{
  "id": 18774,
  "label": "lissencephaly spectrum disorders",
  "model": {
    "label": "Mondo Disease Ontology (MONDO)",
    "source": 0
  },
  "type_id": 0,
  "reference_id": "MONDO:0018838",
  "properties": {
    "xrefs": [
      "DOID:0050453",
      "GARD:0012291",
      "HP:0001339",
      "MEDGEN:78604",
      "MESH:D054082",
      "MedDRA:10048911",
      "NANDO:1200574",
      "NANDO:2200817",
      "NCIT:C103921",
      "NORD:1374",
      "OMIMPS:607432",
      "Orphanet:48471",
      "SCTID:204036008",
      "UMLS:C0266463"
    ],
    "synonyms": [
      "Lissencephaly",
      "lissencephaly",
      "lissencephaly (disease)",
      "lissencephaly spectrum disorders",
      "Broad gyri of cerebrum",
      "large gyri of cerebrum",
      "macrogyria",
      "pachygyria"
    ],
    "categories": [
      {
        "ref": "MONDO:0005071",
        "name": "nervous system disorder"
      }
    ],
    "definition": "The term lissencephaly covers a group of rare malformations sharing the common feature of anomalies in the appearance of brain convolutions (characterized by simplification or absence of folding) associated with abnormal organization of the cortical layers as a result of neuronal migration defects during embryogenesis."
  },
  "isLeaf": false,
  "isRoot": false,
  "child_count": 14,
  "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": 20383,
      "label": "disorder of development or morphogenesis",
      "isLeaf": false,
      "isRoot": false,
      "parents": [
        29380
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "ICD10CM:Q00-Q99",
          "MEDGEN:1843482",
          "UMLS:C0694457"
        ],
        "definition": "Any disease or disorder that disrupts the process development of an anatomical structure. Can be due to genetic or environmental causes. Typically happens during embryogenesis, but also includes post-embryonic development."
      },
      "child_count": 190,
      "reference_id": "MONDO:0021147"
    },
    {
      "id": 24270,
      "label": "hereditary neurological disease",
      "isLeaf": false,
      "isRoot": false,
      "parents": [
        5714,
        6799
      ],
      "type_id": 0,
      "properties": {
        "synonyms": [
          "neurogenetic disease"
        ],
        "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 characterized by abnormalities in the brain, spinal cord, nerves, or muscles."
      },
      "child_count": 528,
      "reference_id": "MONDO:0100545"
    }
  ],
  "children": [
    {
      "id": 10293,
      "label": "craniotelencephalic dysplasia",
      "isLeaf": true,
      "isRoot": false,
      "parents": [
        16201,
        18774
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "GARD:0001605",
          "MEDGEN:347462",
          "MESH:C535597",
          "OMIM:218670",
          "Orphanet:1528",
          "SCTID:715422002",
          "UMLS:C1857471",
          "icd11.foundation:1684038717"
        ],
        "synonyms": [
          "craniotelencephalic dysplasia",
          "Complex of anomalies involving the cranium and brain"
        ],
        "categories": [
          {
            "ref": "MONDO:0002081",
            "name": "musculoskeletal system disorder"
          },
          {
            "ref": "MONDO:0002254",
            "name": "syndromic disease"
          },
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ],
        "definition": "Craniotelencephalic dysplasia is an extremely rare, genetic developmental defect during embryogenesis syndrome characterized by craniosynostosis with frontal encephalocele and various additional brain anomalies (severe hydrocephalus, agenesis of the corpus callosum, lissencephaly and polymicrogyria, parenchymal cysts, septo-optic dysplasia) resulting in marked cerebral dysfunction, seizures and very severe psychomotor delay. There have been no further descriptions in the literature since 1983."
