| Clinical feature | Phenotype type (symptom/sign/lab/pathology) | Typical timing (with any quantitative age data) | Notes (frequency if available) | Suggested HPO term(s) | Supporting citation IDs |
|---|---|---|---|---|---|
| Early cataracts / visual impairment | Sign / symptom | Usually first manifestation; often **before age 30**; median visual symptom onset **27 years** | Described as early and prominent in the original Danish pedigree; ophthalmic disease precedes neurologic decline by years to decades | HP:0000518 Cataract; HP:0000505 Visual impairment | (pqac-00000001, pqac-00000004, pqac-00000006) |
| Progressive hearing loss / deafness | Symptom / sign | Typically appears **10–20 years after ocular problems**; often severe by the **5th decade** | Major non-cognitive feature; contributes substantially to disability | HP:0000365 Hearing impairment; HP:0000407 Sensorineural hearing impairment | (pqac-00000001, pqac-00000004, pqac-00000006) |
| Cerebellar ataxia | Sign | Develops in adulthood after sensory manifestations; progressive | Core neurologic phenotype in reviews and case descriptions | HP:0001251 Ataxia; HP:0002060 Cerebellar ataxia | (pqac-00000001, pqac-00000002, pqac-00000004, pqac-00000006) |
| Intention tremor | Sign | Adult onset; accompanies cerebellar syndrome | Reported as part of the cerebellar phenotype | HP:0002080 Intention tremor; HP:0001337 Tremor | (pqac-00000001) |
| Progressive dementia / cognitive deterioration | Symptom / syndrome | Probably begins in the **6th decade**; chronic progressive course | Central late manifestation; disease is neurodegenerative and usually fatal | HP:0000726 Dementia; HP:0100543 Cognitive impairment | (pqac-00000001, pqac-00000003, pqac-00000004, pqac-00000006) |
| Psychosis | Symptom / behavioral change | Adult onset; timing not well quantified in retrieved evidence | Reported in reviews, but frequency not available in current evidence set | HP:0000709 Psychosis | (pqac-00000006) |
| Spasticity / spastic paralysis | Sign | Adult onset; progressive in advanced disease | Mentioned in review literature; severity likely increases with disease progression | HP:0001257 Spasticity; HP:0007020 Spastic paraplegia | (pqac-00000006) |
| Gait abnormality / wide-based gait | Sign | Adult to later-stage disease; progressive | Seen clinically and recapitulated in transgenic/rat models; likely related to cerebellar and white-matter pathology | HP:0001288 Gait disturbance; HP:0002136 Wide-based gait | (pqac-00000002, pqac-00000027, pqac-00000028, pqac-00000029) |
| Motor dysfunction | Symptom / sign | Progressive with age; later-stage manifestation in both humans and models | Rat model links this to cerebellar ADan-CAA, demyelination, axonal loss, and fibrinogen leakage | HP:0004305 Motor delay/abnormality (general); HP:0001270 Motor impairment | (pqac-00000002, pqac-00000011, pqac-00000028) |
| White-matter abnormalities on neuroimaging | Imaging / pathology | Reported in symptomatic adults; timing not well quantified | Related imaging findings include **periventricular white-matter changes** and ventricular dilatation | HP:0002500 Abnormal cerebral white matter morphology; HP:0002119 Ventriculomegaly | (pqac-00000004) |
| Cerebral amyloid angiopathy (CAA), including retinal and cerebral vascular amyloid | Pathology | Progressive age-related accumulation over disease course | Major histopathologic hallmark; deposits are predominantly vascular, including retina and small cerebral vessels/capillaries | HP:0031630 Cerebral amyloid angiopathy; HP:0100651 Retinal vascular abnormality | (pqac-00000001, pqac-00000004, pqac-00000006) |
| Parenchymal ADan amyloid deposition | Pathology | Progressive; present in affected brain, though compact plaques may be absent | ADan is a 34-aa peptide derived from mutant ITM2B/BRI2; some reports emphasize pre-amyloid/non-compact deposits rather than classic plaques | HP:0011972 Amyloidosis; HP:0012759 Abnormality of CNS physiology/pathology | (pqac-00000001, pqac-00000004, pqac-00000032) |
| Co-deposition of Aβ with ADan | Pathology / biochemical | Detected in affected brain during established disease | Important mechanistic feature linking FDD to Alzheimer-like amyloid biology | HP:0011972 Amyloidosis | (pqac-00000001, pqac-00000005, pqac-00000007, pqac-00000032) |
| Neurofibrillary tangles / tau pathology | Pathology | Later-stage neurodegenerative pathology | Prominent in hippocampus and limbic structures; paired helical filaments reported | HP:0002185 Neurofibrillary tangles | (pqac-00000001, pqac-00000003, pqac-00000004) |
| Death / shortened survival | Outcome | Median age at death **58 years** in a series of **13 cases across 5 generations** | Indicates substantial mortality burden; no modern survival curves retrieved | HP:0003819 Premature death | (pqac-00000004) |


*Table: This table summarizes the major clinical and pathologic features reported for familial Danish dementia/ADan amyloidosis, including approximate timing and suggested HPO mappings. It is useful for disease knowledge-base curation and phenotype annotation.*