| Phenotype (plain language) | Suggested HPO term(s) | Typical onset/course | Notes | Reported frequency (with numerator/denominator when available) | Most-associated subtype/gene | Key citation |
|---|---|---|---|---|---|---|
| Global developmental delay | HP:0001263 Global developmental delay | Infancy; usually persistent, non-progressive developmental impairment | Core feature across CAMRQ; often first recognized in infancy | 33/33 (100%) in compiled CAMRQ4 cohort | CAMRQ4 / ATP8A2 | (pqac-00000011, pqac-00000015) |
| Intellectual disability / impaired intellectual development | HP:0001249 Intellectual disability | Early childhood onward; persistent, severity variable | Often moderate to profound in VLDLR-DES; may be milder in some subtype-specific cases | 29/33 (88%) in CAMRQ4; moderate-to-profound commonly described in VLDLR-DES | All subtypes; especially CAMRQ1 / VLDLR and CAMRQ4 / ATP8A2 | (pqac-00000011, pqac-00000004, pqac-00000008) |
| Feeding difficulty | HP:0011968 Feeding difficulties | Infancy; may persist in severe cases | Common in severe CAMRQ4 and contributes to disability burden | 22/26 (85%) in CAMRQ4 | CAMRQ4 / ATP8A2 | (pqac-00000011, pqac-00000010) |
| Non-ambulatory / inability to walk independently | HP:0002540 Unable to walk; HP:0002509 Abnormality of gait | Infancy/childhood; usually chronic, some achieve limited ambulation | Delayed or absent walking is a defining feature; quadrupedal locomotion may occur in some families | 29/33 (88%) non-ambulatory in CAMRQ4; only 40% achieved ambulation at least once in another cohort | CAMRQ4 / ATP8A2; also seen in CAMRQ1-3 | (pqac-00000011, pqac-00000015, pqac-00000007) |
| Hypotonia | HP:0001252 Muscular hypotonia; HP:0001290 Generalized hypotonia | Neonatal/infantile onset; often persistent | Truncal hypotonia is particularly emphasized in VLDLR-DES and severe CAMRQ4 | 28/32 (88%) in CAMRQ4; 100% in one CAMRQ4 cohort | CAMRQ4 / ATP8A2; CAMRQ1 / VLDLR | (pqac-00000011, pqac-00000015, pqac-00000007) |
| Chorea / choreoathetosis / dyskinetic movements | HP:0002072 Chorea; HP:0001266 Choreoathetosis | Infancy or early childhood; persistent but variable | Helpful clue for CAMRQ4, sometimes mimics dyskinetic cerebral palsy early on | 22/27 (81%) in CAMRQ4; abnormal movements 50% in one cohort | CAMRQ4 / ATP8A2 | (pqac-00000011, pqac-00000010, pqac-00000015) |
| Lack of sitting and/or head control | HP:0001270 Motor delay; HP:0002429 Complete lack of development of motor skills; HP:0010869 Inability to lift head | Infancy; persistent in severe cases | Marker of severe neuromotor involvement | 20/30 (73%) in CAMRQ4 | CAMRQ4 / ATP8A2 | (pqac-00000011, pqac-00000010) |
| Cerebellar ataxia / truncal ataxia / disequilibrium | HP:0001251 Ataxia; HP:0002066 Gait ataxia; HP:0002078 Truncal ataxia | Congenital or infancy-onset; usually non-progressive or slowly evolving | Core syndrome-defining feature across all CAMRQ subtypes | 17/20 (85%) in CAMRQ4; 100% in one CAMRQ4 cohort | All subtypes; classic in CAMRQ1 / VLDLR | (pqac-00000011, pqac-00000015, pqac-00000004) |
| Optic atrophy / visual pathway involvement | HP:0000648 Optic atrophy | Childhood; may emerge over time | More prominent in ATP8A2-related disease than in classic VLDLR-DES | 16/27 (59%) in CAMRQ4 | CAMRQ4 / ATP8A2 | (pqac-00000011, pqac-00000010) |
