderate (IQ: 30-50). It is important to note that all phenotypes can be observed in affected individuals within the same family.
Hereditary spastic paraplegia 23
MedGen UID:
167094
Concept ID:
C0796019
Disease or Syndrome
Spastic paraplegia-23 (SPG23) is an autosomal recessive neurologic disorder characterized by childhood-onset spastic paraplegia resulting in gait difficulties and associated with pigmentary abnormalities, including premature graying of the hair and vitiligo-like or hyperpigmented skin lesions. Some patients may also have a peripheral neuropathy (summary by Lee et al., 2017).
Hereditary spastic paraplegia 9A
MedGen UID:
322007
Concept ID:
C1832669
Disease or Syndrome
Autosomal dominant spastic paraplegia-9A is a neurologic disorder characterized by onset of slowly progressive spasticity mainly affecting the lower limbs. The age at onset usually ranges from adolescence to adulthood, and patients have gait difficulties, motor neuropathy, and dysarthria. Additional variable features include cerebellar signs, cataract, pes cavus, and urinary urgency (summary by Coutelier et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant spastic paraplegia, see SPG3A (182600).
Dystonia 9
MedGen UID:
371427
Concept ID:
C1832855
Disease or Syndrome
The phenotypic spectrum of glucose transporter type 1 deficiency syndrome (Glut1 DS) is now known to be a continuum that includes the classic phenotype as well as paroxysmal exercise-induced dyskinesia and epilepsy (previously known as dystonia 18 [DYT18]) and paroxysmal choreoathetosis with spasticity (previously known as dystonia 9 [DYT9]), atypical childhood absence epilepsy, myoclonic astatic epilepsy, and paroxysmal non-epileptic findings including intermittent ataxia, choreoathetosis, dystonia, and alternating hemiplegia. The classic phenotype is characterized by infantile-onset seizures, delayed neurologic development, acquired microcephaly, and complex movement disorders. Seizures in classic early-onset Glut1 DS begin before age six months. Several seizure types occur: generalized tonic or clonic, focal, myoclonic, atypical absence, atonic, and unclassified. In some infants, apneic episodes and abnormal episodic eye-head movements similar to opsoclonus may precede the onset of seizures. The frequency, severity, and type of seizures vary among affected individuals and are not related to disease severity. Cognitive impairment, ranging from learning disabilities to severe intellectual disability, is typical. The complex movement disorder, characterized by ataxia, dystonia, and chorea, may occur in any combination and may be continuous, paroxysmal, or continual with fluctuations in severity influenced by environmental factors such as fasting or with infectious stress. Symptoms often improve substantially when a ketogenic diet is started.
Spastic paraplegia, optic atrophy, and neuropathy
MedGen UID:
324411
Concept ID:
C1836010
Disease or Syndrome
Spastic paraplegia, optic atrophy, and neuropathy (SPOAN) is an autosomal recessive neurodegenerative disorder characterized by early-onset progressive spastic paraplegia resulting in loss of independent ambulation in the teenage years. Additional features include optic atrophy, later onset of sensorimotor peripheral neuropathy, and progressive joint contractures; cognition remains intact (summary by Melo et al., 2015).
Spastic paraplegia 28, autosomal recessive
MedGen UID:
332174
Concept ID:
C1836295
Disease or Syndrome
Spastic paraplegia-29 (SPG28) is an autosomal recessive neurodegenerative disorder characterized by early-onset, slowly progressive lower-limb spasticity resulting in walking difficulties. Some patients also have distal sensory impairment (summary by Tesson et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see 270800.
Hereditary spastic paraplegia 26
MedGen UID:
373138
Concept ID:
C1836632
Disease or Syndrome
SPG26 is an autosomal recessive form of complicated spastic paraplegia characterized by onset in the first 2 decades of life of gait abnormalities due to lower limb spasticity and muscle weakness. Some patients have upper limb involvement. Additional features include intellectual disability, peripheral neuropathy, dysarthria, cerebellar signs, extrapyramidal signs, and cortical atrophy. The disorder is slowly progressive (summary by Boukhris et al., 2013). For a discussion of genetic heterogeneity of autosomal recessive SPG, see SPG5A (270800).
Spastic paraplegia 27, autosomal recessive
MedGen UID:
373203
Concept ID:
C1836899
Disease or Syndrome
Autosomal recessive spastic paraplegia type 27 is a rare, pure or complex hereditary spastic paraplegia characterized by a variable onset of slowly progressive lower limb spasticity, hyperreflexia and extensor plantar responses, that may be associated with sensorimotor polyneuropathy, decreased vibration sense, lower limb distal muscle wasting, dysarthria and mild to moderate intellectual disability.
Hereditary spastic paraplegia 6
MedGen UID:
324965
Concept ID:
C1838192
Disease or Syndrome
A rare form of hereditary spastic paraplegia which usually presents in late adolescence or early adulthood as a pure phenotype of lower limb spasticity with hyperreflexia and extensor plantar responses, as well as mild bladder disturbances and pes cavus. Rarely, it can present as a complex phenotype with additional manifestations including epilepsy, variable peripheral neuropathy and/or memory impairment.
Fryns macrocephaly
MedGen UID:
373933
Concept ID:
C1838281
Disease or Syndrome
A rare syndrome with features of multiple congenital anomalies with macrocephaly (of post-natal onset), large anterior fontanelle, progressive complex spastic paraplegia, coarse facial features (broad and high forehead, deeply set eyes, short philtrum with thin upper lip, large mouth and prominent incisors), seizures, and intellectual deficit of varying severity. Inheritance appears to be autosomal recessive.
Hereditary spastic paraplegia 2
MedGen UID:
374177
Concept ID:
C1839264
Disease or Syndrome
PLP1 disorders of central nervous system myelin formation include a range of phenotypes from Pelizaeus-Merzbacher disease (PMD) to spastic paraplegia 2 (SPG2). PMD typically manifests in infancy or early childhood with nystagmus, hypotonia, and cognitive impairment; the findings progress to severe spasticity and ataxia. Life span is shortened. SPG2 manifests as spastic paraparesis with or without CNS involvement and usually normal life span. Intrafamilial variation of phenotypes can be observed, but the signs are usually fairly consistent within families. Heterozygous females may manifest mild-to-moderate signs of the disease.
Optic atrophy--spastic paraplegia syndrome
MedGen UID:
326914
Concept ID:
C1839565
Disease or Syndrome
Mental retardation with spastic paraplegia
MedGen UID:
374293
Concept ID:
C1839727
Disease or Syndrome
Kallmann syndrome with spastic paraplegia
MedGen UID:
333437
Concept ID:
C1839911
Disease or Syndrome
Hereditary spastic paraplegia 24
MedGen UID:
334784
Concept ID:
C1843569
Disease or Syndrome
A very rare, pure form of spastic paraplegia characterized by an onset in infancy of lower limb spasticity associated with gait disturbances, scissor gait, tiptoe walking, clonus and increased deep tendon reflexes. Mild upper limb involvement may occasionally also be associated.
Spastic paraplegia, ataxia, and mental retardation
MedGen UID:
336010
Concept ID:
C1843661
Disease or Syndrome
Cerebral sclerosis, diffuse, scholz type
MedGen UID:
335049
Concept ID:
C1844884
Disease or Syndrome
Hereditary spastic paraplegia 16
MedGen UID:
375796
Concept ID:
C1846046
Disease or Syndrome
Spastic paraplegias (SPGs) are a genetically heterogeneous group of neurologic disorders characterized by progressive weakness and spasticity of the legs. Complicated SPGs are accompanied by additional neurologic symptoms such as cerebellar ataxia, sensory loss, mental retardation, nystagmus, and optic atrophy (summary by Steinmuller et al., 1997). A locus for spastic paraplegia-16 has been mapped to Xq11.2-q23 (Steinmuller et al., 1997). For a discussion of genetic heterogeneity of X-linked spastic paraplegia, see 303350.
Hereditary spastic paraplegia 7
MedGen UID:
339552
Concept ID:
C1846564
Disease or Syndrome
Spastic paraplegia 7 (SPG7) is characterized by insidiously progressive bilateral leg weakness and spasticity. Most affected individuals have decreased vibration sense and cerebellar signs. Onset is mostly in adulthood, although symptoms may start as early as age 11 years and as late as age 72 years. Additional features including ataxia (gait and limbs), spastic dysarthria, dysphagia, pale optic disks, ataxia, nystagmus, strabismus, ptosis, hearing loss, motor and sensory neuropathy, amyotrophy, scoliosis, pes cavus, and urinary sphincter disturbances may be observed.
