{"Name":"Hereditary spastic paraplegia 4","DiseaseID__c":"GARD:0004925","id":4925,"encodedName":"hereditary-spastic-paraplegia-4","IsDeleted":false,"Disease_Name_Full__c":"Hereditary spastic paraplegia 4","Xref_IDs__c":"723820001; C129981; C1866855; C536865; DOID:0110792; MEDGEN:401097; MONDO:0008438; OMIM:182601; ORPHA:100985","USA_Estimate__c":"5,000","No_of_Specialist_Tagsa__c":4,"No_of_ClinGen_records__c":0,"No_of_GeneReviews__c":0,"No_of_HHS_records__c":2,"World_Estimate__c":"8,000 to 80,000","No_of_HRSA_records__c":0,"Evidence_Based_Score__c":2,"No_of_Disease_Descriptions__c":5,"Disease_Characteristics_Score__c":8,"No_of_Age_at_Onset__c":4,"Description_Source__c":"MONDO:0008438","Disease_Description__c":"A rare form of hereditary spastic paraplegia with high intrafamilial clinical variability, characterized in most cases as a pure phenotype with an adult onset (mainly the 3rd to 5th decade of life, but that can present at any age) of progressive gait impairment due to bilateral lower-limb spasticity and weakness as well as very mild proximal weakness and urinary urgency. In some cases, a complex phenotype is also reported with additional manifestations including cognitive impairment, cerebellar ataxia, epilepsy and neuropathy. A faster disease progression is noted in patients with a later age of onset.","GARD_Name__c":"Hereditary spastic paraplegia 4","GARD_Synonym__c":"autosomal dominant spastic paraplegia 4; autosomal dominant spastic paraplegia type 4; familial spastic paraplegia autosomal dominant 2; hereditary spastic paraplegia caused by mutation in spast; hereditary spastic paraplegia type 4; spast hereditary spastic paraplegia; spastic paraplegia 4; spastic paraplegia 4, autosomal dominant; spg4","Curated_Disease_Description_Source__c":"GARD:0004925","Curated_Disease_Description__c":"Autosomal dominant spastic paraplegia type 4 (Autosomal dominant SPG4) is the most common type of hereditary spastic paraplegia (HSP) inherited in an autosomal dominant manner. Autosomal dominant SPG4 is characterized by slowly progressive muscle weakness and spasticity (stiff or rigid muscles) in the lower half of the body. In rare cases, individuals may have a more complex form with seizures, ataxia, and dementia. Autosomal dominant SPG4 is caused by genetic changes in the SPAST gene.","Curated_USA_Estimate_Source__c":null,"Curated_USA_Estimate__c":"5,000","Age_at_Onset_Snippet_Text__c":"at a variety of ages","SourceID__c":"ORPHA:100985","Deprecated__c":"No","Disease_Concept_Type__c":"Rare Disease Entity","MONDO_ID__c":"MONDO:0008438","ORPHANET_ID__c":"ORPHA:100985","Replaced_By_ID__c":null,"Display_Spanish_Disease_Name__c":"Paraplejía espástica autosómica dominante tipo 4","Spanish_Description_Source__c":"ORPHA:100985","Spanish_Description__c":"Es una forma de paraparesia espástica hereditaria con alta variabilidad clínica intrafamiliar, caracterizada en la mayoría de los casos como un fenotipo puro de inicio en la edad adulta (principalmente de la tercera a la quinta década de vida, pero que puede presentarse a cualquier edad) con afectación progresiva de la marcha debido a la espasticidad y debilidad bilateral de las extremidades inferiores, así como debilidad proximal muy leve y urgencia urinaria. En algunos casos, también se ha descrito un fenotipo complejo con manifestaciones adicionales que incluyen afectación cognitiva, ataxia cerebelosa, epilepsia y neuropatía. Se observa una progresión más rápida de la enfermedad en pacientes con una edad de inicio más tardía.","Spanish_Disease_Name__c":"paraplejía espástica autosómica dominante tipo 4","Spanish_GARD_Synonym__c":"spg4","Category_Linearization__c":"ORPHA:98006","icd10_id__c":null,"mesh_id__c":null,"omim_id__c":null,"snomed_id__c":null,"umls_id__c":null,"GARD_Disease__c":[{"Curated_Disease_Description__c":"Autosomal dominant spastic paraplegia type 4 (Autosomal dominant SPG4) is the most common type of hereditary spastic paraplegia (HSP) inherited in an autosomal dominant