| Ophthalmoplegia / abnormal eye movements | HP:0000602 Ophthalmoplegia; HP:0000508 Abnormality of eye movement | Infancy/childhood; persistent | Ocular motor abnormalities are recurrent in CAMRQ4 and abnormal ocular movements are also reported in DES broadly | 13/26 (50%) in CAMRQ4 | CAMRQ4 / ATP8A2 | (pqac-00000011, pqac-00000010, pqac-00000002) |
| Seizures | HP:0001250 Seizure | Variable; may occur in childhood | Not universal; historically reported in VLDLR-DES cohorts, absent in some later pedigrees | ~40% in reviewed VLDLR-DES patients | CAMRQ1 / VLDLR | (pqac-00000008, pqac-00000007) |
| Short stature | HP:0004322 Short stature | Childhood; persistent | Minor but reported associated feature in VLDLR-DES | ~15% in reviewed VLDLR-DES patients | CAMRQ1 / VLDLR | (pqac-00000008) |
| Cerebellar atrophy on MRI | HP:0001272 Cerebellar atrophy | Usually detected in childhood imaging; may be absent early | More variable in ATP8A2 disease than in VLDLR-DES; some CAMRQ4 patients have normal MRI | 6/31 (19%) in CAMRQ4 | CAMRQ4 / ATP8A2 | (pqac-00000011, pqac-00000015) |
| Cerebral atrophy on MRI | HP:0002059 Cerebral atrophy | Variable | Seen in a minority of CAMRQ4 cases | 5/31 (16%) in CAMRQ4 | CAMRQ4 / ATP8A2 | (pqac-00000011) |
| Thin / hypotrophic corpus callosum on MRI | HP:0002079 Hypoplasia of the corpus callosum; HP:0001273 Agenesis of corpus callosum (broader differential) | Variable; developmental structural finding | Reported in CAMRQ4 and CAMRQ2; may accompany white matter changes | 5/31 (16%) in CAMRQ4 | CAMRQ4 / ATP8A2; CAMRQ2 / WDR81 | (pqac-00000011, pqac-00000009, pqac-00000001) |
| Delayed myelination on MRI | HP:0002188 Delayed CNS myelination | Infancy/childhood | Supports neurodevelopmental disorder; not specific | 3/31 (10%) in CAMRQ4 | CAMRQ4 / ATP8A2 | (pqac-00000011, pqac-00000009, pqac-00000010) |
| Inferior cerebellar hypoplasia pattern on MRI | HP:0001321 Cerebellar hypoplasia; HP:0011329 Vermis hypoplasia | Congenital structural malformation; typically stable | Classic radiologic signature of VLDLR-DES involving inferior vermis and hemispheres | Qualitative hallmark; frequency not consistently enumerated in extracted text | CAMRQ1 / VLDLR | (pqac-00000004, pqac-00000008, pqac-00000017) |
| Pontine hypoplasia / small pons on MRI | HP:0007366 Small pons; HP:0001306 Pontine hypoplasia | Congenital structural malformation; typically stable | Often accompanies VLDLR-related cerebellar hypoplasia | Qualitative hallmark; frequency not consistently enumerated in extracted text | CAMRQ1 / VLDLR | (pqac-00000004, pqac-00000008, pqac-00000017) |
| Simplified gyration / cortical sulcal simplification on MRI | HP:0009879 Simplified gyral pattern; HP:0009875 Abnormal cerebral gyration | Congenital developmental brain malformation | In VLDLR-DES, cortical sulcation is simplified with mildly thickened cortex | Qualitative hallmark; frequency not consistently enumerated in extracted text | CAMRQ1 / VLDLR | (pqac-00000004, pqac-00000008, pqac-00000017) |


*Table: This table summarizes the most consistently reported clinical and MRI phenotypes across CAMRQ/dysequilibrium syndrome, with HPO mappings and subtype associations. It emphasizes quantitative frequencies from CAMRQ4 cohorts and the classic neuroradiologic pattern of VLDLR-associated disease.*