Hereditary spastic paraplegia 19
MedGen UID:
335494
Concept ID:
C1846685
Disease or Syndrome
A pure form of hereditary spastic paraplegia characterized by a slowly progressive and relatively benign spastic paraplegia presenting in adulthood with spastic gait, lower limb hyperreflexia, extensor plantar responses, bladder dysfunction (urinary urgency and/or incontinence), and mild sensory and motor peripheral neuropathy.
Kufor-Rakeb syndrome
MedGen UID:
338281
Concept ID:
C1847640
Disease or Syndrome
Kufor-Rakeb syndrome is a rare autosomal recessive form of juvenile-onset atypical Parkinson disease (PARK9) associated with supranuclear gaze palsy, spasticity, and dementia. Some patients have neuroradiologic evidence of iron deposition in the basal ganglia, indicating that the pathogenesis of PARK9 can be considered among the syndromes of neurodegeneration with brain iron accumulation (NBIA; see 234200) (summary by Bruggemann et al., 2010). For a phenotypic description and a discussion of genetic heterogeneity of Parkinson disease (PD), see 168600. Biallelic mutation in the ATP13A2 gene also causes autosomal recessive spastic paraplegia-78 (SPG78; 617225), an adult-onset neurodegenerative disorder with overlapping features. Patients with SPG78 have later onset and prominent spasticity, but rarely parkinsonism. Loss of ATP13A2 function results in a multidimensional spectrum of neurologic features reflecting various regions of the brain and nervous system, including cortical, pyramidal, extrapyramidal, brainstem, cerebellar, and peripheral (summary by Estrada-Cuzcano et al., 2017).
X-linked immunoneurologic disorder
MedGen UID:
341162
Concept ID:
C1848144
Disease or Syndrome
A syndrome with characteristics of immune deficiency and neurological disorders in females and neonatal death in males. The syndrome has been described in only one family with nine affected individuals (five males and four females) spanning two generations. Symptomatic females present slowly progressive proximal muscle weakness, leg hyperreflexia, pes cavus, increased muscle tone in the legs, poor bladder function, static reduced night vision and frequent sinopulmonary infections associated with IgG2 deficiency. Males present with low birth weight and severe hypotonia that leads to death in the neonatal period. The gene locus has been mapped to Xq26-qter.
Spastic paresis, glaucoma, and mental retardation
MedGen UID:
376520
Concept ID:
C1849113
Disease or Syndrome
Spastic paraplegia-glaucoma-intellectual disability syndrome is characterized by progressive spastic paraplegia, glaucoma and intellectual deficit. It has been described in two families. The second described sibship was born to consanguineous parents. The mode of inheritance is autosomal recessive.
Hereditary spastic paraplegia 5A
MedGen UID:
376521
Concept ID:
C1849115
Disease or Syndrome
Spastic paraplegia-5A (SPG5A) is an autosomal recessive neurologic disorder with a wide phenotypic spectrum. Some patients have pure spastic paraplegia affecting only gait, whereas others may have a complicated phenotype with additional manifestations, including optic atrophy or cerebellar ataxia (summary by Arnoldi et al., 2012). The hereditary spastic paraplegias (SPG) are a group of clinically and genetically diverse disorders characterized by progressive, usually severe, lower extremity spasticity; see reviews of Fink et al. (1996) and Fink (1997). Inheritance is most often autosomal dominant (see 182600), but X-linked (see 303350) and autosomal recessive forms also occur. Genetic Heterogeneity of Autosomal Recessive Spastic Paraplegia Autosomal recessive forms of SPG include SPG7 (607259), caused by mutation in the paraplegin gene (602783) on chromosome 16q24; SPG9B (616586), caused by mutation in the ALDH18A1 gene (138250) on 10q24; SPG11 (604360), caused by mutation in the spatacsin gene (610844) on 15q21; SPG15 (270700), caused by mutation in the ZFYVE26 gene (612012) on 14q24; SPG18 (611225), caused by mutation in the ERLIN2 gene (611605) on 8p11; SPG20 (275900), caused by mutation in the spartin gene (607111) on 13q12; SPG21 (248900), caused by mutation in the maspardin gene (608181) on 15q21; SPG26 (609195), caused by mutation in the B4GALNT1 gene (601873) on 12q13; SPG28 (609340), caused by mutation in the DDHD1 gene (614603) on 14q22; SPG30 (610357), caused by mutation in the KIF1A gene (601255) on 2q37; SPG35 (612319), caused by mutation in the FA2H gene (611026) on 16q23; SPG39 (612020), caused by mutation in the PNPLA6 gene (603197) on 19p13.3; SPG43 (615043), caused by mutation in the C19ORF12 gene (614297) on 19q12; SPG44 (613206), caused by mutation in the GJC2 gene (608803) on 1q42; SPG45 (613162), caused by mutation in the NT5C2 gene (600417) on 10q24; SPG46 (614409), caused by mutation in the GBA2 gene (609471) on 9p13; SPG48 (613647), caused by mutation in the KIAA0415 gene (613653) on 7p22.1; SPG54 (615033), caused by mutation in the DDHD2 gene (615003) on 8p11; SPG55 (615035), caused by mutation in the MTRFR gene on 12q24; SPG56 (615030), caused by mutation in the CYP2U1 gene (610670) on 4q25; SPG57 (615658), caused by mutation in the TFG gene (602498) on 3q12; SPG61 (615685), caused by mutation in the ARL6IP1 gene (607669) on 1p12; SPG62 (615681), caused by mutation in the ERLIN1 gene on 10q24; SPG63 (615686), caused by mutation in the AMPD2 gene (102771) on 1p13; SPG64 (615683), caused by mutation in the ENTPD1 gene (601752) on 10q24; SPG72 (615625), caused by mutation in the REEP2 gene (609347) on 5q31; SPG74 (616451), caused by mutation in the IBA57 gene (615316) on 1q42; SPG75 (616680), caused by mutation in the MAG gene (159460) on 19q13; SPG76 (616907), caused by mutation in the CAPN1 gene (114220) on 11q13; SPG77 (617046), caused by mutation in the FARS2 gene (611592) on 6p25; SPG78 (617225), caused by mutation in the ATP13A2 gene (610513) on 1p36; SPG79 (615491), caused by mutation in the UCHL1 gene (191342) on 4p13; SPG81 (618768), caused by mutation in the SELENOI gene (607915) on 2p23; SPG82 (618770), caused by mutation in the PCYT2 gene (602679) on 17q25; and SPG83 (619027), caused by mutation in the HPDL gene (618994) on 1p34. Additional autosomal recessive forms of SPG have been mapped to chromosomes 3q (SPG14; 605229), 13q14 (SPG24; 607584), 6q (SPG25; 608220), and 10q22 (SPG27; 609041). A disorder that was formerly designated SPG49 has been reclassified as hereditary sensory and autonomic neuropathy-9 with developmental delay (HSAN9; 615031).
Hereditary spastic paraplegia 15
MedGen UID:
341387
Concept ID:
C1849128
Disease or Syndrome
Spastic paraplegia 15 (SPG15), typically an early-onset complex hereditary spastic paraplegia, is characterized by progressive spasticity that begins in the lower extremities and is associated with several manifestations resulting from central and peripheral nervous system dysfunction. While onset of spasticity is typically in mid- to late childhood or adolescence (i.e., between ages 5 and 18 years), other manifestations, such as developmental delay or learning disability, may be present earlier, often preceding motor involvement. Individuals with adult onset have also been reported.
Adult polyglucosan body disease
MedGen UID:
342338
Concept ID:
C1849722
Disease or Syndrome
Most individuals with classic GBE1 adult polyglucosan body disease (GBE1-APBD) present after age 40 years with unexplained progressive neurogenic bladder, gait difficulties (i.e., spasticity and weakness) from mixed upper and lower motor neuron involvement, sensory loss predominantly in the distal lower extremities, autonomic dysfunction (associated with orthostatic hypotension and constipation), and mild cognitive difficulties (often executive dysfunction). Some affected individuals without classic GBE1-APBD have atypical phenotypes including Alzheimer disease-like dementia and axonal neuropathy, stroke-like episodes, and diaphragmatic failure; others may have a history of infantile liver disease.
