{
  "id": 23892,
  "label": "RYR1-related myopathy",
  "model": {
    "label": "Mondo Disease Ontology (MONDO)",
    "source": 0
  },
  "type_id": 0,
  "reference_id": "MONDO:0100150",
  "properties": {
    "xrefs": [
      "GARD:0026064",
      "Orphanet:98742"
    ],
    "synonyms": [
      "RYR1-related disease",
      "RYR1-related disorder",
      "RYR1-related myopathy",
      "neurological muscular channelopathy due to a genetic ryanodine receptor defect"
    ],
    "categories": [
      {
        "ref": "MONDO:0002081",
        "name": "musculoskeletal system disorder"
      },
      {
        "ref": "MONDO:0005071",
        "name": "nervous system disorder"
      }
    ],
    "definition": "A disorder of the musculoskeletal system caused by pathogenic variants in the RYR1 gene, which encodes the ryanodine receptor type 1 protein. These variants are associated with a variety of overlapping features characterized by symmetric proximal muscle weakness, often with pronounced facial weakness with or without dysmorphism and ophthalmoparesis/ophthalmoplegia with ptosis, bulbar weakness, significant respiratory involvement, severe neonatal hypotonia, scoliosis, orthopedic deformities including arthrogryposis, hip dislocation, club feet, and King Denborough syndrome (pectus carinatum or excavatum, short stature, joint contractures, facial and skeletal deformities), malignant hyperthermia susceptibility, anesthesia-induced rhabdomyolysis, fatigue, exercise-induced hyperthermia/exertional heat stroke, and exertional myalgia. Histologic findings on skeletal muscle biopsy reveal a wide range of structural abnormalities and can include central core disease, multiminicore disease, cone-rod myopathy, centronuclear myopathy, and congenital fiber-type disproportion."
  },
  "isLeaf": false,
  "isRoot": false,
  "child_count": 5,
  "parents": [
    {
      "id": 4427,
      "label": "congenital nervous system disorder",
      "isLeaf": false,
      "isRoot": false,
      "parents": [
        6799
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "DOID:2490",
          "ICD9:742",
          "MEDGEN:105425",
          "NCIT:C97172",
          "UMLS:C0497552"
        ],
        "synonyms": [
          "congenital abnormality of the nervous system",
          "congenital nervous system disorder"
        ],
        "categories": [
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ],
        "definition": "An abnormality of the nervous system that is present at birth or detected in the neonatal period."
      },
      "child_count": 217,
      "reference_id": "MONDO:0002320"
    },
    {
      "id": 19001,
      "label": "muscular channelopathy",
      "isLeaf": false,
      "isRoot": false,
      "parents": [
        18957,
        29384
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "GARD:0018917",
          "MEDGEN:1842600",
          "Orphanet:71864",
          "UMLS:C5681306"
        ],
        "synonyms": [
          "channelopathy of muscle tissue",
          "muscle tissue channelopathy"
        ],
        "categories": [
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ],
        "definition": "A channelopathy that involves the muscle tissue."
      },
      "child_count": 24,
      "reference_id": "MONDO:0019119"
    },
    {
      "id": 19669,
      "label": "congenital myopathy",
      "isLeaf": false,
      "isRoot": false,
      "parents": [
        7023,
        24618
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "DOID:0080100",
          "DOID:0081337",
          "GARD:0005898",
          "MEDGEN:124381",
          "MedDRA:10062547",
          "NANDO:1200477",
          "NANDO:2100234",
          "OMIMPS:117000",
          "Orphanet:97245",
          "UMLS:C0270960",
          "icd11.foundation:1185572073"
        ],
        "synonyms": [
          "congenital myopathy",
          "Batten Turner congenital myopathy",
          "myopathy congenital"
        ],
        "categories": [
          {
            "ref": "MONDO:0002081",
            "name": "musculoskeletal system disorder"
          }
        ]
      },
      "child_count": 106,
      "reference_id": "MONDO:0019952"
    },
    {
      "id": 24271,
      "label": "hereditary neuromuscular disease",
      "isLeaf": false,
      "isRoot": false,
      "parents": [
        18957,
        24270
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "GARD:0026275"
        ],
        "categories": [
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ],
        "definition": "A heterogeneous group of genetic conditions with Mendelian (autosomal dominant, recessive, or X-linked) or chromosomal etiology that is characterized by progressive muscle degeneration and weakness."