      },
      "child_count": 0,
      "reference_id": "MONDO:0009042"
    },
    {
      "id": 11442,
      "label": "X-linked lissencephaly with abnormal genitalia",
      "isLeaf": true,
      "isRoot": false,
      "parents": [
        2902,
        4370,
        18774
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "DOID:0112238",
          "GARD:0012491",
          "MEDGEN:375832",
          "MESH:C564563",
          "OMIM:300215",
          "Orphanet:452",
          "SCTID:717632002",
          "UMLS:C1846171"
        ],
        "synonyms": [
          "X-linked lissencephaly with abnormal genitalia",
          "X-linked lissencephaly with ambiguous genitalia",
          "X-linked lissencephaly-agenesis of the corpus callosum-genital anomalies syndrome",
          "X-linked lissencephaly-corpus callosum agenesis-genital anomalies syndrome",
          "XLAG (X-linked lissencephaly with abnormal genitalia) syndrome",
          "lissencephaly, X-linked, type 2",
          "LISX2",
          "X-linked lissencephaly - agenesis of the corpus callosum - genital anomalies",
          "XLAG syndrome",
          "Xlisg",
          "hydranencephaly and abnormal genitalia",
          "hydranencephaly with abnormal genitalia",
          "lissencephaly, X-linked 2",
          "lissencephaly, X-linked, 2",
          "lissencephaly, X-linked, with ambiguous genitalia"
        ],
        "categories": [
          {
            "ref": "MONDO:0002254",
            "name": "syndromic disease"
          },
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ],
        "definition": "X-linked lissencephaly with abnormal genitalia (XLAG) is a severe neurological disorder that only manifests in genotypic males and includes lissencephaly with posterior-to-anterior gradient and only moderate increase in thickness of the cortex, absent corpus callosum, neonatal-onset severe epilepsy, hypothalamic dysfunction including defective temperature regulation, and ambiguous genitalia with micropenis and cryptorchidism. XLAG differs considerably from classical lissencephaly, as the resulting cortical thickness is only 6-7 mm in XLAG, rather than 15-20 mm seen in classical lissencephaly due to mutations of the PAFAH1B1 or DCX genes. In 2002, mutations in the X-linked aristaless-related homeobox gene (ARX ; Xp21.3) were identified in individuals with XLAG and in some of their female relatives. Mouse Arx and human ARX are highly expressed in both dorsal and ventral telencephalon, including the neocortical ventricular zone and germinal zone of the ganglionic eminence, with less intense signals in the subventricular zone, cortical plate, hippocampus, basal ganglia and ventral thalamus. Arx-deficient mice showed deficient tangential migration and abnormal differentiation of GABAergic interneurons in the ganglionic eminence and neocortex, as well as abnormal testicular differentiation. These characteristics include some of the clinical features of XLAG in humans. The ARX mutations in XLAG patients were predominantly premature termination mutations (large deletions, frameshift, nonsense mutations, splice site mutations) while the missense mutations were less common and located essentially in the homeobox domain. Patients carrying nonconservative missense mutations within the homeobox, showed less severe XLAG, while conservative substitution in the homeodomain caused Proud syndrome (ACC with abnormal genitalia). A non conservative missense mutation near the C-terminal aristaless domain caused unusually severe XLAG with microcephaly and mild cerebellar hypoplasia. The ARX mutations are also associated with a spectrum of milder phenotypes, without macroscopic malformations of the brain, such as X-linked infantile spasms, a syndrome featuring mental retardation associated with distal dystonic movements (Partington syndrome), autistic features and nonsyndromicintellectual deficit."
      },
      "child_count": 0,
      "reference_id": "MONDO:0010268"
    },
    {
      "id": 15594,
      "label": "lissencephaly 7 with cerebellar hypoplasia",
      "isLeaf": true,
      "isRoot": false,
      "parents": [
        18774
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "DOID:0112231",
          "GARD:0025004",
          "MEDGEN:895680",
          "OMIM:616342",
          "UMLS:C4225359"
        ],
        "synonyms": [
          "lissencephaly 7 with cerebellar hypoplasia",
          "LIS7"
        ],
        "categories": [
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ]
      },
      "child_count": 0,
      "reference_id": "MONDO:0014596"
    },
    {
      "id": 15968,
      "label": "lissencephaly 8",
      "isLeaf": true,
      "isRoot": false,
      "parents": [
        18774
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "DOID:0112233",
          "GARD:0025044",
          "MEDGEN:934613",
          "OMIM:617255",
          "UMLS:C4310646"
        ],
        "synonyms": [
          "LIS8",
          "TMTC3 lissencephaly (disease)",
          "lissencephaly (disease) caused by mutation in TMTC3",
          "lissencephaly 8",
          "lissencephaly 8; LIS8",
          "lissencephaly type 8"
        ],
        "categories": [
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ],
        "definition": "Any lissencephaly (disease) in which the cause of the disease is a mutation in the TMTC3 gene."
