{"Name":"Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures","DiseaseID__c":"GARD:0013222","id":13222,"encodedName":"autosomal-dominant-childhood-onset-proximal-spinal-muscular-atrophy-with-contractures","IsDeleted":false,"Disease_Name_Full__c":"Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures","Xref_IDs__c":"C191766; C4747715; DOID:0070349; MEDGEN:1669929; MONDO:0014121; OMIM:615290; ORPHA:363454","USA_Estimate__c":"1,000","No_of_Specialist_Tagsa__c":4,"No_of_ClinGen_records__c":0,"No_of_GeneReviews__c":0,"No_of_HHS_records__c":0,"World_Estimate__c":"1 to 8,000","No_of_HRSA_records__c":0,"Evidence_Based_Score__c":0,"No_of_Disease_Descriptions__c":2,"Disease_Characteristics_Score__c":7,"No_of_Age_at_Onset__c":4,"Description_Source__c":"GARD:0013222","Disease_Description__c":"Autosomal dominant spinal muscular atrophy, lower extremity-predominant 2 (SMALED2) is a rare neurological disease characterized by early-childhood onset of muscle weakness and loss of muscle tissue (muscle atrophy), mostly affecting the muscles of the thighs. It is a subtype of the group of diseases known as spinal muscular atrophy. Symptoms include delayed walking, waddling gait, difficulty walking, foot deformities, and loss of some reflexes. Joint contractures are reported frequently, and a few patients present with congenital hip dysplasia. Other symptoms that have being described are an exaggerated curvature of the lower back (hyperlordosis), increased or decreased muscle tone, small chin (micrognathia), respiratory insufficiency, small head (microcephaly), and extra ridges or folds in the brain surface (polymicrogyria). Sensation and cognitive function are normal in most cases. Many patients show evident atrophy of the lower limbs and a very broad upper body, which resembles a bodybuilder-like shape. It is caused by genetic changes in the BICD2 gene. Inheritance is autosomal dominant.","GARD_Name__c":"Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures","GARD_Synonym__c":"bicd2-related autosomal dominant childhood-onset proximal spinal muscular atrophy; bicd2-related lower extremity-predominant autosomal dominant proximal spinal muscular atrophy with contractures; lower extremity-predominant autosomal dominant proximal spinal muscular atrophy with contractures; smaled2; smaled2a; spinal muscular atrophy, lower extremity-predominant, 2a, autosomal dominant; spinal muscular atrophy, lower extremity-predominant, 2a, childhood onset, autosomal dominant","Curated_Disease_Description_Source__c":"GARD:0013222","Curated_Disease_Description__c":"BICD2-related autosomal dominant childhood-onset proximal spinal muscular atrophy (SMALED2) is a rare neurological disease characterized by early-childhood onset of muscle weakness and loss of muscle tissue (muscle atrophy), mostly affecting the muscles of the thighs. It is a subtype of the group of diseases known as spinal muscular atrophy. Symptoms include delayed walking, waddling gait, difficulty walking, foot deformities, and loss of some reflexes. Joint contractures are reported frequently, and a few patients present with congenital hip dysplasia. Other symptoms that have being described are an exaggerated curvature of the lower back (hyperlordosis), increased or decreased muscle tone, small chin (micrognathia), respiratory insufficiency, small head (microcephaly), and extra ridges or folds in the brain surface (polymicrogyria). Sensation and cognitive function are normal in most cases. Many patients show evident atrophy of the lower limbs and a very broad upper body, which resembles a bodybuilder-like shape. It is caused by genetic changes in the BICD2 gene. Inheritance is autosomal dominant.","Curated_USA_Estimate_Source__c":null,"Curated_USA_Estimate__c":"1,000","Age_at_Onset_Snippet_Text__c":"at a variety of ages","SourceID__c":"ORPHA:363454","Deprecated__c":"No","Disease_Concept_Type__c":"Rare Disease Entity","MONDO_ID__c":"MONDO:0014121","ORPHANET_ID__c":"ORPHA:363454","Replaced_By_ID__c":null,"Display_Spanish_Disease_Name__c":"Atrofia muscular espinal proximal asociada a bicd2 autosómica dominante de inicio en la infancia","Spanish_Description_Source__c":null,"Spanish_Description__c":null,"Spanish_Disease_Name__c":"atrofia muscular espinal proximal asociada a bicd2 autosómica dominante de inicio en la infancia","Spanish_GARD_Synonym__c":"atrofia muscular espinal proximal asociada a bicd2 con predominio en extremidades inferiores autosómica dominante con contracturas; smaled2","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":"BICD2-related autosomal dominant childhood-onset proximal spinal muscular atrophy (SMALED2) is a rare neurological disease characterized by early-childhood onset of muscle weakness and loss of muscle tissue (muscle atrophy), mostly affecting the muscles of the thighs. It is a subtype of the group of diseases known as spinal muscular atrophy. Symptoms include delayed walking, waddling gait, difficulty walking, foot deformities, and loss of some reflexes. Joint contractures are reported frequently, and a few patients present with congenital hip dysplasia. Other symptoms that have being described are an exaggerated curvature of the lower back (hyperlordosis), increased or decreased muscle tone, small chin (micrognathia), respiratory insufficiency, small head (microcephaly), and extra ridges or folds in the brain surface (polymicrogyria). Sensation and cognitive function are normal in most cases. Many patients show evident atrophy of the lower limbs