      },
      "child_count": 44,
      "reference_id": "MONDO:0100546"
    }
  ],
  "children": [
    {
      "id": 8694,
      "label": "central core myopathy",
      "isLeaf": true,
      "isRoot": false,
      "parents": [
        18865,
        23892,
        23937
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "DOID:3529",
          "EFO:1000855",
          "GARD:0006014",
          "MEDGEN:1841337",
          "MESH:D020512",
          "NANDO:1200479",
          "NANDO:2200870",
          "NCIT:C83010",
          "OMIM:117000",
          "Orphanet:597",
          "SCTID:43152001",
          "UMLS:C5830701",
          "icd11.foundation:2065822840"
        ],
        "synonyms": [
          "central core disease",
          "CCD",
          "Cco",
          "Shy-Magee syndrome",
          "central CORE disease of muscle",
          "minicore myopathy, moderate, with hand involvement",
          "multicore myopathy, moderate, with hand involvement",
          "multiminicore disease, moderate, with hand involvement",
          "muscle core disease",
          "muscular central core disease",
          "myopathy, central core",
          "myopathy, central fibrillar",
          "neuromuscular disease, congenital, with uniform type 1 Fiber",
          "neuromuscular disease, congenital, with uniform type 1 Fibre"
        ],
        "categories": [
          {
            "ref": "MONDO:0002081",
            "name": "musculoskeletal system disorder"
          },
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ],
        "definition": "An autosomal dominant congenital disorder affecting the skeletal muscles. Microscopically, it is characterized by disorganized areas, which are called cores, seen usually in the center of the muscle fibers. Clinically it presents as mild to severe muscle weakness. It may be associated with skeletal abnormalities including scoliosis, joint deformities, and hip dislocation."
      },
      "child_count": 0,
      "reference_id": "MONDO:0007294"
    },
    {
      "id": 10925,
      "label": "congenital multicore myopathy with external ophthalmoplegia",
      "isLeaf": true,
      "isRoot": false,
      "parents": [
        18870,
        23892
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "GARD:0010316",
          "MEDGEN:340597",
          "NANDO:2200872",
          "NCIT:C150608",
          "OMIM:255320",
          "Orphanet:98905",
          "UMLS:C1850674"
        ],
        "synonyms": [
          "minicore myopathy, antenatal onset, with arthrogryposis",
          "minicore myopathy",
          "minicore myopathy with external ophthalmoplegia",
          "multicore myopathy",
          "multicore myopathy with external ophthalmoplegia",
          "multiminicore disease with external ophthalmoplegia",
          "multiminicore myopathy multicore myopathy with external ophthalmoplegia"
        ],
        "categories": [
          {
            "ref": "MONDO:0002081",
            "name": "musculoskeletal system disorder"
          },
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ],
        "definition": "An autosomal recessive condition caused by mutation(s) in the RYR1 gene, encoding ryanodine receptor 1. It may be characterized clinically by neonatal hypotonia, delayed motor development, and generalized muscle weakness, and amyotrophy. Pathologically, the absence of mitochondria and focal disorganization of the sarcomere appear as \"minicores\" on ATPase staining as a result of focal defects in oxidative activity."