manner. Autosomal dominant SPG4 is characterized by slowly progressive muscle weakness and spasticity (stiff or rigid muscles) in the lower half of the body. In rare cases, individuals may have a more complex form with seizures, ataxia, and dementia. Autosomal dominant SPG4 is caused by genetic changes in the SPAST gene.","Curated_Disease_Description_Source__c":"GARD:0004925","GARD_Synonym__c":"autosomal dominant spastic paraplegia 4; autosomal dominant spastic paraplegia type 4; familial spastic paraplegia autosomal dominant 2; hereditary spastic paraplegia caused by mutation in spast; hereditary spastic paraplegia type 4; spast hereditary spastic paraplegia; spastic paraplegia 4; spastic paraplegia 4, autosomal dominant; spg4","Name":"Hereditary spastic paraplegia 4","Curated_USA_Estimate__c":"5,000","estimateUsa":"5,000"}],"Organization_Supported_Diseases__c":[{"Account_Name__c":"CureSPG4 Foundation","Website__c":"https://www.curespg4.org/"},{"Account_Name__c":"Lilly and Blair Foundation","Website__c":"https://www.lillyandblair.org/"},{"Account_Name__c":"The Maurya Koduri Foundation","Website__c":"https://www.mauryakoduri.org/"},{"Account_Name__c":"Spastic Paraplegia Foundation","Website__c":"https://sp-foundation.org/"}],"GARD_Disease_Tag__c":[{"Tag_Name__c":"Genetics","Tag_Category__c":"Cause;Disease Category;Specialist","category_description":"Genetic diseases affect the DNA, or genetic instructions, which directs how tissues, organs, and body systems function.","curated_tag_name":"Genetic diseases"},{"Tag_Name__c":"Neurology","Tag_Category__c":"Disease Category;Specialist","category_description":"Neurological diseases affect the brain, spinal cord, cranial nerves, autonomic nerves, or other peripheral nerves.","curated_tag_name":"Neurological diseases"},{"Tag_Name__c":"Hereditary Spastic Paraplegia","Tag_Category__c":"Account","curated_tag_name":"Hereditary spastic paraplegia"},{"Tag_Name__c":"Neuromuscular medicine","Tag_Category__c":"Specialist","curated_tag_name":"Neuromuscular medicine"},{"Tag_Name__c":"Pediatrics","Tag_Category__c":"Specialist"}],"Age_At_Onset__c":[{"Age_At_Onset__c":"Adolescent","Provided_By__c":"ORPHA:100985"},{"Age_At_Onset__c":"Adult","Provided_By__c":"ORPHA:100985"},{"Age_At_Onset__c":"Infancy","Provided_By__c":"ORPHA:100985"},{"Age_At_Onset__c":"Childhood","Provided_By__c":"ORPHA:100985"}],"Diagnosis__c":[{"Type__c":"GTR","Curie__c":"MEDGEN:C1866855"}],"External_Identifier_Disease__c":[{"URL__c":"https://raresource.nih.gov/diseases/filter/0004925","Source__c":"RareSource"},{"URL__c":"https://www.ncbi.nlm.nih.gov/books/NBK1160","Source__c":"Gene Review","Xref__c":"NBK1160"},{"URL__c":"https://uts.nlm.nih.gov/uts/umls/concept/C1866855","Source__c":"C1866855","Xref__c":"C1866855"},{"URL__c":"https://browser.ihtsdotools.org/?perspective=full&conceptId1=723820001","Source__c":"C1866855; MONDO:0008438","Xref__c":"723820001"},{"URL__c":"https://www.ncbi.nlm.nih.gov/mesh/C536865","Source__c":"MONDO:0008438","Xref__c":"C536865"},{"URL__c":"https://www.orpha.net/en/disease/detail/100985","Source__c":"C1866855; MONDO:0008438; ORPHA:100985","Xref__c":"ORPHA:100985"},{"URL__c":"https://www.ebi.ac.uk/ols4/ontologies/doid/classes?obo_id=DOID%3A0110792","Source__c":"MONDO:0008438","Xref__c":"DOID:0110792"},{"URL__c":"https://evsexplore.semantics.cancer.gov/evsexplore/concept/ncit/C129981","Source__c":"C1866855; MONDO:0008438","Xref__c":"C129981"},{"URL__c":"https://www.ncbi.nlm.nih.gov/medgen/?term=401097","Source__c":"C1866855","Xref__c":"MEDGEN:401097"},{"URL__c":"https://www.omim.org/entry/182601","Source__c":"C1866855; MONDO:0008438; ORPHA:100985","Xref__c":"OMIM:182601"},{"URL__c":"http://purl.obolibrary.org/obo/MONDO_0008438","Source__c":"GARD:0004925","Xref__c":"MONDO:0008438"},{"URL__c":"https://medlineplus.gov/genetics/condition/spastic-paraplegia-type-4"},{"URL__c":"https://medlineplus.gov/genetics/condition/spastic-paraplegia-type-4","Source__c":"GARD:0004925","Xref__c":"https://medlineplus.gov/genetics/condition/spastic-paraplegia-type-4"}],"GARD_Disease_Gene__c":[{"GeneSymbol__c":"SPAST","GHR_URL__c":"https://medlineplus.gov/genetics/gene/spast","Gene_Type__c":"protein-coding gene","Causal_Gene__c":true}],"Inheritance__c":["Autosomal dominant"],"GARD_Disease_Feature__c":[{"Provided_By__c":"ORPHA:100985","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A decrease in the ability to perceive vibration at the ankles. Clinically, this is usually tested with a tuning fork which vibrates at 128 Hz and is applied to the malleoli of the ankles.