| Phenotype description | Suggested HPO term | Typical onset | Frequency / quantitative detail | Key supporting citation IDs |
|---|---|---|---|---|
| Congenital/postnatal microcephaly with OFC substantially below mean | HP:0000252 Microcephaly | Congenital or infancy | 3/3 in the original TUBB5 human series; OFC at birth −3 SD, −3 SD, and −4 SD; OFC at last evaluation about −2.5 to −4 SD (pqac-00000026, pqac-00000027) | (pqac-00000001, pqac-00000026, pqac-00000027) |
| Developmental delay / intellectual disability | HP:0001263 Global developmental delay; HP:0001249 Intellectual disability | Infancy | Present in all 3/3 TUBB5 cases in Breuss 2012, ranging from mild developmental delay to severe intellectual disability/mental retardation (pqac-00000026) | (pqac-00000001, pqac-00000026) |
| Motor delay | HP:0001270 Motor delay | Infancy | Present in 3/3 TUBB5 cases in Breuss 2012; Oegema cohort reports delayed psychomotor development in all 10/10, with motor development usually more affected than speech (pqac-00000022, pqac-00000026) | (pqac-00000002, pqac-00000022, pqac-00000026) |
| Speech/language delay | HP:0000750 Delayed speech and language development | Infancy to early childhood | Present in 3/3 TUBB5 cases in Breuss 2012 (severe language delay, limited language/speech delay, delayed speech) (pqac-00000026) | (pqac-00000001, pqac-00000026) |
| Abnormal cortical gyration / dysgyria, including focal polymicrogyria | HP:0002539 Polymicrogyria; HP:0031882 Abnormality of cerebral gyration | Prenatal / congenital structural anomaly | In Breuss 2012, 1/3 had focal polymicrogyria and localized band heterotopia; broader tubulinopathy imaging studies emphasize dysgyria as a recurring feature (pqac-00000023, pqac-00000026, pqac-00000027) | (pqac-00000009, pqac-00000023, pqac-00000026, pqac-00000027) |
| Corpus callosum abnormality (partial agenesis, thin/short callosum) | HP:0001274 Agenesis of corpus callosum; HP:0002079 Hypoplasia of the corpus callosum | Prenatal / congenital structural anomaly | 3/3 in Breuss 2012: partial agenesis, thin/short but complete, or partial posterior agenesis (pqac-00000026); small/absent corpus callosum is common across tubulinopathies (pqac-00000023) | (pqac-00000001, pqac-00000023, pqac-00000026, pqac-00000027) |
| Basal ganglia dysmorphism | HP:0002134 Abnormality of the basal ganglia | Prenatal / congenital structural anomaly | 3/3 in Breuss 2012 had dysmorphic basal ganglia; 10-patient hindbrain dysplasia cohort was ascertained for basal ganglia dysplasia pattern (pqac-00000022, pqac-00000026, pqac-00000027) | (pqac-00000002, pqac-00000022, pqac-00000026, pqac-00000027) |
| White matter streaks through lenticular nucleus / abnormal white matter pattern | HP:0002500 Abnormal cerebral white matter morphology | Prenatal / congenital structural anomaly | Seen in 2/3 Breuss 2012 cases (M299V and V353I) with characteristic streaks of white matter in/through basal ganglia region (pqac-00000026, pqac-00000027) | (pqac-00000001, pqac-00000026, pqac-00000027) |
| Brainstem hypoplasia / small pons | HP:0002365 Hypoplasia of the brainstem; HP:0007361 Small pons | Prenatal / congenital structural anomaly | Severe brainstem hypoplasia in at least 1/3 Breuss 2012 MRI-detailed cases; small pons/brainstem abnormalities are common in tubulinopathies broadly (pqac-00000023, pqac-00000027) | (pqac-00000009, pqac-00000023, pqac-00000027) |
| Cerebellar/vermis hypoplasia or dysplasia | HP:0001321 Cerebellar hypoplasia; HP:0001272 Cerebellar dysplasia | Prenatal / congenital structural anomaly | In Breuss 2012, 2/3 showed cerebellar/vermis abnormalities (hypoplastic/dysplastic vermis; large 4th ventricle suggesting posterior fossa involvement), and Oegema 2015 identified superior cerebellar dysplasia as a defining pattern in 10 patients (pqac-00000022, pqac-00000026) | (pqac-00000002, pqac-00000022, pqac-00000026) |
| Seizures / epilepsy | HP:0001250 Seizure | Infancy or childhood when present | Not a core feature in the original 3-patient TUBB5 series excerpt, but present in 4/10 in the imaging-defined hindbrain dysplasia cohort with TUBB among implicated genes (pqac-00000022) | (pqac-00000002, pqac-00000022) |
| Ocular motor abnormalities / strabismus / oculomotor apraxia | HP:0000646 Strabismus; HP:0000657 Oculomotor apraxia | Childhood | In Oegema 2015, abnormal eye movements in 7/10, oculomotor apraxia in 4/10, and strabismus in 5/10; one Breuss 2012 patient had micro-ophthalmia and retinal dysplasia (pqac-00000022, pqac-00000026) | (pqac-00000002, pqac-00000022, pqac-00000026) |
| Ataxia | HP:0001251 Ataxia | Early childhood | Reported in 1/3 TUBB5 cases in Breuss 2012 (patient with severe motor delay and ataxia) (pqac-00000026) | (pqac-00000001, pqac-00000026) |


*Table: This table maps the main reported clinical and neuroimaging features of TUBB5-related microcephaly to suggested HPO terms, with onset and quantitative frequencies where available. It is useful for knowledge-base curation and phenotype annotation grounded in the primary TUBB5 case series and related tubulinopathy cohorts.*