{
  "id": 24020,
  "label": "overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes",
  "model": {
    "label": "Mondo Disease Ontology (MONDO)",
    "source": 0
  },
  "type_id": 0,
  "reference_id": "MONDO:0100283",
  "properties": {
    "xrefs": [
      "GARD:0026123"
    ],
    "synonyms": [
      "overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes"
    ],
    "categories": [
      {
        "ref": "MONDO:0005071",
        "name": "nervous system disorder"
      }
    ],
    "definition": "A disease caused by mosaic gain-of-function (GoF) of several genes in the MTOR pathway (MTOR, PIK3CA, PIK3R2 and AKT3) are functionally the same despite significant phenotypic variability. These GoF variants result in overgrowth due to an over-activation of key genes in this pathway. The phenotypic variability is generally attributed to the mosaic fraction and affected tissue types. For example, macrocephaly is noted if the variant is identified in the brain, but non symmetric overgrowth of that limb is noted when the variant is only present in the affected limb. The pathologies of the affected tissue often reveal similar characteristics such as cellular overgrowth. However, this is not always the case especially with focal cortical dysplasia. At times the characteristics pathologies are not present in the tissue but sampling biases are an issue. FCD resections often involve a very small area and so a very small amount of tissue is available for pathology and it is not guaranteed that lesional tissue is sent. Therefore, having a single disease term which can encompass the phenotypic variability yet provide a unifying molecular diagnosis name makes sense given the common functional mechanism."
  },
  "isLeaf": false,
  "isRoot": false,
  "child_count": 5,
  "parents": [
    {
      "id": 19709,
      "label": "central nervous system malformation",
      "isLeaf": false,
      "isRoot": false,
      "parents": [
        6799,
        19507
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "GARD:0019394",
          "ICD10CM:Q00-Q07",
          "MEDGEN:374250",
          "MESH:D009421",
          "NANDO:2200118",
          "Orphanet:98044",
          "UMLS:C1839543"
        ],
        "categories": [
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ]
      },
      "child_count": 108,
      "reference_id": "MONDO:0020022"
    }
  ],
  "children": [
    {
      "id": 12360,
      "label": "megalencephaly-capillary malformation-polymicrogyria syndrome",
      "isLeaf": true,
      "isRoot": false,
      "parents": [
        24020,
        24270,
        29234
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "GARD:0006950",
          "ICD9:759.89",
          "MEDGEN:355421",
          "MESH:C536142",
          "NANDO:2200823",
          "NORD:1423",
          "OMIM:602501",
          "Orphanet:60040",
          "SCTID:703370002",
          "UMLS:C1865285"
        ],
        "synonyms": [
          "MCAP",
          "MCM",
          "MCMTC",
          "Megalencephaly-Capillary Malformation",
          "macrocephaly-capillary malformation syndrome",
          "macrocephaly-cutis marmorata telangiectatica congenita syndrome",
          "megalencephaly-capillary malformation syndrome",
          "megalencephaly-capillary malformation-polymicrogyria syndrome",
          "megalencephaly-capillary malformation-polymicrogyria syndrome, somatic",
          "megalencephaly-cutis marmorata telangiectatica congenita syndrome",
          "M-CM",
          "M-CMTC",
          "macrocephaly cutis marmorata telangiectatica congenita",
          "macrocephaly-capillary malformation",
          "macrocephaly-cutis marmorata telangiectatica congenita",
          "megalencephaly cutis marmorata telangiectatica congenita",
          "megalencephaly-cutis marmorata telangiectatica congenita",
          "megalocephaly cutis marmorata telangiectatica congenita"
        ],
        "categories": [
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ],
        "definition": "A polymalfomative syndrome characterized by cutaneous capillary malformations, megalencephaly, cortical brain malformations (most distinctively polymicrogyria), abnormalities of somatic growth with body and brain asymmetry, developmental delay, and characteristic facial dysmorphism."