Giant axonal neuropathy 1
MedGen UID:
376775
Concept ID:
C1850386
Disease or Syndrome
GAN-related neurodegeneration comprises a phenotypic continuum ranging from severe (sometimes called classic giant axonal neuropathy) to milder pure early-onset peripheral motor and sensory neuropathies. The classic giant axonal neuropathy phenotype typically manifests as an infantile-onset neurodegenerative disorder, starting as a severe peripheral motor and sensory neuropathy and evolving into central nervous system impairment (intellectual disability, seizures, cerebellar signs, and pyramidal tract signs). Most affected individuals become wheelchair dependent in the second decade of life and eventually bedridden with severe polyneuropathy, ataxia, and dementia. Death usually occurs in the third decade. At the milder end of the spectrum are predominantly motor and sensory neuropathies (with little to no CNS involvement) that overlap with the axonal form of Charcot-Marie-Tooth neuropathies.
Neuropathy, hereditary sensory, with spastic paraplegia, autosomal recessive
MedGen UID:
342492
Concept ID:
C1850395
Disease or Syndrome
This syndrome is characterized by the association of an axonal sensory and autonomic neuropathy with spastic paraplegia.
Spastic paraplegia 31, autosomal dominant
MedGen UID:
377858
Concept ID:
C1853247
Disease or Syndrome
The first signs and symptoms of spastic paraplegia type 31 usually appear before age 20 or after age 30. An early feature is difficulty walking due to spasticity and weakness, which typically affect both legs equally. People with spastic paraplegia type 31 can also experience progressive muscle wasting (amyotrophy) in the lower limbs, exaggerated reflexes (hyperreflexia), a decreased ability to feel vibrations, reduced bladder control, and high-arched feet (pes cavus). As the condition progresses, some individuals require walking support.\n\nSpastic paraplegia type 31 is one of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by progressive muscle stiffness (spasticity) and the development of paralysis of the lower limbs (paraplegia) caused by degeneration of nerve cells that trigger muscle movement (motor neurons). Hereditary spastic paraplegias are divided into two types: pure and complicated. The pure types involve only the lower limbs, while the complicated types also involve the upper limbs and other areas of the body, including the brain. Spastic paraplegia type 31 is usually a pure hereditary spastic paraplegia, although a few complicated cases have been reported.
Spastic paraplegia 33, autosomal dominant
MedGen UID:
339943
Concept ID:
C1853251
Disease or Syndrome
Any hereditary spastic paraplegia in which the cause of the disease is a mutation in the ZFYVE27 gene.
Hereditary spastic paraplegia 13
MedGen UID:
344289
Concept ID:
C1854467
Disease or Syndrome
A rare hereditary spastic paraplegia characterized by progressive spastic paraplegia with pyramidal signs in the lower limbs, decreased vibration sense, and increased reflexes in the upper limbs.
Hereditary spastic paraplegia 14
MedGen UID:
343157
Concept ID:
C1854568
Disease or Syndrome
Autosomal recessive spastic paraplegia type 14 is a rare, complex hereditary spastic paraplegia characterized by adulthood-onset of slowly progressive spastic paraplegia of lower limbs presenting with spastic gait, hyperreflexia, and mild lower limb hypertonicity associated with mild intellectual disability, visual agnosia, short and long-term memory deficiency and mild distal motor neuropathy. Bilateral pes cavus and extensor plantar responses are also associated.
Metaphyseal modeling abnormality, skin lesions, and spastic paraplegia
MedGen UID:
343282
Concept ID:
C1855164
Disease or Syndrome
Mast syndrome
MedGen UID:
343325
Concept ID:
C1855346
Disease or Syndrome
Mast syndrome is an autosomal recessive complicated form of hereditary spastic paraplegia in which progressive spastic paraparesis is associated in more advanced cases with cognitive decline, dementia, and other neurologic abnormalities. Symptom onset usually occurs in adulthood, and the disorder is progressive with variable severity. Brain imaging shows thinning of the corpus callosum. The disorder occurs with high frequency in the Old Order Amish (summary by Simpson et al., 2003). For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800).
Limb defects, distal transverse, with mental retardation and spasticity
MedGen UID:
340888
Concept ID:
C1855501
Disease or Syndrome
Intellectual disability-spasticity-ectrodactyly syndrome is a rare intellectual disability syndrome characterized by severe intellectual disability, spastic paraplegia (with wasting of the lower limbs) and distal transverse defects of the limbs (e.g. ectrodactyly, syndactyly, clinodactyly of the hands and/or feet).
Pyruvate dehydrogenase E3-binding protein deficiency
MedGen UID:
343383
Concept ID:
C1855553
Disease or Syndrome
Pyruvate dehydrogenase deficiency is characterized by the buildup of a chemical called lactic acid in the body and a variety of neurological problems. Signs and symptoms of this condition usually first appear shortly after birth, and they can vary widely among affected individuals. The most common feature is a potentially life-threatening buildup of lactic acid (lactic acidosis), which can cause nausea, vomiting, severe breathing problems, and an abnormal heartbeat. People with pyruvate dehydrogenase deficiency usually have neurological problems as well. Most have delayed development of mental abilities and motor skills such as sitting and walking. Other neurological problems can include intellectual disability, seizures, weak muscle tone (hypotonia), poor coordination, and difficulty walking. Some affected individuals have abnormal brain structures, such as underdevelopment of the tissue connecting the left and right halves of the brain (corpus callosum), wasting away (atrophy) of the exterior part of the brain known as the cerebral cortex, or patches of damaged tissue (lesions) on some parts of the brain. Because of the severe health effects, many individuals with pyruvate dehydrogenase deficiency do not survive past childhood, although some may live into adolescence or adulthood.
Hereditary spastic paraplegia 29
MedGen UID:
346682
Concept ID:
C1857855
Disease or Syndrome
A complex form of hereditary spastic paraplegia characterized by a spastic paraplegia presenting in adolescence, associated with the additional manifestations of sensorial hearing impairment due to auditory neuropathy and persistent vomiting due to a hiatal or paraesophageal hernia.
Hereditary spastic paraplegia 12
MedGen UID:
347618
Concept ID:
C1858106
Disease or Syndrome
Spastic paraplegia-12 is an autosomal dominant neurodegenerative disorder characterized by lower limb spasticity and hyperreflexia, resulting in walking difficulties. Some patients may have urinary symptoms and distal sensory impairment. The age at onset is variable and can range from childhood to adulthood (summary by Montenegro et al., 2012). For a general description and a discussion of genetic heterogeneity of autosomal dominant spastic paraplegia, see SPG3A (182600).
Spastic paraplegia 11, autosomal recessive
MedGen UID:
388073
Concept ID:
C1858479
Disease or Syndrome
Spastic paraplegia 11 (SPG11) is characterized by progressive spasticity and weakness of the lower limbs frequently associated with the following: mild intellectual disability with learning difficulties in childhood and/or progressive cognitive decline; peripheral neuropathy; pseudobulbar involvement; and increased reflexes in the upper limbs. Less frequent findings include: cerebellar signs (ataxia, nystagmus, saccadic pursuit); retinal degeneration; pes cavus; scoliosis; and parkinsonism with characteristic brain MRI features that include thinning of the corpus callosum. Onset occurs mainly during infancy or adolescence (range: age 1-31 years) and in rare cases as late as age 60 years. Most affected individuals become wheelchair bound one or two decades after disease onset.
Hereditary spastic paraplegia 10
MedGen UID:
349003
Concept ID:
C1858712
Disease or Syndrome
Spastic paraplegia-10 (SPG10) is an autosomal dominant neurologic disorder with variable manifestations. Some patients have onset of a 'pure' spastic paraplegia, with lower limb spasticity, hyperreflexia, extensor plantar responses, and variable involvement of the upper limbs beginning in childhood or young adulthood. Some patients show distal sensory impairment, which can be part of the 'pure' phenotype. However, some patients also show an axonal sensorimotor peripheral neuropathy with distal sensory impairment and distal muscle atrophy reminiscent of Charcot-Marie-Tooth disease type 2 (see, e.g., CMT2A, 118210). Rarely, patients with KIF5A mutations may have additional neurologic features, including parkinsonism or cognitive decline, consistent with a 'complicated' phenotype. Spastic paraplegia and peripheral neuropathy in isolation may represent extreme ends of the phenotypic spectrum of KIF5A mutations (summary by Goizet et al., 2009 and Crimella et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant spastic paraplegia, see SPG3A (182600).
Amyotrophic dystonic paraplegia
MedGen UID:
354871
Concept ID:
C1862956
Disease or Syndrome
Hereditary spastic paraplegia 8
MedGen UID:
400359
Concept ID:
C1863704
Disease or Syndrome
Hereditary spastic paraplegia 8 (SPG8) is a slowly progressive pure spastic paraplegia of the lower limbs (i.e., pyramidal signs including hyperreflexia, spasticity, and occasionally clonus without other neurologic findings). Some affected individuals have urinary urgency that usually becomes apparent at the same time as the spasticity. Onset is between ages ten and 59 years. Affected individuals often become wheelchair dependent. While intra- and interfamilial phenotypic variability is high, SPG8 is typically more severe than other types of hereditary spastic paraplegia.
