{"Name":"Hypomyelinating leukodystrophy 12","DiseaseID__c":"GARD:0017837","id":17837,"encodedName":"hypomyelinating-leukodystrophy-12","IsDeleted":false,"Disease_Name_Full__c":"Hypomyelinating leukodystrophy 12","Xref_IDs__c":"C4225247; DOID:0060796; MEDGEN:905068; MONDO:0014732; OMIM:616683; ORPHA:466934","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":4,"Disease_Characteristics_Score__c":8,"No_of_Age_at_Onset__c":1,"Description_Source__c":"MONDO:0014732","Disease_Description__c":"Any leukodystrophy in which the cause of the disease is a mutation in the VPS11 gene.","GARD_Name__c":"Hypomyelinating leukodystrophy 12","GARD_Synonym__c":"hld12; hypomyelinating leukodystrophy type 12; leukodystrophy caused by mutation in vps11; leukodystrophy, hypomyelinating, 12; leukodystrophy, hypomyelinating, type 12; vps11 leukodystrophy; vps11-related autosomal recessive hypomyelinating leukodystrophy; vps11-related autosomal recessive hypomyelinating leukoencephalopathy","Curated_Disease_Description_Source__c":"ORPHA:466934","Curated_Disease_Description__c":"A rare genetic leukodystrophy identified in families of Ashkenazi Jewish descent, characterized by infancy onset of severe global developmental delay with very limited or absent speech and sometimes complete absence of motor development, hypotonia, spasticity, and acquired microcephaly. Seizures, hearing loss, visual impairment, and autonomic dysfunction have also been described. Brain imaging shows delayed myelination and other white matter abnormalities.","Curated_USA_Estimate_Source__c":null,"Curated_USA_Estimate__c":"1,000","Age_at_Onset_Snippet_Text__c":"as an Infant","SourceID__c":"ORPHA:466934","Deprecated__c":"No","Disease_Concept_Type__c":"Rare Disease Entity","MONDO_ID__c":"MONDO:0014732","ORPHANET_ID__c":"ORPHA:466934","Replaced_By_ID__c":null,"Display_Spanish_Disease_Name__c":"Leucodistrofia hipomielinizante autosómica recesiva asociada a vps11","Spanish_Description_Source__c":null,"Spanish_Description__c":null,"Spanish_Disease_Name__c":"leucodistrofia hipomielinizante autosómica recesiva asociada a vps11","Spanish_GARD_Synonym__c":"leucoencefalopatía hipomielinizante autosómica recesiva asociada a vps11","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":"A rare genetic leukodystrophy identified in families of Ashkenazi Jewish descent, characterized by infancy onset of severe global developmental delay with very limited or absent speech and sometimes complete absence of motor development, hypotonia, spasticity, and acquired microcephaly. Seizures, hearing loss, visual impairment, and autonomic dysfunction have also been described. Brain imaging shows delayed myelination and other white matter abnormalities.","Curated_Disease_Description_Source__c":"ORPHA:466934","GARD_Synonym__c":"hld12; hypomyelinating leukodystrophy type 12; leukodystrophy caused by mutation in vps11; leukodystrophy, hypomyelinating, 12; leukodystrophy, hypomyelinating, type 12; vps11 leukodystrophy; vps11-related autosomal recessive hypomyelinating leukodystrophy; vps11-related autosomal recessive hypomyelinating leukoencephalopathy","Name":"Hypomyelinating leukodystrophy 12","Curated_USA_Estimate__c":"1,000","estimateUsa":"1,000"}],"Organization_Supported_Diseases__c":[{"Account_Name__c":"United Leukodystrophy Foundation","Website__c":"https://ulf.org/"},{"Account_Name__c":"Alex The Leukodystrophy Charity","Website__c":"https://www.alextlc.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":"Leukodystrophy","Tag_Category__c":"Account;Cause;Disease Category","category_description":"Leukodystrophies are a group of genetic neurological diseases that affect the white matter of the brain and spinal cord.","curated_tag_name":"Leukodystrophies"},{"Tag_Name__c":"Neurodevelopmental disabilities","Tag_Category__c":"Specialist","curated_tag_name":"Neurodevelopmental disabilities"},{"Tag_Name__c":"Pediatrics","Tag_Category__c":"Specialist"}],"Age_At_Onset__c":[{"Age_At_Onset__c":"Infancy","Provided_By__c":"ORPHA:466934"}],"External_Identifier_Disease__c":[{"URL__c":"https://uts.nlm.nih.gov/uts/umls/concept/C4225247","Source__c":"C4225247","Xref__c":"C4225247"},{"URL__c":"https://www.ebi.ac.uk/ols4/ontologies/doid/classes?obo_id=DOID%3A0060796","Source__c":"MONDO:0014732","Xref__c":"DOID:0060796"},{"URL__c":"https://www.orpha.net/en/disease/detail/466934","Source__c":"C4225247; MONDO:0014732","Xref__c":"ORPHA:466934"},{"URL__c":"https://www.ncbi.nlm.nih.gov/medgen/?term=905068","Source__c":"C4225247","Xref__c":"MEDGEN:905068"},{"URL__c":"https://www.omim.org/entry/616683","Source__c":"C4225247; MONDO:0014732; ORPHA:466934","Xref__c":"OMIM:616683"},{"URL__c":"http://purl.obolibrary.org/obo/MONDO_0014732","Source__c":"GARD:0017837","Xref__c":"MONDO:0014732"}],"GARD_Disease_Gene__c":[{"GeneSymbol__c":"VPS11","Gene_Type__c":"protein-coding gene","Causal_Gene__c":true}],"Inheritance__c":["Autosomal recessive"],"GARD_Disease_Feature__c":[{"Provided_By__c":"ORPHA:466934","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Underdevelopment of the corpus callosum.