      },
      "child_count": 0,
      "reference_id": "MONDO:0011240"
    },
    {
      "id": 15709,
      "label": "macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome",
      "isLeaf": true,
      "isRoot": false,
      "parents": [
        4427,
        16087,
        24020,
        24270
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "GARD:0013636",
          "MEDGEN:899689",
          "NORD:91167",
          "OMIM:616638",
          "Orphanet:457485",
          "UMLS:C4225259"
        ],
        "synonyms": [
          "MINDS syndrome",
          "Smith-Kingsmore Syndrome",
          "Smith-Kingsmore syndrome",
          "SKS",
          "SMITH-Kingsmore syndrome",
          "macrocephaly, seizures, intellectual disability, umbilical hernia, and Facial Dysmorphism",
          "macrocephaly, seizures, mental retardation, umbilical hernia, and Facial Dysmorphism"
        ],
        "categories": [
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ],
        "definition": "A rare multiple congenital anomalies/dysmorphic syndrome with intellectual disability, characterized by macrocephaly, intellectual disability, seizures, dysmorphic facial features (including tall forehead, downslanting palpebral fissures, hypertelorism, depressed nasal bridge, and macrostomia), megalencephaly, and small thorax. Other reported features are umbilical hernia, muscular hypotonia, global developmental delay, autistic behavior, and café-au-lait spots, among others."
      },
      "child_count": 0,
      "reference_id": "MONDO:0014716"
    },
    {
      "id": 18924,
      "label": "isolated focal cortical dysplasia",
      "isLeaf": false,
      "isRoot": false,
      "parents": [
        17471,
        24020
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "GARD:0016671",
          "MEDGEN:1645432",
          "NANDO:1200564",
          "Orphanet:65683",
          "SCTID:766710005",
          "UMLS:C4707795"
        ],
        "synonyms": [
          "epilepsy due to FCD"
        ],
        "categories": [
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ],
        "definition": "Isolated focal cortical dysplasia is a rare, genetic, non-syndromic cerebral malformation due to abnormal neuronal migration disorder characterized by variable-sized, focalized malformations located in any part(s) of the cerebral cortex, which manifests with drug-resistant epilepsy (usually leading to intellectual disability) and behavioral disturbances. Abnormal MRI findings (e.g. abnormal white and/or gray matter signal, blurred gray-white matter junction, localized volume loss, cortical thickening, abnormal gyral pattern, abnormal hippocampus) and variable histopathologic patterns are associated."
      },
      "child_count": 4,
      "reference_id": "MONDO:0019009"
    },
    {
      "id": 19209,
      "label": "megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome",
      "isLeaf": false,
      "isRoot": false,
      "parents": [
        3395,
        12458,
        24020,
        24270,
        29234
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "GARD:0010341",
          "MEDGEN:355095",
          "OMIMPS:603387",
          "Orphanet:83473",
          "SCTID:722036008",
          "UMLS:C1863924"
        ],
        "synonyms": [
          "MPPH syndrome",
          "megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus",
          "megalencephaly, polymicrogyria, and hydrocephalus (MPPH) syndrome",
          "megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome"
        ],
        "categories": [
          {
            "ref": "MONDO:0002081",
            "name": "musculoskeletal system disorder"
          },
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ],
        "definition": "Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome is characterized by megalencephaly, polymicrogyria, and hydrocephalus with variable polydactyly. It has been described in six unrelated patients. Intellectual deficit or slow development is also present. The mode of inheritance of this syndrome is unknown since all cases were sporadic."
      },
      "child_count": 15,
      "reference_id": "MONDO:0019375"
    },
    {
      "id": 19946,
      "label": "hemimegalencephaly",
      "isLeaf": true,
      "isRoot": false,
      "parents": [
        24020
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "GARD:0002637",
          "ICD9:742.4",
          "MEDGEN:140910",
          "MESH:D065705",
          "NANDO:1200563",
          "NCIT:C177779",
          "NORD:1220",
          "Orphanet:99802",
          "SCTID:253170008",
          "UMLS:C0431391",
          "icd11.foundation:961229160"
        ],
        "synonyms": [
          "unilateral megalencephaly",
          "macrencephaly"
        ],
        "categories": [
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ],
        "definition": "Hemimegalencephaly is a rare cerebral malformation characterized by overgrowth of all or part of a cerebral hemisphere, often with ipsilateral severe cortical dysplasia or dysgenesis, white matter hypertrophy and dilated lateral ventricle, presenting in early infancy with progressive hemiparesis, severe psychomotor retardation and intractable seizures. Hemimegalencephaly may be an isolated finding or associated with other syndromes such as angioosteohypertrophic syndrome, epidermal nevus syndrome and Ito hypomelanosis. Management includes seizure control by antiepileptic medications and early hemispherectomy."
      },
      "child_count": 0,
      "reference_id": "MONDO:0020492"
    }
  ],
  "roots": [
    {
      "id": 19709,
      "label": "central nervous system malformation"
    }
  ]
}