Spastic paraplegia and Evans syndrome
MedGen UID:
355764
Concept ID:
C1866619
Disease or Syndrome
Spastic paraplegia, optic atrophy, and dementia
MedGen UID:
356630
Concept ID:
C1866849
Disease or Syndrome
Spastic paraplegia-precocious puberty syndrome
MedGen UID:
401096
Concept ID:
C1866850
Disease or Syndrome
Spastic paraplegia-precocious puberty syndrome is a complex form of hereditary spastic paraplegia characterized by the onset of progressive spastic paraplegia associated with precocious puberty (due to Leydig cell hyperplasia) in childhood (at the age of 2 years). Moderate intellectual disability was also reported. There have been no further descriptions in the literature since 1983.
Spastic paraplegia-neuropathy-poikiloderma syndrome
MedGen UID:
355814
Concept ID:
C1866851
Disease or Syndrome
A complex form of hereditary spastic paraplegia characterized by spastic paraplegia, demyelinating peripheral sensorimotor neuropathy, poikiloderma (manifesting with loss of eyebrows and eyelashes in childhood in addition to delicate, smooth, and wasted skin) and distal amyotrophy (presenting after puberty). There have been no further descriptions in the literature since 1992.
Spastic paraplegia with associated extrapyramidal signs
MedGen UID:
355815
Concept ID:
C1866852
Disease or Syndrome
Spastic paraplegia, sensorineural deafness, mental retardation, and progressive nephropathy
MedGen UID:
355816
Concept ID:
C1866853
Disease or Syndrome
Spastic paraplegia-nephritis-deafness syndrome is a complex form of hereditary spastic paraplegia characterized by progressive, variable spastic paraplegia associated with bilateral sensorineural deafness, intellectual disability, and progressive nephropathy. There have been no further descriptions in the literature since 1988.
Spastic paraplegia-epilepsy-intellectual disability syndrome
MedGen UID:
356631
Concept ID:
C1866854
Disease or Syndrome
Spastic paraplegia 4, autosomal dominant
MedGen UID:
401097
Concept ID:
C1866855
Disease or Syndrome
Spastic paraplegia 4 (SPG4; also known as SPAST-HSP) is characterized by insidiously progressive bilateral lower-limb gait spasticity. More than 50% of affected individuals have some weakness in the legs and impaired vibration sense at the ankles. Sphincter disturbances are very common. Onset is insidious, mostly in young adulthood, although symptoms may start as early as age one year and as late as age 76 years. Intrafamilial variation is considerable.
Spastic paraplegia 32, autosomal recessive
MedGen UID:
409967
Concept ID:
C1970009
Disease or Syndrome
Autosomal recessive spastic paraplegia type 32 (SPG32) is a rare, complex type of hereditary spastic paraplegia characterized by a slowly progressive spastic paraplegia (with walking difficulties appearing at onset at 6-7 years of age) associated with mild intellectual disability. Brain imaging reveals thin corpus callosum, cortical and cerebellar atrophy, and pontine dysraphia. The SPG32 phenotype has been mapped to a locus on chromosome 14q12-q21.
Ataxia, spastic, 1, autosomal dominant
MedGen UID:
409988
Concept ID:
C1970107
Disease or Syndrome
The hereditary ataxias are a group of genetic disorders characterized by slowly progressive incoordination of gait and often associated with poor coordination of hands, speech, and eye movements. Frequently, atrophy of the cerebellum occurs. In this GeneReview the hereditary ataxias are categorized by mode of inheritance and gene (or chromosome locus) in which pathogenic variants occur.
Spastic paraplegia 42, autosomal dominant
MedGen UID:
393407
Concept ID:
C2675528
Disease or Syndrome
A pure form of hereditary spastic paraplegia characterized by slowly progressive spastic paraplegia of lower extremities with an age of onset ranging from childhood to adulthood and patients presenting with spastic gait, increased tendon reflexes in lower limbs, extensor plantar response, weakness and atrophy of lower limb muscles and, in rare cases, pes cavus. No abnormalities are noted on magnetic resonance imaging.
Spastic paraplegia 38, autosomal dominant
MedGen UID:
436764
Concept ID:
C2676732
Disease or Syndrome
A complex hereditary spastic paraplegia characterized by mild to severe lower limbs spasticity, hyperreflexia, extensor plantar responses, pes cavus and significant wasting and weakness of the small hand muscles. Impaired vibration sensation, temporal lobe epilepsy and cognitive dysfunction were also reported.
Early infantile epileptic encephalopathy 4
MedGen UID:
436917
Concept ID:
C2677326
Disease or Syndrome
STXBP1 encephalopathy with epilepsy is characterized by early-onset encephalopathy with epilepsy (i.e., moderate-to-severe intellectual disability, refractory seizures, and ongoing epileptiform activity). The median age of onset of seizures is six weeks (range 1 day to 13 years). Seizure types can include infantile spasms; generalized tonic-clonic, clonic, or tonic seizures; and myoclonic, focal, atonic, and absence seizures. Epilepsy syndromes can include Ohtahara syndrome, West syndrome, Lennox-Gaustaut syndrome, and Dravet syndrome (not SCN1A-related), classic Rett syndrome (not MECP2-related), and atypical Rett syndrome (not CDKL5-related). The EEG is characterized by focal epileptic activity, burst suppression, hypsarrhythmia, or generalized spike-and-slow waves. Other findings can include abnormal tone, movement disorders (especially ataxia and dystonia), and behavior disorders (including autism spectrum disorder). Feeding difficulties are common.
Spastic paraplegia 34, X-linked
MedGen UID:
437069
Concept ID:
C2677897
Disease or Syndrome
X-linked spastic paraplegia type 34 is a pure form of hereditary spastic paraplegia characterized by late childhood- to early adulthood-onset of slowly progressive spastic paraplegia with spastic gait and lower limb hyperreflexia, brisk tendon reflexes and ankle clonus. Lower limb pain and reduced lower limb vibratory sense is also reported in some older adult patients.
Spastic paraplegia 43, autosomal recessive
MedGen UID:
760531
Concept ID:
C2680446
Disease or Syndrome
Spastic paraplegia-43 (SPG43) is an autosomal recessive neurodegenerative disorder characterized by childhood onset of progressive spasticity affecting the lower and upper limbs (summary by Meilleur et al., 2010). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see 270800.
Mental retardation with spastic paraplegia and palmoplantar hyperkeratosis
MedGen UID:
411554
Concept ID:
C2745996
Disease or Syndrome
This syndrome has characteristics of intellectual deficit, spasticity in the lower limbs (spastic paraplegia), pes cavus deformity of both feet, an abnormal gait, and palmar and plantar hyperkeratosis. It has been reported in four brothers. The mother of the affected boys had normal intelligence, plantar hyperkeratosis and a strong facial resemblance to her retarded sons. Her three daughters were normal. This syndrome most likely an X-linked recessive condition.
Hereditary spastic paraplegia 18
MedGen UID:
442343
Concept ID:
C2749936
Disease or Syndrome
Spastic paraplegia-18 (SPG18) is a severe autosomal recessive neurologic disorder characterized by onset in early childhood of progressive spastic paraplegia resulting in motor disability. Most affected individuals have severe psychomotor retardation. Some may develop significant joint contractures (summary by Alazami et al., 2011 and Yildirim et al., 2011).
Spastic paraplegia 44, autosomal recessive
MedGen UID:
413042
Concept ID:
C2750784
Disease or Syndrome
gene (1q41-q42) encoding the gap junction gamma-2 protein.
Spastic paraplegia 50, autosomal recessive
MedGen UID:
442869
Concept ID:
C2752008
Disease or Syndrome
AP-4-associated hereditary spastic paraplegia (HSP), also known as AP-4 deficiency syndrome, is a group of neurodegenerative disorders characterized by a progressive, complex spastic paraplegia with onset typically in infancy or early childhood. Early-onset hypotonia evolves into progressive lower-extremity spasticity. The majority of children become nonambulatory and usually wheelchair bound. Over time spasticity progresses to involve the upper extremities, resulting in a spastic tetraplegia. Associated complications include dysphagia, contractures, foot deformities, dysregulation of bladder and bowel function, and a pseudobulbar affect. About 50% of affected individuals have seizures. Postnatal microcephaly (usually in the -2SD to -3SD range) is common. All have developmental delay. Speech development is significantly impaired and many affected individuals remain nonverbal. Intellectual disability in older children is usually moderate to severe.