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0006938","HPO_Synonym__c":"Decreased vibration sense at ankles; Decreased vibration sense in feet; Impaired vibration sensation at ankles","HPO_Name__c":"Impaired vibration sensation at ankles","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:100985","HPO_Frequency__c":"Uncommon (<1-4%)","Feature__r":{"HPO_Description__c":"The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001249","HPO_Synonym__c":"Intellectual disability; Mental deficiency; Mental retardation; Mental retardation, nonspecific; Mental-retardation; Nonprogressive intellectual disability; Nonprogressive mental retardation","HPO_Name__c":"Intellectual disability","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:100985","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Weakness of the muscles of the legs.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0007340","HPO_Synonym__c":"Leg weakness; Lower extremity weakness; Lower limb muscle weakness; Lower limb weakness; Muscle weakness in lower limbs","HPO_Name__c":"Lower limb muscle weakness","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:100985","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001761","HPO_Synonym__c":"Cavus foot; High-arched foot","HPO_Name__c":"Pes cavus","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:100985","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Spasticity (velocity-dependent increase in tonic stretch reflexes with increased muscle tone and hyperexcitable tendon reflexes) in the muscles of the lower limbs, hips, and pelvis.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002061","HPO_Synonym__c":"Lower extremities spasticity; Lower extremity spasticity; Spastic lower extremities; Spastic lower extremity; Spastic lower limb; Spastic lower limbs; Spasticity in lower extremities; Spasticity in lower extremity; Spasticity in lower limb; Spasticity in lower limbs; Spasticity of lower extremities; Spasticity of lower extremity; Spasticity of lower limb; Spasticity of lower limbs","HPO_Name__c":"Lower limb spasticity","Feature_System__c":"Nervous System; Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:100985","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Abnormal function of a sphincter of the urinary bladder.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002839","HPO_Synonym__c":"Sphincter disturbance; Sphincter disturbances","HPO_Name__c":"Urinary bladder sphincter dysfunction","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:100985","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003487","HPO_Synonym__c":"Extensor plantar reflexes; Extensor plantar response; Extensor plantar responses; Positive Babinski sign","HPO_Name__c":"Babinski sign","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:100985","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0004302","HPO_Synonym__c":"Functional motor problems","HPO_Name__c":"Functional motor deficit","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:100985","HPO_Frequency__c":"Uncommon (<1-4%)","Feature__r":{"HPO_Description__c":"Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001251","HPO_Synonym__c":"Cerebellar ataxia","HPO_Name__c":"Ataxia","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:100985","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001260","HPO_Synonym__c":"Difficulty articulating speech; Dysarthric speech","HPO_Name__c":"Dysarthria","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:100985","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Tendon reflexes that are noticeably more active than usual (conventionally denoted 3+ on clinical examination). Brisk reflexes may or may not indicate a neurological lesion. They are distinguished from hyperreflexia by the fact that hyerreflexia is characterized by hyperactive repeating (clonic) reflexes, which are considered to be always abnormal.