and a very broad upper body, which resembles a bodybuilder-like shape. It is caused by genetic changes in the BICD2 gene. Inheritance is autosomal dominant.","Curated_Disease_Description_Source__c":"GARD:0013222","GARD_Synonym__c":"bicd2-related autosomal dominant childhood-onset proximal spinal muscular atrophy; bicd2-related lower extremity-predominant autosomal dominant proximal spinal muscular atrophy with contractures; lower extremity-predominant autosomal dominant proximal spinal muscular atrophy with contractures; smaled2; smaled2a; spinal muscular atrophy, lower extremity-predominant, 2a, autosomal dominant; spinal muscular atrophy, lower extremity-predominant, 2a, childhood onset, autosomal dominant","Name":"Autosomal dominant childhood-onset proximal spinal muscular atrophy with contrac","Curated_USA_Estimate__c":"1,000","estimateUsa":"1,000"}],"Organization_Supported_Diseases__c":[{"Account_Name__c":"Cure SMA","Website__c":"https://www.curesma.org/"},{"Account_Name__c":"Cure SMA Canada","Website__c":"https://curesma.ca/"},{"Account_Name__c":"Muscular Dystrophy Canada","Website__c":"https://muscle.ca/"}],"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":"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":"Neonatal","Provided_By__c":"ORPHA:363454"},{"Age_At_Onset__c":"Infancy","Provided_By__c":"ORPHA:363454"},{"Age_At_Onset__c":"Antenatal","Provided_By__c":"ORPHA:363454"},{"Age_At_Onset__c":"Childhood","Provided_By__c":"ORPHA:363454"}],"External_Identifier_Disease__c":[{"URL__c":"https://raresource.nih.gov/diseases/filter/0013222","Source__c":"RareSource"},{"URL__c":"https://www.omim.org/entry/615290","Source__c":"C4747715; MONDO:0014121","Xref__c":"OMIM:615290"},{"URL__c":"https://www.ncbi.nlm.nih.gov/medgen/?term=1669929","Source__c":"C4747715","Xref__c":"MEDGEN:1669929"},{"URL__c":"https://www.ebi.ac.uk/ols4/ontologies/doid/classes?obo_id=DOID%3A0070349","Source__c":"MONDO:0014121","Xref__c":"DOID:0070349"},{"URL__c":"https://www.orpha.net/en/disease/detail/363454","Source__c":"C4747715; MONDO:0014121; ORPHA:363454","Xref__c":"ORPHA:363454"},{"URL__c":"https://uts.nlm.nih.gov/uts/umls/concept/C4747715","Source__c":"C4747715","Xref__c":"C4747715"},{"URL__c":"http://purl.obolibrary.org/obo/MONDO_0014121","Source__c":"GARD:0013222","Xref__c":"MONDO:0014121"},{"URL__c":"https://evsexplore.semantics.cancer.gov/evsexplore/concept/ncit/C191766","Source__c":"C4747715","Xref__c":"C191766"}],"GARD_Disease_Gene__c":[{"GeneSymbol__c":"BICD2","GHR_URL__c":"https://medlineplus.gov/genetics/gene/bicd2","Gene_Type__c":"protein-coding gene","Causal_Gene__c":true}],"Inheritance__c":["Autosomal dominant"],"GARD_Disease_Feature__c":[{"Provided_By__c":"ORPHA:363454","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A lack of strength of the proximal muscles.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003701","HPO_Synonym__c":"Muscle weakness, proximal; Proximal limb muscle weakness; Proximal limb weakness; Weakness in muscles of upper arms and upper legs","HPO_Name__c":"Proximal muscle weakness","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:363454","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001371","HPO_Synonym__c":"Flexed joint that cannot be straightened; Flexion contractures; Flexion contractures of joints","HPO_Name__c":"Flexion contracture","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:363454","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Weakness of the hip girdle and upper thigh muscles, for instance in myopathies, leads to an instability of the pelvis on standing and walking. If the muscles extending the hip joint are affected, the posture in that joint becomes flexed and lumbar lordosis increases. The patients usually have difficulties standing up from a sitting position. Due to weakness in the gluteus medius muscle, the hip on the side of the swinging leg drops with each step (referred to as Trendelenburg sign). The gait appears waddling. The patients frequently attempt to counteract the dropping of the hip on the swinging side by bending the trunk towards the side which is in the stance phase (in the German language literature this is referred to as Duchenne sign). Similar gait patterns can be caused by orthopedic conditions when the origin and the insertion site of the gluteus medius muscle are closer to each other than normal, for instance due to a posttraumatic elevation of the trochanter or pseudarthrosis of the femoral neck.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002515","HPO_Synonym__c":"Waddling gait; Waddling walk","HPO_Name__c":"Waddling gait","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:363454","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0005853","HPO_Name__c":"Congenital foot contraction deformities","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:363454","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001347","HPO_Synonym__c":"Increased deep tendon reflexes; Increased reflexes","HPO_Name__c":"Hyperreflexia","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:363454","HPO_Frequency__c":"Uncommon (<1-4%)","Feature__r":{"HPO_Description__c":"The shoulder, or pectoral, girdle is composed of the clavicles and the scapulae. Shoulder-girdle weakness refers to lack of strength of the muscles attaching to these bones, that is, lack of strength of the muscles around the shoulders.