      },
      "child_count": 0,
      "reference_id": "MONDO:0009712"
    },
    {
      "id": 18550,
      "label": "congenital myopathy with myasthenic-like onset",
      "isLeaf": true,
      "isRoot": false,
      "parents": [
        23892
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "GARD:0021783",
          "MEDGEN:1642781",
          "Orphanet:424107",
          "SCTID:763315005",
          "UMLS:C4706390"
        ],
        "synonyms": [
          "congenital myopathy with myasthenic-like onset"
        ],
        "categories": [
          {
            "ref": "MONDO:0002081",
            "name": "musculoskeletal system disorder"
          },
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ],
        "definition": "Congenital myopathy with myasthenic-like onset is a rare, genetic, non-dystrophic myopathy characterized by fatigable muscle weakness associated with congenital myopathy. Patients present with axial hypotonia, myopathic facies with fatigable ptosis, feeding difficulties, delayed gross motor development and proximal limb weakness with a RYR1-related typical pattern of muscle involvement (i.e. severe involvement of the soleus muscle and sparring of the rectus femoris, sartorius, gracilis and semitendinous muscles). Scoliosis and frequent respiratory tract infections are additional observed features."
      },
      "child_count": 0,
      "reference_id": "MONDO:0018528"
    },
    {
      "id": 19941,
      "label": "King-Denborough syndrome",
      "isLeaf": true,
      "isRoot": false,
      "parents": [
        16088,
        23892
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "GARD:0008433",
          "MEDGEN:327082",
          "MESH:C536883",
          "MESH:C537504",
          "OMIM:619542",
          "Orphanet:99741",
          "SCTID:764957003",
          "UMLS:C1840365"
        ],
        "synonyms": [
          "Koussef-Nichols syndrome",
          "King Denborough syndrome",
          "Kousseff Nichols syndrome",
          "Noonan like contracture myopathy hyperpyrexia",
          "anesthetic-induced malignant hyperpyrexia in children"
        ],
        "categories": [
          {
            "ref": "MONDO:0002081",
            "name": "musculoskeletal system disorder"
          },
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ],
        "definition": "A rare genetic non-dystrophic myopathy characterized by the triad of congenital myopathy, dysmorphic features and susceptibility to malignant hyperthermia. Patients present with a wide phenotypic range, including delayed motor development, muscle weakness and fatigability, ptosis and facies myopathica (with or without creatine kinase elevations), skeletal abnormalities (e.g. short stature, scoliosis, kyphosis, lumbar lordosis and pectus carinatum/excavatum), mild dysmorphic facial features (e.g. hypertelorism, down-slanting palpebral fissures, epicanthic folds, low set ears, micrognathia), webbing of the neck, cryptorchidism, and a susceptibility to malignant hyperthermia and/or rhabdomyolysis due to intensive physical strain, viral infection or statin use."
      },
      "child_count": 0,
      "reference_id": "MONDO:0020485"
    },
    {
      "id": 25216,
      "label": "rhabdomyolysis-myalgia syndrome",
      "isLeaf": true,
      "isRoot": false,
      "parents": [
        23892
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "DOID:0080992",
          "GARD:0026612"
        ],
        "categories": [
          {
            "ref": "MONDO:0002081",
            "name": "musculoskeletal system disorder"
          },
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ],
        "definition": "A myopathy that is characterized by muscle breakdown (rhabdomyolysis), heat and exertion-related muscle pain (myalgia) and cramping symptoms, severe muscle pain, sudden elevation and subsequent fall of serum creatine phosphokinase levels and products of muscle breakdown in the urine (myoglobinuria). Associated with RYR1 variations. Rhabdomyolysis is associated with a range of external triggers, including strenuous exercise beyond the limit of fatigue, heat stress, illicit drug or alcohol abuse, use of supplements or certain medications, recent viral illness or muscle trauma."
      },
      "child_count": 0,
      "reference_id": "MONDO:0850415"
    }
  ],
  "roots": [
    {
      "id": 4427,
      "label": "congenital nervous system disorder"
    },
    {
      "id": 19001,
      "label": "muscular channelopathy"
    },
    {
      "id": 19669,
      "label": "congenital myopathy"
    },
    {
      "id": 24271,
      "label": "hereditary neuromuscular disease"
    }
  ]
}