Spastic paraplegia 46, autosomal recessive
MedGen UID:
473687
Concept ID:
C2828721
Disease or Syndrome
Autosomal recessive spastic paraplegia-46 (SPG46) is a neurodegenerative disorder characterized by onset in childhood of slowly progressive spastic paraplegia and cerebellar signs. Some patients have cognitive impairment, cataracts, and cerebral, cerebellar, and corpus callosum atrophy on brain imaging (summary by Boukhris et al., 2010 and Martin et al., 2013). For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800).
Spastic paraplegia 17
MedGen UID:
419034
Concept ID:
C2931276
Disease or Syndrome
The spectrum of BSCL2-related neurologic disorders includes Silver syndrome and variants of Charcot-Marie-Tooth neuropathy type 2, distal hereditary motor neuropathy (dHMN) type V, and spastic paraplegia 17. Features of these disorders include onset of symptoms ranging from the first to the seventh decade, slow disease progression, upper motor neuron involvement (gait disturbance with pyramidal signs ranging from mild to severe spasticity with hyperreflexia in the lower limbs and variable extensor plantar responses), lower motor neuron involvement (amyotrophy of the peroneal muscles and small muscles of the hand), and pes cavus and other foot deformities. Disease severity is variable among and within families.
Hereditary spastic paraplegia 3A
MedGen UID:
419393
Concept ID:
C2931355
Disease or Syndrome
Spastic paraplegia 3A (SPG3A; also known as ATL1-HSP) is characterized by progressive bilateral and mostly symmetric spasticity and weakness of the legs. Compared to other forms of autosomal dominant hereditary spastic paraplegia (HSP), in which diminished vibration sense (caused by degeneration of the corticospinal tracts and dorsal columns) and urinary bladder hyperactivity are present in all affected individuals, these findings occur in a minority of individuals with SPG3A. The average age of onset is four years. More than 80% of reported individuals manifest spastic gait before the end of the first decade of life. Most persons with early-onset ATL1-HSP have a "pure" ("uncomplicated") HSP; however, complicated HSP with axonal motor neuropathy and/or distal amyotrophy with lower motor neuron involvement (Silver syndrome phenotype) have been observed. The rate of progression in ATL1-HSP is slow, and wheelchair dependency or need for a walking aid (cane, walker, or wheelchair) is relatively rare.
Infantile-onset ascending hereditary spastic paralysis
MedGen UID:
419413
Concept ID:
C2931441
Disease or Syndrome
ALS2-related disorder involves retrograde degeneration of the upper motor neurons of the pyramidal tracts and comprises a clinical continuum of the following three phenotypes: Infantile ascending hereditary spastic paraplegia (IAHSP), characterized by onset of spasticity with increased reflexes and sustained clonus of the lower limbs within the first two years of life, progressive weakness and spasticity of the upper limbs by age seven to eight years, and wheelchair dependence in the second decade with progression toward severe spastic tetraparesis and a pseudobulbar syndrome caused by progressive cranial nerve involvement. Juvenile primary lateral sclerosis (JPLS), characterized by upper motor neuron findings of pseudobulbar palsy and spastic quadriplegia without dementia or cerebellar, extrapyramidal, or sensory signs. Juvenile amyotrophic lateral sclerosis (JALS or ALS2), characterized by onset between ages three and 20 years. All affected individuals show a spastic pseudobulbar syndrome (spasticity of speech and swallowing) together with spastic paraplegia. Some individuals are bedridden by age 12 to 50 years.
Hereditary spastic paraplegia 25
MedGen UID:
424835
Concept ID:
C2936860
Disease or Syndrome
Autosomal recessive spastic paraplegia type 25 (SPG25) is a rare, complex type of hereditary spastic paraplegia characterized by adult-onset spastic paraplegia associated with spinal pain that radiates to the upper or lower limbs and is related to disk herniation (with minor spondylosis), as well as mild sensorimotor neuropathy. The SPG25 phenotype has been mapped to a locus on chromosome 6q23-q24.1.
Spastic paraplegia 36, autosomal dominant
MedGen UID:
422457
Concept ID:
C2936879
Disease or Syndrome
A complex form of hereditary spastic paraplegia, characterized by an onset in childhood or adulthood of progressive spastic paraplegia (with spastic gait, spasticity, lower limb weakness, pes cavus and urinary urgency) associated with the additional manifestation of peripheral sensorimotor neuropathy.
Spastic paraplegia 37, autosomal dominant
MedGen UID:
422458
Concept ID:
C2936880
Disease or Syndrome
A pure form of hereditary spastic paraplegia characterized by a childhood- to adulthood-onset of slowly progressive spastic gait, extensor plantar responses, brisk tendon reflexes in arms and legs, decreased vibration sense at ankles and urinary dysfunction. Ankle clonus is also reported in some patients.
Spastic paraplegia 48, autosomal recessive
MedGen UID:
462251
Concept ID:
C3150901
Disease or Syndrome
Spastic paraplegia-48 (SPG48) is an autosomal recessive neurologic disorder characterized by spasticity of the lower limbs resulting in gait difficulties. Most patients have onset in mid- or late-adulthood, although childhood onset has been reported in 1 patient. Additional features may include parkinsonism, urinary incontinence, neuropathy, and mild cognitive impairment (summary by Hirst et al., 2015). For a discussion of genetic heterogeneity of autosomal recessive SPG, see SPG5A (270800).
Spastic paraplegia 51, autosomal recessive
MedGen UID:
462406
Concept ID:
C3151056
Disease or Syndrome
AP-4-associated hereditary spastic paraplegia (HSP), also known as AP-4 deficiency syndrome, is a group of neurodegenerative disorders characterized by a progressive, complex spastic paraplegia with onset typically in infancy or early childhood. Early-onset hypotonia evolves into progressive lower-extremity spasticity. The majority of children become nonambulatory and usually wheelchair bound. Over time spasticity progresses to involve the upper extremities, resulting in a spastic tetraplegia. Associated complications include dysphagia, contractures, foot deformities, dysregulation of bladder and bowel function, and a pseudobulbar affect. About 50% of affected individuals have seizures. Postnatal microcephaly (usually in the -2SD to -3SD range) is common. All have developmental delay. Speech development is significantly impaired and many affected individuals remain nonverbal. Intellectual disability in older children is usually moderate to severe.
Spastic paraplegia 47, autosomal recessive
MedGen UID:
481368
Concept ID:
C3279738
Disease or Syndrome
AP-4-associated hereditary spastic paraplegia (HSP), also known as AP-4 deficiency syndrome, is a group of neurodegenerative disorders characterized by a progressive, complex spastic paraplegia with onset typically in infancy or early childhood. Early-onset hypotonia evolves into progressive lower-extremity spasticity. The majority of children become nonambulatory and usually wheelchair bound. Over time spasticity progresses to involve the upper extremities, resulting in a spastic tetraplegia. Associated complications include dysphagia, contractures, foot deformities, dysregulation of bladder and bowel function, and a pseudobulbar affect. About 50% of affected individuals have seizures. Postnatal microcephaly (usually in the -2SD to -3SD range) is common. All have developmental delay. Speech development is significantly impaired and many affected individuals remain nonverbal. Intellectual disability in older children is usually moderate to severe.
Spastic paraplegia 52, autosomal recessive
MedGen UID:
481373
Concept ID:
C3279743
Disease or Syndrome
AP-4-associated hereditary spastic paraplegia (HSP), also known as AP-4 deficiency syndrome, is a group of neurodegenerative disorders characterized by a progressive, complex spastic paraplegia with onset typically in infancy or early childhood. Early-onset hypotonia evolves into progressive lower-extremity spasticity. The majority of children become nonambulatory and usually wheelchair bound. Over time spasticity progresses to involve the upper extremities, resulting in a spastic tetraplegia. Associated complications include dysphagia, contractures, foot deformities, dysregulation of bladder and bowel function, and a pseudobulbar affect. About 50% of affected individuals have seizures. Postnatal microcephaly (usually in the -2SD to -3SD range) is common. All have developmental delay. Speech development is significantly impaired and many affected individuals remain nonverbal. Intellectual disability in older children is usually moderate to severe.