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003547","HPO_Synonym__c":"Muscle weakness, shoulder-girdle; Shoulder girdle weakness; Shoulder weakness; Weak shoulder muscles","HPO_Name__c":"Shoulder girdle muscle weakness","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:363454","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"An abnormality of the Achilles tendon.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0005109","HPO_Synonym__c":"Abnormality of the Achilles tendon; Abnormality of the calcaneal tendon","HPO_Name__c":"Abnormal Achilles tendon morphology","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:363454","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"An abnormal reduction in quantity or strength of fetal movements.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001558","HPO_Synonym__c":"Decreased fetal activity; Decreased fetal movements; Decreased movement in utero; Dminished fetal movement; Fetal hypokinesia; Less than 10 fetal movements in 12 hours; Reduced fetal movement; Reduced fetal movements","HPO_Name__c":"Decreased fetal movement","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:363454","HPO_Frequency__c":"Uncommon (<1-4%)","Feature__r":{"HPO_Description__c":"Reduced strength of the musculature of the hand.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0030237","HPO_Synonym__c":"Hand muscle weakness","HPO_Name__c":"Hand muscle weakness","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:363454","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Abnormally increased curvature (anterior concavity) of the lumbar or cervical spine.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003307","HPO_Synonym__c":"Lordosis; Prominent swayback","HPO_Name__c":"Hyperlordosis","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:363454","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"The presence of developmental dysplasia of the hip.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001385","HPO_Synonym__c":"Congenital hip dysplasia; DDH; Developmental dysplasia of the hip","HPO_Name__c":"Hip dysplasia","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:363454","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Muscular atrophy of distal leg muscles.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0008944","HPO_Synonym__c":"Lower leg amyotrophy; Lower limb degeneration; Muscle atrophy, lower limb, distal","HPO_Name__c":"Distal lower limb amyotrophy","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:363454","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"A type of Developmental delay characterized by a delay in acquiring motor skills.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001270","HPO_Synonym__c":"Delay in development of motor milestones; Delay in motor development; Delayed development of motor milestones; Delayed early motor milestones; Delayed motor development; Delayed motor milestones; Locomotor delay; Motor developmental delay; Motor developmental milestones not achieved; Motor retardation; Retarded motor development; Slow development of motor milestones","HPO_Name__c":"Motor delay","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:363454","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"The term gait disturbance can refer to any disruption of the ability to walk.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001288","HPO_Synonym__c":"Abnormal gait; Abnormal walk; Difficulty in walking; Gait abnormalities; Gait difficulties; Gait disturbances; Impaired gait; Walking disability","HPO_Name__c":"Gait disturbance","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:363454","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A phenomenon whereby patients are not able to stand up without the use of the hands owing to weakness of the proximal muscles of the lower limbs.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0003391","HPO_Synonym__c":"Gower sign; Positive Gower sign; Positive Gowers sign","HPO_Name__c":"Gowers sign","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:363454","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Reduced strength of the musculature of the distal extremities.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002460","HPO_Synonym__c":"Distal limb muscle weakness; Distal limb weakness; Distal muscular weakness; Distal paresis; Muscle weakness, distal; Muscle weakness, distal limbs, due to neuronopathy; Weakness of distal muscles; Weakness of outermost muscles","HPO_Name__c":"Distal muscle weakness","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:363454","HPO_Frequency__c":"Occasional (5-29%)","Feature__r":{"HPO_Description__c":"Reduction of neurologic reflexes such as the knee-jerk reaction.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001265","HPO_Synonym__c":"Decreased reflex response; Decreased reflexes","HPO_Name__c":"Hyporeflexia","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}}],"tags":{"Cause":["Genetics"],"Disease Category":["Genetics","Neurology"],"Specialist":["Genetics","Neurology","Neuromuscular medicine","Pediatrics"]},"synonyms":["bicd2-related autosomal dominant childhood-onset proximal spinal muscular atrophy"," bicd2-related lower extremity-predominant autosomal dominant proximal spinal muscular atrophy with contractures"," lower extremity-predominant autosomal dominant proximal spinal muscular atrophy with contractures"," smaled2"," smaled2a"," spinal muscular atrophy, lower extremity-predominant, 2a, autosomal dominant"," spinal muscular atrophy, lower extremity-predominant, 2a, childhood onset, autosomal dominant"]}