Parkinsonism and Other Movement Disorders Associated with Chediak‐Higashi Syndrome: Case Report and Systematic Literature Review

Chediak-Higashi syndrome (CHS) is a rare, autosomal recessive disorder resulting from mutations of the lysosomal trafficking regulator (LYST) gene. Dysfunction of LYST leads to disruption of transport and fusion of lysosomes and similar organelles. This reflects in the characteristic features of (partial) albinism, if melanin is not transported to the keratinocytes; bleeding diathesis, as a result of impairment of the thrombocytic granula; and immunodeficiency, mainly because of a lack of perforin mediated cytotoxicity. The severity of symptoms varies greatly and depends on the remaining function of LYST (genotype-phenotype correlation). Accordingly, the spectrum of CHS spans from childhood onset and a “mainly hematological,” potentially lethal disease course to the rarer variant of adulthood onset with slowly progressive neurodegeneration and only minor or no hematological disturbances (see Table 1). However, there is an overlap and the majority (~75%) of the cases with the later, neurological presentation do also featue immunodeficiency and/or bleeding diathesis. Here, we present a case of CHS with juvenile onset of parkinsonism with video documentation of the typical features and review existing literature of movement disorder presentations of CHS. The review is based on a PubMed search for articles in English, Spanish, or German with the terms Chediak-Higashi Syndrome, neurological, parkinsonism, tremor, ataxia, dystonia, myoclonus, tics, chorea, and a combination of these. Publications were included if sufficient evidence for a diagnosis of CHS (characteristic blood smear or gene mutation) was present; enough information of neurological status was provided; and when the neurological manifestation was not a result of lymphohistocytic infiltration.