| Phenotype | Suggested HPO term(s) | Onset / frequency / notes | Evidence sources |
|---|---|---|---|
| Hydrocephalus / ventriculomegaly | HP:0000238 Hydrocephalus; HP:0002119 Ventriculomegaly | Often prenatal or congenital; may begin in utero and range from severe fetal hydrocephalus to milder ventricular enlargement; core hallmark of L1 syndrome/HSAS (pqac-00000004, pqac-00000018, pqac-00000022) | (pqac-00000004, pqac-00000018, pqac-00000022) |
| Aqueductal stenosis | HP:0002620 Stenosis of the cerebral aqueduct | Classic feature of HSAS/X-linked hydrocephalus; commonly inferred from prenatal/postnatal neuroimaging and disease definition (pqac-00000004, pqac-00000024, pqac-00000025) | (pqac-00000004, pqac-00000024, pqac-00000025) |
| Corpus callosum agenesis / hypoplasia | HP:0001274 Agenesis of the corpus callosum; HP:0002079 Hypoplasia of the corpus callosum | Frequently detected prenatally or congenitally; part of CRASH/L1 spectrum; may be complete or partial (pqac-00000004, pqac-00000018, pqac-00000019, pqac-00000022) | (pqac-00000004, pqac-00000018, pqac-00000019, pqac-00000022) |
| Adducted thumbs | HP:0001182 Adducted thumb | Characteristic but not universal; reported in ~45% of cases in a foundational review; can sometimes be detected prenatally (pqac-00000004, pqac-00000018, pqac-00000026) | (pqac-00000004, pqac-00000018, pqac-00000026) |
| Spastic paraplegia / spasticity | HP:0001258 Spasticity; HP:0007021 Spastic paraplegia | Usually childhood-onset in SPG1/MASA end of spectrum; chronic motor disability affecting gait and mobility; severity variable (pqac-00000004, pqac-00000038, pqac-00000040) | (pqac-00000004, pqac-00000038, pqac-00000040) |
| Intellectual disability / developmental delay | HP:0001249 Intellectual disability; HP:0001263 Global developmental delay | Common across the spectrum; severity ranges from mild learning impairment to severe developmental disability (pqac-00000004, pqac-00000005, pqac-00000030) | (pqac-00000004, pqac-00000005, pqac-00000030) |
| Aphasia / speech impairment | HP:0002381 Aphasia; HP:0002167 Delayed speech and language development | Included in MASA acronym; speech/language impairment may be part of milder surviving phenotypes (pqac-00000002, pqac-00000038) | (pqac-00000002, pqac-00000038) |
| Shuffling gait / gait abnormality | HP:0002362 Shuffling gait; HP:0001288 Gait disturbance | Included in MASA acronym; usually reflects corticospinal tract dysfunction/spastic paraparesis with childhood onset or progressive mobility limitation (pqac-00000002, pqac-00000038, pqac-00000034) | (pqac-00000002, pqac-00000038, pqac-00000034) |
| White matter abnormalities / hypomyelination | HP:0002500 Abnormal cerebral white matter morphology; HP:0003429 Hypomyelination | Reported as reduced white matter / hypomyelination in L1 spectrum and model data; may contribute to motor/cognitive dysfunction (pqac-00000003, pqac-00000024, pqac-00000037) | (pqac-00000003, pqac-00000024, pqac-00000037) |
| Corticospinal tract hypoplasia | HP:0031887 Corticospinal tract hypoplasia | Described as part of the core neuroanatomic spectrum and likely underlies spastic paraplegia/spastic gait (pqac-00000004, pqac-00000030) | (pqac-00000004, pqac-00000030) |
| Macrocephaly | HP:0000256 Macrocephaly | May accompany ventriculomegaly/hydrocephalus, especially in affected males; secondary to CSF accumulation rather than a universal primary trait (pqac-00000003, pqac-00000030) | (pqac-00000003, pqac-00000030) |
| Dilated third ventricle (prenatal ultrasound/MRI finding) | HP:0003370 Enlarged third ventricle | Prenatal imaging clue; reported with severe fetal hydrocephalus/ventriculomegaly and corpus callosum anomalies (pqac-00000018, pqac-00000021, pqac-00000023) | (pqac-00000018, pqac-00000021, pqac-00000023) |
| Absent cavum septum pellucidum (prenatal imaging finding) | HP:0012113 Absent septum pellucidum | Prenatal imaging clue that may accompany corpus callosum agenesis and ventriculomegaly in affected male fetuses (pqac-00000019, pqac-00000021) | (pqac-00000019, pqac-00000021) |


*Table: This table maps the principal clinical and prenatal imaging features of L1 syndrome to suggested HPO terms, with brief notes on onset and frequency where available. It is useful for structured phenotype annotation in a disease knowledge base.*