[Rare hereditary and acquired diseases with parkinson's syndrome]

Despite established clinical diagnostic criteria for Parkinson's disease and the neurodegeneration-related atypical parkinsonian syndromes (progressive supranuclear palsy/PSP, corticobasal degeneration syndrome/CBD, multiple system atrophy with parkinsonian or cerebellar predominance/MSA-P/C, and dementia with Lewy bodies/DLB), the differential diagnosis from rare hereditary and acquired disorders presenting with parkinsonism can be challenging.

Based on a PubMed search, relevant original studies and review articles were analyzed to identify rare hereditary and acquired disorders associated with parkinsonism. Secondary parkinsonian syndromes resulting from medication or toxin exposure were excluded but are summarized in an overview.

Without claiming completeness, the major hereditary and acquired disorders associated with parkinsonism were summarized in tabular form. Selected entities were described in more detail in short profiles focusing on those with therapeutic modifiability, characteristic pattern-like constellations of findings, or notable pathophysiological mechanisms. Paradigmatic cerebral MRI patterns are illustrated.

A broad spectrum of rare acquired and genetic entities can manifest with clinically relevant parkinsonian syndromes. Frequently, parkinsonism occurs in combination with other neurological features of variable severity, including extrapyramidal-hyperkinetic symptoms (dystonia/chorea), cerebellar signs (ataxia), pontomesencephalic involvement (oculomotor disturbances, bulbar dysarthria/dysphagia), motor neuron signs (spasticity and/or amyotrophic paresis), cognitive or neuropsychiatric symptoms, and epilepsy.For several disease groups - such as neurodegeneration with brain iron accumulation (NBIA), Wilson's disease, and primary familial brain calcification (PFBC) - distinctive MRI patterns are diagnostically informative.A relevant subset of disorders exhibits at least a partial and sometimes transient presynaptic dopaminergic deficit responsive to dopaminergic medication (e.g., certain NBIA forms, spinocerebellar ataxias/SCA, cerebrotendinous xanthomatosis/CTX).Neuropathologically, some of these disorders are associated with secondary synucleinopathies (e.g., MPAN), tauopathies (e.g., IgLON5 syndrome) or TDP-43 (e.g., Perry syndrome/DCTN1).