      },
      "child_count": 0,
      "reference_id": "MONDO:0014992"
    },
    {
      "id": 16079,
      "label": "classic lissencephaly",
      "isLeaf": false,
      "isRoot": false,
      "parents": [
        18774
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "GARD:0005049",
          "MEDGEN:98463",
          "NANDO:1201068",
          "NANDO:1201069",
          "Orphanet:102009",
          "UMLS:C0431375",
          "icd11.foundation:570001324"
        ],
        "synonyms": [
          "lissencephaly type 1",
          "ILS",
          "lissencephaly classic",
          "lissencephaly sequence isolated"
        ],
        "categories": [
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ]
      },
      "child_count": 4,
      "reference_id": "MONDO:0015146"
    },
    {
      "id": 16080,
      "label": "lissencephaly type 3",
      "isLeaf": false,
      "isRoot": false,
      "parents": [
        18774
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "DOID:0112232",
          "GARD:0019821",
          "MEDGEN:369910",
          "Orphanet:102011",
          "UMLS:C1969029",
          "icd11.foundation:1533765623"
        ],
        "categories": [
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ]
      },
      "child_count": 4,
      "reference_id": "MONDO:0015148"
    },
    {
      "id": 16115,
      "label": "microlissencephaly",
      "isLeaf": false,
      "isRoot": false,
      "parents": [
        18774
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "DOID:0112234",
          "GARD:0016555",
          "MEDGEN:365439",
          "Orphanet:1083",
          "UMLS:C1956147",
          "icd11.foundation:169315445"
        ],
        "categories": [
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ],
        "definition": "Microlissencephaly describes a heterogenous group of a rare cortical malformations characterized by lissencephaly in combination with severe congenital microcephaly, presenting with spasticity, severe developmental delay, and seizures and with survival varying from days to years."
      },
      "child_count": 3,
      "reference_id": "MONDO:0015204"
    },
    {
      "id": 17118,
      "label": "Warburg micro syndrome",
      "isLeaf": false,
      "isRoot": false,
      "parents": [
        7611,
        16087,
        18774,
        24642
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "DOID:0060237",
          "GARD:0005534",
          "MEDGEN:1781286",
          "NORD:1898",
          "OMIMPS:600118",
          "Orphanet:2510",
          "UMLS:C5442005"
        ],
        "synonyms": [
          "WARBM",
          "Warburg micro syndrome",
          "micro syndrome",
          "microcephaly, microcornea, congenital cataract, intellectual disability, optic atrophy and hypogenitalism",
          "microcephaly, microcornea, congenital cataract, mental retardation, optic atrophy and hypogenitalism"
        ],
        "categories": [
          {
            "ref": "MONDO:0002022",
            "name": "disorder of orbital region"
          },
          {
            "ref": "MONDO:0002254",
            "name": "syndromic disease"
          },
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          },
          {
            "ref": "MONDO:0024458",
            "name": "disorder of visual system"
          }
        ],
        "definition": "Micro syndrome is an autosomal recessive disorder caracterised by ocular and neurodevelopmental defects and by microgenitalia. It presents with severe intellectual disability, microcephaly, congenital cataract, microcornea, microphthalmia, agenesis/hypoplasia of the corpus callosum, and hypogenitalism."
      },
      "child_count": 16,
      "reference_id": "MONDO:0016649"
    },
    {
      "id": 17860,
      "label": "Baraitser-Winter cerebrofrontofacial syndrome",
      "isLeaf": false,
      "isRoot": false,
      "parents": [
        4370,
        16087,
        18774
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "DOID:0060229",
          "GARD:0005279",
          "ICD9:759.89",
          "MEDGEN:340016",
          "OMIMPS:243310",
          "Orphanet:2995",
          "SCTID:702410002",
          "UMLS:C1853623"
        ],
        "synonyms": [
          "Baraitser-Winter syndrome",
          "BRWS",
          "Fryns-Aftimos syndrome",
          "cerebro-frontofacial syndrome, type 3",
          "iris coloboma with ptosis hypertelorism and intellectual disability",
          "iris coloboma with ptosis hypertelorism and mental retardation",
          "trigonocephaly ptosis coloboma",
          "trigonocephaly ptosis intellectual disability",
          "trigonocephaly ptosis mental retardation"
        ],
        "categories": [
          {
            "ref": "MONDO:0002254",
            "name": "syndromic disease"
          },
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ],
        "definition": "Baraitser-Winter syndrome (BWS) is a malformation syndrome, characterized by facial dysmorphism (hypertelorism with ptosis, broad bulbous nose, ridged metopic suture, arched eyebrows, progressive coarsening of the face), ocular coloboma, pachygyria and/or band heterotopias with antero-posterior gradient, progressive joint stiffening, and intellectual deficit of variable severity, often with severe epilepsy. Pachygyria - epilepsy - intellectual disability - dysmorphism (Fryns-Aftimos syndrome (FA)) corresponds to the appearance of BWS in elderly patients."