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002079","HPO_Synonym__c":"Corpus callosum hypoplasia; Hypoplasia of corpus callosum; Hypoplastic corpus callosum; Underdevelopment of part of brain called corpus callosum","HPO_Name__c":"Hypoplasia of the corpus callosum","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:466934","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"A form of loss of vision caused by damage to the visual cortex rather than a defect in the eye.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0100704","HPO_Synonym__c":"Cortical blindness; Cortical visual impairment; Cortical/cerebral visual impairment; CVI","HPO_Name__c":"Cerebral visual impairment","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:466934","HPO_Frequency__c":"Very frequent (80-99%)","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:466934","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A functional abnormality of the autonomic nervous system.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0012332","HPO_Synonym__c":"Autonomic dysfunction; Autonomic dysregulation; Dysautonomia","HPO_Name__c":"Abnormal autonomic nervous system physiology","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:466934","HPO_Frequency__c":"Excluded (0%)","Feature__r":{"HPO_Description__c":"Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000280","HPO_Synonym__c":"Coarse face; Coarse facial appearance; Coarse facial features; Coarse facies","HPO_Name__c":"Coarse facial features","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:466934","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Complete lack of development of speech and language abilities.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001344","HPO_Synonym__c":"Absent speech development; Lack of language development; Lack of speech; No speech development; No speech or language development; Nonverbal","HPO_Name__c":"Absent speech","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:466934","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000648","HPO_Synonym__c":"Optic nerve atrophy; Optic-nerve degeneration","HPO_Name__c":"Optic atrophy","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:466934","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Infrequent or difficult evacuation of feces.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002019","HPO_Synonym__c":"Constipation; Costiveness; Dyschezia","HPO_Name__c":"Constipation","Feature_System__c":"Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:466934","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Oral-motor apraxia is the inability to volitionally sequence oral movements of the speech structure for nonspeech tasks in the absence of neuromuscular deficits such as paralysis or muscle weakness. Oral-motor apraxia is diagnosed when, despite intact sensory motor function an individual is unable to use these effector systems under voluntary control.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0007301","HPO_Synonym__c":"Oral-motor apraxia","HPO_Name__c":"Oromotor apraxia","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:466934","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001252","HPO_Synonym__c":"Low muscle tone; Low or weak muscle tone; Muscle hypotonia; Muscular hypotonia","HPO_Name__c":"Hypotonia","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:466934","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0007204","HPO_Name__c":"Diffuse white matter abnormalities","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:466934","HPO_Frequency__c":"Excluded (0%)","Feature__r":{"HPO_Description__c":"Simultaneous enlargement of the liver and spleen.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001433","HPO_Synonym__c":"Enlarged liver and spleen","HPO_Name__c":"Hepatosplenomegaly","Feature_System__c":"Cardiovascular System; Immune System; Digestive System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:466934","HPO_Frequency__c":"Very frequent (80-99%)","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:466934","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"Head circumference below 2 standard deviations below the mean for age and sex.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000252","HPO_Synonym__c":"Abnormally small cranium; Abnormally small skull; Decreased circumference of cranium; Decreased size of cranium; Decreased size of skull; Reduced head circumference; small cranium; Small head circumference","HPO_Name__c":"Microcephaly","Feature_System__c":"Nervous System; Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:466934","HPO_Frequency__c":"Very frequent (80-99%)","Feature__r":{"HPO_Description__c":"A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001263","HPO_Synonym__c":"Delayed cognitive development; Delayed development; Delayed developmental milestones; Delayed intellectual development; Delayed milestones; Delayed psychomotor development; Developmental delay; Developmental delay in early childhood; Developmental delay, global; Developmental retardation; GDD; Lack of psychomotor development; Motor and developmental delay; Motormental retardation; Psychomotor delay; Psychomotor development deficiency; Psychomotor development failure; Psychomotor developmental delay; Retarded development; Retarded mental development; Retarded psychomotor development","HPO_Name__c":"Global developmental delay","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:466934","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A deficiency or slowing down of growth pre- and postnatally.