Aicardi Goutieres syndrome 2
MedGen UID:
483677
Concept ID:
C3489724
Disease or Syndrome
Most characteristically, Aicardi-Goutières syndrome (AGS) manifests as an early-onset encephalopathy that usually, but not always, results in severe intellectual and physical disability. A subgroup of infants with AGS present at birth with abnormal neurologic findings, hepatosplenomegaly, elevated liver enzymes, and thrombocytopenia, a picture highly suggestive of congenital infection. Otherwise, most affected infants present at variable times after the first few weeks of life, frequently after a period of apparently normal development. Typically, they demonstrate the subacute onset of a severe encephalopathy characterized by extreme irritability, intermittent sterile pyrexias, loss of skills, and slowing of head growth. Over time, as many as 40% develop chilblain skin lesions on the fingers, toes, and ears. It is becoming apparent that atypical, sometimes milder, cases of AGS exist, and thus the true extent of the phenotype associated with pathogenic variants in the AGS-related genes is not yet known.
Spastic paraplegia 35
MedGen UID:
501249
Concept ID:
C3496228
Disease or Syndrome
Fatty acid hydroxylase-associated neurodegeneration (FAHN) is characterized early in the disease course by central nervous system involvement including corticospinal tract involvement (spasticity), mixed movement disorder (ataxia/dystonia), and eye findings (optic atrophy, oculomotor abnormalities), and later in the disease course by progressive intellectual impairment and seizures. With disease progression, dystonia and spasticity compromise the ability to ambulate, leading to wheelchair dependence. Life expectancy is variable. FAHN is considered to be a subtype of neurodegeneration with brain iron accumulation (NBIA).
Spastic paraplegia 53, autosomal recessive
MedGen UID:
761340
Concept ID:
C3539494
Disease or Syndrome
SPG53 is an autosomal recessive neurologic disorder characterized by onset in infancy of delayed motor development progressing to upper and lower limb spasticity with impaired walking. Affected individuals also show mild to moderate cognitive impairment (summary by Zivony-Elboum et al., 2012).
Spastic paraplegia 54, autosomal recessive
MedGen UID:
761341
Concept ID:
C3539495
Disease or Syndrome
Spastic paraplegia-54 is a complicated form of spastic paraplegia, a neurodegenerative disorder affecting fibers of the corticospinal tract. Affected individuals have delayed psychomotor development, intellectual disability, and early-onset spasticity of the lower limbs. Brain MRI shows a thin corpus callosum and periventricular white matter lesions. Brain magnetic resonance spectroscopy shows an abnormal lipid peak (summary by Schuurs-Hoeijmakers et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see 270800.
Spastic paraplegia 55, autosomal recessive
MedGen UID:
761342
Concept ID:
C3539506
Disease or Syndrome
gene (12q24.31) encoding probable peptide chain release factor C12orf65, mitochondrial.
Spastic paraplegia 56, autosomal recessive
MedGen UID:
761343
Concept ID:
C3539507
Disease or Syndrome
SPG56 is an autosomal recessive neurodegenerative disorder characterized by early-onset progressive lower-limb spasticity resulting in walking difficulties. Upper limbs are often also affected, and some patients may have a subclinical axonal neuropathy (summary by Tesson et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see 270800.
Spastic paraplegia 49, autosomal recessive
MedGen UID:
762260
Concept ID:
C3542549
Disease or Syndrome
Hereditary sensory and autonomic neuropathy type IX with developmental delay (HSAN9) is an autosomal recessive neurodevelopmental and neurodegenerative disorder. Clinical features include global developmental delay and intellectual disability, axial and appendicular hypotonia, dysarthria, and an abnormal gait that is often described as ataxic. Other features may include peripheral neuropathy, hyporeflexia, and autonomic dysfunction (summary by Neuser et al., 2021). For a discussion of genetic heterogeneity of hereditary sensory and autonomic neuropathy, see HSAN1 (162400).
Pontocerebellar hypoplasia, type 7
MedGen UID:
767140
Concept ID:
C3554226
Disease or Syndrome
Pontocerebellar hypoplasia type 7 is a severe neurologic condition characterized by delayed psychomotor development, hypotonia, breathing abnormalities, and gonadal abnormalities (summary by Anderson et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1 (607596).
Lissencephaly 5
MedGen UID:
767571
Concept ID:
C3554657
Disease or Syndrome
Lissencephaly-5 (LIS5) is an autosomal recessive brain malformation characterized by cobblestone changes in the cortex, more severe in the posterior region, and subcortical band heterotopia. Affected individuals have hydrocephalus, seizures, and severely delayed psychomotor development (Radmanesh et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of lissencephaly, see LIS1 (607432).
Spastic paraplegia 57, autosomal recessive
MedGen UID:
811490
Concept ID:
C3714897
Disease or Syndrome
gene (3q12.2) encoding protein TFG, which is thought to play a role in ER microtubular architecture and function.
Spastic paraplegia 79, autosomal recessive
MedGen UID:
815995
Concept ID:
C3809665
Disease or Syndrome
Spastic paraplegia-79 (SPG79) is an autosomal recessive progressive neurologic disorder characterized by onset of spastic paraplegia and optic atrophy in the first decade of life. Additional features are variable, but may include peripheral neuropathy, cerebellar ataxia, and cognitive impairment (summary by Rydning et al., 2017). For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800).
Spastic paraplegia 72, autosomal recessive
MedGen UID:
816490
Concept ID:
C3810160
Disease or Syndrome
Hereditary spastic paraplegia-72 is a pure form of spastic paraplegia with onset of difficulty walking and stiff legs associated with hyperreflexia and extensor plantar responses in early childhood. The disorder is slowly progressive, and some patients develop the need for assistance in walking. Some patients may have pes cavus or sphincter disturbances. Cognition, speech, and ocular function are normal (summary by Esteves et al., 2014). For a discussion of genetic heterogeneity of autosomal dominant spastic paraplegia, see SPG3A (182600), and for autosomal recessive spastic paraplegia, see SPG5A (270800).
Spastic paraplegia 64, autosomal recessive
MedGen UID:
816619
Concept ID:
C3810289
Disease or Syndrome
gene (10q24.1), encoding ectonucleoside triphosphate diphosphohydrolase 1.
Spastic paraplegia 61, autosomal recessive
MedGen UID:
816624
Concept ID:
C3810294
Disease or Syndrome
gene (16p12-p11.2) encoding the ADP-ribosylation factor-like protein 6-interacting protein 1.
Spastic paraplegia 63, autosomal recessive
MedGen UID:
816625
Concept ID:
C3810295
Disease or Syndrome
gene (1p13.3) encoding AMP deaminase 2.
Spastic paraplegia 41, autosomal dominant
MedGen UID:
854815
Concept ID:
C3888208
Disease or Syndrome
A pure form of hereditary spastic paraplegia characterized by onset in adolescence or early adulthood of slowly progressive spastic paraplegia, proximal muscle weakness of the lower extremities and small hand muscles, hyperreflexia, spastic gait and mild urinary compromise.
Spastic paraplegia 45, autosomal recessive
MedGen UID:
854816
Concept ID:
C3888209
Disease or Syndrome
Autosomal recessive spastic paraplegia type 45 is a rare, pure or complex form of hereditary spastic paraplegia characterized by onset in infancy of progressive lower limb spasticity, abnormal gait, increased deep tendon reflexes and extensor plantar responses, that may be associated with intellectual disability. Additional signs, such as contractures in the lower limbs, amyotrophy, clubfoot and optic atrophy, have also been reported.
Spastic paraplegia 9b, autosomal recessive
MedGen UID:
909058
Concept ID:
C4225272
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).
Spastic paraplegia 74, autosomal recessive
MedGen UID:
908839
Concept ID:
C4225322
Disease or Syndrome
Spastic paraplegia-74 (SPG74) is an autosomal recessive neurologic disorder characterized by onset of slowly progressive lower limb spasticity, optic atrophy, and peripheral neuropathy in the first decade (summary by Lossos et al., 2015). For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800).
Spastic paraplegia 73, autosomal dominant
MedGen UID:
905874
Concept ID:
C4225387
Disease or Syndrome
A pure form of hereditary spastic paraplegia characterized by adult onset of crural spastic paraparesis, hyperreflexia, extensor plantar responses, proximal muscle weakness, mild muscle atrophy, decreased vibration sensation at ankles, and mild urinary dysfunction. Foot deformities have been reported to eventually occur in some patients. No abnormalities are noted on brain magnetic resonance imaging and peripheral nerve conduction velocity studies.
Spastic paraplegia, intellectual disability, nystagmus, and obesity
MedGen UID:
924883
Concept ID:
C4284592
Disease or Syndrome
Spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO) is an autosomal dominant neurologic disorder characterized by rapid growth in infancy, global developmental delay, spastic paraplegia, variable ophthalmologic defects, and dysmorphic facial features (summary by Josifova et al., 2016).