      },
      "child_count": 6,
      "reference_id": "MONDO:0017579"
    },
    {
      "id": 18801,
      "label": "cobblestone lissencephaly",
      "isLeaf": false,
      "isRoot": false,
      "parents": [
        18774
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "GARD:0003277",
          "MEDGEN:96562",
          "MESH:D054222",
          "NANDO:1201072",
          "Orphanet:51577",
          "SCTID:253149002",
          "UMLS:C0431376"
        ],
        "synonyms": [
          "lissencephaly type 2"
        ],
        "categories": [
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ],
        "definition": "Cobblestone lissencephaly is a rare central nervous system malformation which includes a group of diseases that are characterized by a bumpy (or pebbled) appearance of the cerebral cortex, associated with a thickened cortex, reduction in normal sulcation, ventriculomegaly and reduced, abnormal white matter, as well as brainstem and cerebellum hypoplasia and corpus callosum agenesis. Patients generally present variable degrees of developmental delay, hypotonia and ocular abnomalities, however muscular and ocular involvement may be absent."
      },
      "child_count": 2,
      "reference_id": "MONDO:0018869"
    },
    {
      "id": 19276,
      "label": "lissencephaly with cerebellar hypoplasia",
      "isLeaf": false,
      "isRoot": false,
      "parents": [
        18774
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "GARD:0019068",
          "MEDGEN:905529",
          "Orphanet:86823",
          "SCTID:715817007",
          "UMLS:C4274995",
          "icd11.foundation:649858830"
        ],
        "synonyms": [
          "LCH"
        ],
        "categories": [
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ],
        "definition": "Lissencephaly with cerebellar hypoplasia (LCH) is a variant form of lissencephaly and involves a heterogeneous group of cortical malformations without severe congenital microcephaly (>-3 SD). LCH is characterized by cerebellar underdevelopment ranging from vermian hypoplasia to total aplasia with classical or cobblestone lissencephaly. The phenotypic features of LCH include small head circumference (between -2 and -3 standard deviations (SD) forage) at birth and postnatally, moderate to severe intellectual disability, hypotonia and spasticity. Seizures are often observed and infantile spasms have been reported in some rare cases. LCH has been classified into six subgroups according to neuroradiographic properties and are classified LCH type A to F."
      },
      "child_count": 6,
      "reference_id": "MONDO:0019450"
    },
    {
      "id": 21814,
      "label": "lissencephaly 10",
      "isLeaf": true,
      "isRoot": false,
      "parents": [
        18774
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "DOID:0112229",
          "GARD:0025512",
          "MEDGEN:1719546",
          "OMIM:618873",
          "UMLS:C5394354"
        ],
        "synonyms": [
          "LIS10",
          "LISSENCEPHALY 10",
          "lissencephaly 10"
        ],
        "categories": [
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ]
      },
      "child_count": 0,
      "reference_id": "MONDO:0030031"
    },
    {
      "id": 23132,
      "label": "massa casaer ceulemans syndrome",
      "isLeaf": true,
      "isRoot": false,
      "parents": [
        10051,
        18774
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "GARD:0003407",
          "MEDGEN:418986",
          "MESH:C536031",
          "UMLS:C2931090"
        ],
        "synonyms": [
          "arthrogryposis multiplex congenita associated with lissencephaly"
        ],
        "categories": [
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ]
      },
      "child_count": 0,
      "reference_id": "MONDO:0043123"
    },
    {
      "id": 24198,
      "label": "lissencephaly spectrum disorder with complex brainstem malformation",
      "isLeaf": false,
      "isRoot": false,
      "parents": [
        18774
      ],
      "type_id": 0,
      "properties": {
        "xrefs": [
          "GARD:0026233"
        ],
        "categories": [
          {
            "ref": "MONDO:0005071",
            "name": "nervous system disorder"
          }
        ],
        "definition": "A lissencephaly spectrum disorder that manifests as posterior predominant pachygyria (ranging from mild severity to classic lissencephaly) and brainstem malformations which include brainstem dysplasia (typically with reduced anteroposterior thickness and transverse broadening of the pons/medulla) and midline crossing defects (anterior commissure, transverse pontine fibers, pyramidal tract, callosum hypoplasia)."
      },
      "child_count": 1,
      "reference_id": "MONDO:0100472"
    }
  ],
  "roots": [
    {
      "id": 4427,
      "label": "congenital nervous system disorder"
    },
    {
      "id": 20383,
      "label": "disorder of development or morphogenesis"
    },
    {
      "id": 24270,
      "label": "hereditary neurological disease"
    }
  ]
}