| Phenotype | Typical onset | Notes/frequency (if known) | Suggested HPO ID/label | Key supporting citations |
|---|---|---|---|---|
| Lissencephaly / pachygyria | Congenital / prenatal | Core feature of XLAG; often posterior-predominant lissencephaly or diffuse pachygyria with relatively mild cortical thickening | HP:0001339 Lissencephaly; HP:0001302 Pachygyria | (pqac-00000001, pqac-00000007, pqac-00000013, pqac-00000039) |
| Agenesis of the corpus callosum | Congenital / prenatal | Core feature of XLAG; in females with heterozygous ARX variants, ACC seen in 66.7% (24/36) who underwent MRI | HP:0001274 Agenesis of corpus callosum | (pqac-00000006, pqac-00000009, pqac-00000038, pqac-00000042) |
| Ambiguous / abnormal male genitalia | Congenital | Defining XLAG feature in affected 46,XY males; includes micropenis, cryptorchidism, hypoplastic external genitalia | HP:0000077 Abnormality of the genitalia; HP:0000054 Ambiguous genitalia; HP:0000046 Cryptorchidism; HP:0000054 Micropenis* | (pqac-00000003, pqac-00000008, pqac-00000010, pqac-00000041) |
| Neonatal-onset refractory seizures / epilepsy | Neonatal, often day 1 or within minutes–hours of life | Hallmark of XLAG; usually medically refractory/pharmacoresistant | HP:0002373 Febrile seizures**; HP:0001250 Seizures; HP:0012469 Neonatal seizures; HP:0001272 Cerebral visual impairment*** | (pqac-00000008, pqac-00000013, pqac-00000038, pqac-00000039) |
| Developmental and epileptic encephalopathy | Neonatal to infancy | Severe ARX spectrum includes Ohtahara/early infantile epileptic encephalopathy and infantile spasms; in de novo ARX females, 6/10 had DEE | HP:0100022 Developmental and epileptic encephalopathy | (pqac-00000012, pqac-00000014, pqac-00000015, pqac-00000043) |
| Infantile spasms / West syndrome | Infancy | Common in non-malformative severe ARX disorders and some female cases; part of broader severe ARX epilepsy spectrum | HP:0012469 Infantile spasms | (pqac-00000010, pqac-00000012, pqac-00000035, pqac-00000044) |
| Intellectual disability / global developmental delay | Infancy to childhood recognition | Severe developmental impairment is common; in females with heterozygous pathogenic ARX variants, 41% had severe ID/DEE | HP:0001249 Intellectual disability; HP:0001263 Global developmental delay | (pqac-00000009, pqac-00000012, pqac-00000014, pqac-00000015) |
| Postnatal / acquired microcephaly | Postnatal infancy | Reported in XLAG case series and pathology reports | HP:0000253 Microcephaly; HP:0005484 Postnatal microcephaly | (pqac-00000003, pqac-00000008) |
| Hypotonia | Neonatal / infancy | Common neurologic sign in severe ARX cases | HP:0001252 Hypotonia | (pqac-00000002, pqac-00000011, pqac-00000026) |
| Spasticity / spastic quadriparesis | Childhood, sometimes progressive | Reported in severe ARX phenotypes including XLAG-related and female severe cases | HP:0001257 Spasticity; HP:0001276 Spastic quadriplegia | (pqac-00000010, pqac-00000011, pqac-00000044) |
| Dystonia / hand dystonia | Childhood | Typical of polyalanine-expansion ARX disorders and Partington-spectrum disease; can coexist with epilepsy/ID | HP:0001332 Dystonia | (pqac-00000015, pqac-00000022, pqac-00000035) |
| Choreoathetoid / dyskinetic movements | Childhood | Reported in severe female ARX cases and broader severe ARX spectrum | HP:0001266 Choreoathetosis; HP:0001300 Abnormality of movement | (pqac-00000011, pqac-00000029) |
| Temperature instability / hypothalamic dysfunction | Neonatal / infancy | Recurrent associated XLAG feature; suggests hypothalamic involvement | HP:0002045 Hypothermia; HP:0012735 Temperature instability | (pqac-00000007, pqac-00000008, pqac-00000024) |
| Chronic diarrhea | Neonatal / infancy | Recurrent extra-neurologic XLAG feature; sometimes responsive to nutritional support | HP:0002014 Diarrhea; HP:0011968 Chronic diarrhea | (pqac-00000002, pqac-00000007, pqac-00000040) |
| Small basal ganglia / ganglionic eminence abnormalities on MRI | Prenatal / neonatal imaging | Characteristic imaging clue in ARX-related XLAG | HP:0012697 Abnormal basal ganglia MRI signal intensity**** | (pqac-00000005, pqac-00000013, pqac-00000038, pqac-00000053) |
| Three-layered cortex / interneuron deficit (neuropathology) | Prenatal developmental defect; recognized postmortem/pathology | Histopathologic hallmark supporting the “interneuronopathy” concept | HP:0012443 Abnormal cerebral cortex morphology***** | (pqac-00000000, pqac-00000020) |
| Autism spectrum disorder / learning difficulties in females | Childhood | In females with pathogenic ARX variants: 16.4% had isolated ACC or mild symptoms such as learning disabilities, ASD, or drug-responsive epilepsy without ID | HP:0000717 Autism; HP:0001328 Learning disability | (pqac-00000009) |


*Table: This table maps major neurologic and extra-neurologic features of ARX-related lissencephaly/interneuronopathy and related severe ARX disorders to suggested HPO terms. It is useful for structured disease annotation and phenotype harmonization in a knowledge base.*