Spastic paraplegia 78, autosomal recessive
MedGen UID:
934629
Concept ID:
C4310662
Disease or Syndrome
Autosomal recessive spastic paraplegia-78 is an adult-onset neurodegenerative disorder characterized predominantly by spasticity and muscle weakness of the lower limbs, resulting in gait difficulties and loss of ambulation in some patients. Affected individuals also have cerebellar signs, such as dysarthria, oculomotor disturbances, and limb and gait ataxia; brain imaging shows cerebellar atrophy. Some patients may have mild cognitive impairment or frank dementia. The phenotype is highly variable (summary by Estrada-Cuzcano et al., 2017). Biallelic mutation in the ATP13A2 gene also causes Kufor-Rakeb syndrome (KRS; 606693), a neurodegenerative disorder with overlapping features. Patients with KRS have earlier onset and prominent parkinsonism. Loss of ATP13A2 function results in a multidimensional spectrum of neurologic features reflecting various regions of the brain and nervous system, including cortical, pyramidal, extrapyramidal, brainstem, cerebellar, and peripheral (summary by Estrada-Cuzcano et al., 2017).
Spastic paraplegia 77, autosomal recessive
MedGen UID:
934717
Concept ID:
C4310750
Disease or Syndrome
The spectrum of FARS2 deficiency ranges from the infantile-onset phenotype, characterized by epileptic encephalopathy with lactic acidosis and poor prognosis (70% of affected individuals), to the later-onset phenotype, characterized by spastic paraplegia, less severe neurologic manifestations, and longer survival (30% of affected individuals). To date FARS2 deficiency has been reported in 37 individuals from 25 families. Infantile-onset phenotype. Seizures are difficult to control and may progress quickly at an early age to intractable seizures with frequent status epilepticus; some children have hypsarrhythmia on EEG. All have developmental delay; most are nonverbal and unable to walk. Feeding difficulties are common. More than half of affected children die in early childhood. Later-onset phenotype. All affected individuals have spastic paraplegia manifested by weakness, spasticity, and exaggerated reflexes of the lower extremities associated with walking difficulties; some have developmental delay/intellectual disability; some have brief seizures that resolve over time.
Spastic paraplegia 76, autosomal recessive
MedGen UID:
934767
Concept ID:
C4310800
Disease or Syndrome
Spastic paraplegia-76 is an autosomal recessive neurologic disorder characterized by young-adult onset of slowly progressive spasticity of the lower limbs resulting in gait difficulties. Most affected individuals have upper limb involvement and additional features such as foot deformities and dysarthria. Cognition is unaffected (summary by Gan-Or et al., 2016). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800).
Peroxisome biogenesis disorder 10b
MedGen UID:
1379481
Concept ID:
C4479254
Disease or Syndrome
Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures
MedGen UID:
1633724
Concept ID:
C4693816
Disease or Syndrome
Spastic paraplegia 80, autosomal dominant
MedGen UID:
1682111
Concept ID:
C5193084
Disease or Syndrome
Spastic paraplegia-80 (SPG80) is an autosomal dominant juvenile-onset neurologic disorder characterized by onset of progressive spasticity and hyperreflexia affecting mainly the lower limbs and resulting in difficulty walking or loss of independent ambulation, sometimes as early as the second decade. Some patients may have cerebellar signs and mild cognitive impairment, but most have a pure form of the disorder (summary by Farazi Fard et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant spastic paraplegia, see SPG3A (182600).
Neurodevelopmental disorder with cerebellar hypoplasia and spasticity
MedGen UID:
1684815
Concept ID:
C5231415
Disease or Syndrome
Spastic paraplegia 30, autosomal recessive
MedGen UID:
1710020
Concept ID:
C5235139
Disease or Syndrome
Spastic paraplegia-30 (SPG30) is a neurologic disorder characterized by onset of slowly progressive spastic paraplegia in the first or second decades of life. Affected individuals have unsteady spastic gait and hyperreflexia of the lower limbs. Some patients have a 'pure' form of the disorder, limited to spastic paraplegia, whereas others may have a 'complicated' form that includes cognitive dysfunction, learning disabilities, or behavioral abnormalities, peripheral sensorimotor neuropathy, urinary sphincter problems, and/or cerebellar atrophy with thin corpus callosum on brain imaging. The phenotypic features represent a spectrum of abnormalities of the central, peripheral, and autonomic nervous system (summary by Pennings et al., 2020). For a discussion of genetic heterogeneity of autosomal dominant spastic paraplegia, see SPG3A (182600). For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800).
Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities
MedGen UID:
1736667
Concept ID:
C5436628
Disease or Syndrome
Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities (NEDSWMA) is an autosomal recessive disorder characterized by impaired psychomotor development apparent in infancy. Affected individuals show poor overall growth, progressive microcephaly, and axial hypotonia, with later onset of spasticity. The disorder is progressive. Some patients show normal early development, but later have regression of motor, cognitive, and language skills. More variable features include seizures, joint contractures, ocular disturbances, episodic respiratory failure, and nonspecific dysmorphic facial features. The intellectual impairment is variable, ranging from poor visual contact with inability to walk or speak to milder intellectual disability with the ability to say some words. Brain imaging shows variable white matter abnormalities, including thin corpus callosum and poor myelination (summary by Husain et al., 2020).
Spastic paraplegia 83, autosomal recessive
MedGen UID:
1759445
Concept ID:
C5436637
Disease or Syndrome
Autosomal recessive spastic paraplegia-83 (SPG83) is a neurologic disorder characterized by progressive lower limb spasticity resulting in gait instability. Patients develop symptoms in the second decade, consistent with juvenile onset. Some patients may have myalgia or mild dysarthria, but the phenotype is considered to be a pure type of SPG with no additional neurologic abnormalities (summary by Husain et al., 2020). For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800).
Autosomal recessive congenital ichthyosis 4A
MedGen UID:
371355
Concept ID:
C1832550
Congenital Abnormality
Autosomal recessive congenital ichthyosis (ARCI) encompasses several forms of nonsyndromic ichthyosis. Although most neonates with ARCI are collodion babies, the clinical presentation and severity of ARCI may vary significantly, ranging from harlequin ichthyosis, the most severe and often fatal form, to lamellar ichthyosis (LI) and (nonbullous) congenital ichthyosiform erythroderma (CIE). These phenotypes are now recognized to fall on a continuum; however, the phenotypic descriptions are clinically useful for clarification of prognosis and management. Infants with harlequin ichthyosis are usually born prematurely and are encased in thick, hard, armor-like plates of cornified skin that severely restrict movement. Life-threatening complications in the immediate postnatal period include respiratory distress, feeding problems, and systemic infection. Collodion babies are born with a taut, shiny, translucent or opaque membrane that encases the entire body and lasts for days to weeks. LI and CIE are seemingly distinct phenotypes: classic, severe LI with dark brown, plate-like scale with no erythroderma and CIE with finer whiter scale and underlying generalized redness of the skin. Affected individuals with severe involvement can have ectropion, eclabium, scarring alopecia involving the scalp and eyebrows, and palmar and plantar keratoderma. Besides these major forms of nonsyndromic ichthyosis, a few rare subtypes have been recognized, such as bathing suit ichthyosis, self-improving collodion ichthyosis, or ichthyosis-prematurity syndrome.