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001510","HPO_Synonym__c":"Delayed growth; Growth deficiency; Growth delay; Growth failure; Growth retardation; Poor growth; Retarded growth","HPO_Name__c":"Growth delay","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:466934","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A febrile seizure is any type of seizure (most often a generalized tonic-clonic seizure) occurring with fever (at least 38 degrees Celsius) but in the absence of central nervous system infection, severe metabolic disturbance or other alternative precipitant in children between the ages of 3 months and 6 years.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002373","HPO_Synonym__c":"Febrile convulsion; Febrile seizures; Fever induced seizures; Seizures, febrile, in early childhood; Seizures, generalized, associated with fever","HPO_Name__c":"Febrile seizure (within the age range of 3 months to 6 years)","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:466934","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A type of bladder dysfunction caused by neurologic damage. Neurogenic bladder can be flaccid or spastic. Common manifestatios of neurogenic bladder are overflow incontinence, frequency, urgency, urge incontinence, and retention.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000011","HPO_Synonym__c":"Lack of bladder control due to nervous system injury","HPO_Name__c":"Neurogenic bladder","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:466934","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:466934","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0000407","HPO_Synonym__c":"Hearing loss, sensorineural; Sensorineural deafness; Sensorineural hearing loss","HPO_Name__c":"Sensorineural hearing impairment","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:466934","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"Delayed myelination in the central nervous system.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002188","HPO_Synonym__c":"Delay in central nervous system myelination","HPO_Name__c":"Delayed CNS myelination","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:466934","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002465","HPO_Synonym__c":"Poor speech","HPO_Name__c":"Poor speech","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:466934","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"An increase in size of the ventricular system of the brain.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002119","HPO_Synonym__c":"Cerebral ventricular dilatation; Dilated cerebral ventricle; Dilated cerebral ventricles; Dilated ventricles; Enlarged cerebral ventricles; Enlarged ventricles; Enlarged ventricular system; Large cerebral ventricles and cisternae; Ventricular dilatation","HPO_Name__c":"Ventriculomegaly","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:466934","HPO_Frequency__c":"Uncommon (<1-4%)","Feature__r":{"HPO_Description__c":"Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0001272","HPO_Synonym__c":"Atrophic cerebellum; Degeneration of cerebellum","HPO_Name__c":"Cerebellar atrophy","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:466934","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Description__c":"A structural abnormality of the myelinated axons (white matter) located near the cerebral ventricles.","HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002518","HPO_Synonym__c":"Abnormality of the periventricular white matter","HPO_Name__c":"Abnormal periventricular white matter morphology","Feature_System__c":"Nervous System","HPO_Feature_Type__c":"Symptom"}},{"Provided_By__c":"ORPHA:466934","HPO_Frequency__c":"Frequent (30-79%)","Feature__r":{"HPO_Feature_URL__c":"https://hpo.jax.org/browse/term/HP:0002828","HPO_Name__c":"Multiple joint contractures","Feature_System__c":"Musculoskeletal System","HPO_Feature_Type__c":"Symptom"}}],"tags":{"Cause":["Genetics","Leukodystrophy"],"Disease Category":["Genetics","Neurology","Leukodystrophy"],"Specialist":["Genetics","Neurology","Neurodevelopmental disabilities","Pediatrics"],"Account":["Leukodystrophy"]},"synonyms":["hld12"," hypomyelinating leukodystrophy type 12"," leukodystrophy caused by mutation in vps11"," leukodystrophy, hypomyelinating, 12"," leukodystrophy, hypomyelinating, type 12"," vps11 leukodystrophy"," vps11-related autosomal recessive hypomyelinating leukodystrophy"," vps11-related autosomal recessive hypomyelinating leukoencephalopathy"]}