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001348","HPO_Synonym__c":"Brisk deep tendon reflexes","HPO_Name__c":"Brisk reflexes","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:100985","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001257","HPO_Synonym__c":"Involuntary muscle stiffness, contraction, or spasm; Muscle spasticity; Muscular spasticity","HPO_Name__c":"Spasticity","Feature_System__c":"Nervous System; Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:100985","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Clonus is an involuntary tendon reflex that causes repeated flexion and extension of the foot. Ankle clonus is tested by rapidly flexing the foot upward.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0011448","HPO_Synonym__c":"Abnormal rhythmic movements of ankle","HPO_Name__c":"Ankle clonus","Feature_System__c":"Nervous System; Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:100985","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0008969","HPO_Name__c":"Leg muscle stiffness","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:100985","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0100543","HPO_Synonym__c":"Abnormality of cognition; Cognitive abnormality; Cognitive defects; Cognitive deficits; Cognitive impairment; Intellectual impairment","HPO_Name__c":"Cognitive impairment","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:100985","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Muscular atrophy affecting muscles in the distal portions of the extremities.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003693","HPO_Synonym__c":"Amyotrophy of distal limb muscles; Distal amyotrophy, especially of the hands and feet; Distal limb muscle atrophy; Distal muscle atrophy; Distal muscle atrophy, upper and lower limbs; Distal muscle degeneration; Distal muscle wasting; Distal muscular atrophy; Muscle atrophy, distal","HPO_Name__c":"Distal amyotrophy","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:100985","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Urge incontinence is the strong, sudden need to urinate.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000012","HPO_Synonym__c":"Overactive bladder; Urgent micturition; Urinary urgency","HPO_Name__c":"Urinary urgency","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:100985","HPO_Frequency__c":"Uncommon (<1-4%)","Feature__r":{"HPO_Description__c":"A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001250","HPO_Synonym__c":"Epileptic seizure; Seizures","HPO_Name__c":"Seizure","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:100985","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Increased intensity of the a reflex in the arm.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0007350","HPO_Synonym__c":"Hyperreflexia in upper limbs","HPO_Name__c":"Upper limb hyperreflexia","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}}],"tags":{"Cause":["Genetics"],"Disease Category":["Genetics","Neurology"],"Specialist":["Genetics","Neurology","Neuromuscular medicine","Pediatrics"],"Account":["Hereditary Spastic Paraplegia"]},"synonyms":["autosomal dominant spastic paraplegia 4"," autosomal dominant spastic paraplegia type 4"," familial spastic paraplegia autosomal dominant 2"," hereditary spastic paraplegia caused by mutation in spast"," hereditary spastic paraplegia type 4"," spast hereditary spastic paraplegia"," spastic paraplegia 4"," spastic paraplegia 4, autosomal dominant"," spg4"]}