Recent clinical studies

Etiology

Zeigelboim BS, José MR, Santos GJBD, Severiano MIR, Teive HAG, Stechman-Neto J, Santos RS, de Araújo CM, Cavalcante-Leão BL
PLoS One 2021;16(4):e0249095. Epub 2021 Apr 1 doi: 10.1371/journal.pone.0249095. PMID: 33793609Free PMC Article
Romagnoli ER, Akly MP, Miquelini LA, Funes JA, Besada CH
Neuroradiol J 2021 Feb;34(1):42-44. Epub 2020 Sep 4 doi: 10.1177/1971400920953820. PMID: 32885726Free PMC Article
Yu W, Jin H, Deng J, Nan D, Huang Y
BMC Med Genet 2020 Jun 3;21(1):123. doi: 10.1186/s12881-020-01053-7. PMID: 32493220Free PMC Article
De la Casa-Fages B, Fernández-Eulate G, Gamez J, Barahona-Hernando R, Morís G, García-Barcina M, Infante J, Zulaica M, Fernández-Pelayo U, Muñoz-Oreja M, Urtasun M, Olaskoaga A, Zelaya V, Jericó I, Saez-Villaverde R, Catalina I, Sola E, Martínez-Sáez E, Pujol A, Ruiz M, Schlüter A, Spinazzola A, Muñoz-Blanco JL, Grandas F, Holt I, Álvarez V, López de Munaín A
Mov Disord 2019 Oct;34(10):1547-1561. Epub 2019 Aug 21 doi: 10.1002/mds.27812. PMID: 31433872
Lin X, Su HZ, Dong EL, Lin XH, Zhao M, Yang C, Wang C, Wang J, Chen YJ, Yu H, Xu J, Ma LX, Xiong ZQ, Wang N, Chen WJ
Brain 2019 Aug 1;142(8):2238-2252. doi: 10.1093/brain/awz158. PMID: 31203368

Diagnosis

Zeigelboim BS, José MR, Santos GJBD, Severiano MIR, Teive HAG, Stechman-Neto J, Santos RS, de Araújo CM, Cavalcante-Leão BL
PLoS One 2021;16(4):e0249095. Epub 2021 Apr 1 doi: 10.1371/journal.pone.0249095. PMID: 33793609Free PMC Article
Du J
J Clin Neurosci 2021 Mar;85:67-71. Epub 2021 Jan 15 doi: 10.1016/j.jocn.2020.11.036. PMID: 33581793
Romagnoli ER, Akly MP, Miquelini LA, Funes JA, Besada CH
Neuroradiol J 2021 Feb;34(1):42-44. Epub 2020 Sep 4 doi: 10.1177/1971400920953820. PMID: 32885726Free PMC Article
Yu W, Jin H, Deng J, Nan D, Huang Y
BMC Med Genet 2020 Jun 3;21(1):123. doi: 10.1186/s12881-020-01053-7. PMID: 32493220Free PMC Article
de Freitas JL, Rezende Filho FM, Sallum JMF, França MC Jr, Pedroso JL, Barsottini OGP
J Neurol Sci 2020 Feb 15;409:116620. Epub 2019 Dec 6 doi: 10.1016/j.jns.2019.116620. PMID: 31865189

Therapy

Zeigelboim BS, José MR, Santos GJBD, Severiano MIR, Teive HAG, Stechman-Neto J, Santos RS, de Araújo CM, Cavalcante-Leão BL
PLoS One 2021;16(4):e0249095. Epub 2021 Apr 1 doi: 10.1371/journal.pone.0249095. PMID: 33793609Free PMC Article
Diniz de Lima F, Faber I, Servelhere KR, Bittar MFR, Martinez ARM, Piovesana LG, Martins MP, Martins CR Jr, Benaglia T, de Sá Carvalho B, Nucci A, França MC Jr
Mov Disord 2021 Jul;36(7):1654-1663. Epub 2021 Feb 17 doi: 10.1002/mds.28523. PMID: 33595142
van Lith BJH, den Boer J, van de Warrenburg BPC, Weerdesteyn V, Geurts AC
J Rehabil Med 2019 Jun 18;51(6):434-441. doi: 10.2340/16501977-2556. PMID: 30968942
Marelli C, Lamari F, Rainteau D, Lafourcade A, Banneau G, Humbert L, Monin ML, Petit E, Debs R, Castelnovo G, Ollagnon E, Lavie J, Pilliod J, Coupry I, Babin PJ, Guissart C, Benyounes I, Ullmann U, Lesca G, Thauvin-Robinet C, Labauge P, Odent S, Ewenczyk C, Wolf C, Stevanin G, Hajage D, Durr A, Goizet C, Mochel F
Brain 2018 Jan 1;141(1):72-84. doi: 10.1093/brain/awx297. PMID: 29228183
Schöls L, Rattay TW, Martus P, Meisner C, Baets J, Fischer I, Jägle C, Fraidakis MJ, Martinuzzi A, Saute JA, Scarlato M, Antenora A, Stendel C, Höflinger P, Lourenco CM, Abreu L, Smets K, Paucar M, Deconinck T, Bis DM, Wiethoff S, Bauer P, Arnoldi A, Marques W, Jardim LB, Hauser S, Criscuolo C, Filla A, Züchner S, Bassi MT, Klopstock T, De Jonghe P, Björkhem I, Schüle R
Brain 2017 Dec 1;140(12):3112-3127. doi: 10.1093/brain/awx273. PMID: 29126212Free PMC Article

Prognosis

Tanti M, Cairns D, Mirza N, McCann E, Young C
Neurogenetics 2020 Oct;21(4):305-308. Epub 2020 Jun 5 doi: 10.1007/s10048-020-00619-0. PMID: 32500351
Yu W, Jin H, Deng J, Nan D, Huang Y
BMC Med Genet 2020 Jun 3;21(1):123. doi: 10.1186/s12881-020-01053-7. PMID: 32493220Free PMC Article
Chen X, Liu J, Wei QQ, Ou RW, Cao B, Yuan X, Hou Y, Zhang L, Shang H
BMC Neurol 2020 Jan 3;20(1):2. doi: 10.1186/s12883-019-1593-y. PMID: 31900114Free PMC Article
Zhu Z, Zhang C, Zhao G, Liu Q, Zhong P, Zhang M, Tang W, Zhan F, Tian W, Wang Y, Yin K, Huang X, Jiang J, Liu X, Liu S, Zhou H, Luan X, Tang H, Wang Y, Chen S, Cao L
Parkinsonism Relat Disord 2019 Dec;69:125-133. Epub 2019 Nov 6 doi: 10.1016/j.parkreldis.2019.11.007. PMID: 31751864
Wakil SM, Alhissi S, Al Dossari H, Alqahtani A, Shibin S, Melaiki BT, Finsterer J, Al-Hashem A, Bohlega S, Alazami AM
BMC Med Genet 2019 Jul 4;20(1):119. doi: 10.1186/s12881-019-0851-6. PMID: 31272422Free PMC Article

Clinical prediction guides

Du J
J Clin Neurosci 2021 Mar;85:67-71. Epub 2021 Jan 15 doi: 10.1016/j.jocn.2020.11.036. PMID: 33581793
Yu W, Jin H, Deng J, Nan D, Huang Y
BMC Med Genet 2020 Jun 3;21(1):123. doi: 10.1186/s12881-020-01053-7. PMID: 32493220Free PMC Article
de Freitas JL, Rezende Filho FM, Sallum JMF, França MC Jr, Pedroso JL, Barsottini OGP
J Neurol Sci 2020 Feb 15;409:116620. Epub 2019 Dec 6 doi: 10.1016/j.jns.2019.116620. PMID: 31865189
De la Casa-Fages B, Fernández-Eulate G, Gamez J, Barahona-Hernando R, Morís G, García-Barcina M, Infante J, Zulaica M, Fernández-Pelayo U, Muñoz-Oreja M, Urtasun M, Olaskoaga A, Zelaya V, Jericó I, Saez-Villaverde R, Catalina I, Sola E, Martínez-Sáez E, Pujol A, Ruiz M, Schlüter A, Spinazzola A, Muñoz-Blanco JL, Grandas F, Holt I, Álvarez V, López de Munaín A
Mov Disord 2019 Oct;34(10):1547-1561. Epub 2019 Aug 21 doi: 10.1002/mds.27812. PMID: 31433872
Marelli C, Lamari F, Rainteau D, Lafourcade A, Banneau G, Humbert L, Monin ML, Petit E, Debs R, Castelnovo G, Ollagnon E, Lavie J, Pilliod J, Coupry I, Babin PJ, Guissart C, Benyounes I, Ullmann U, Lesca G, Thauvin-Robinet C, Labauge P, Odent S, Ewenczyk C, Wolf C, Stevanin G, Hajage D, Durr A, Goizet C, Mochel F
Brain 2018 Jan 1;141(1):72-84. doi: 10.1093/brain/awx297. PMID: 29228183

Recent systematic reviews

Du J
J Clin Neurosci 2021 Mar;85:67-71. Epub 2021 Jan 15 doi: 10.1016/j.jocn.2020.11.036. PMID: 33581793
Erfanian Omidvar M, Torkamandi S, Rezaei S, Alipoor B, Omrani MD, Darvish H, Ghaedi H
J Neurol 2021 Jun;268(6):2065-2082. Epub 2019 Nov 19 doi: 10.1007/s00415-019-09633-1. PMID: 31745725
Zhang HJ, Silva N, Solli E, Ayala AC, Tomycz L, Christie C, Mazzola CA
Childs Nerv Syst 2020 Dec;36(12):3147-3152. Epub 2020 May 6 doi: 10.1007/s00381-020-04624-4. PMID: 32377828
Lohkamp LN, Coulter I, Ibrahim GM
Childs Nerv Syst 2020 Jul;36(7):1357-1365. Epub 2020 Apr 16 doi: 10.1007/s00381-020-04601-x. PMID: 32300873
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320

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