Gut Microbiota in Monozygotic Twins Original paper

What was studied?

This study (“Parkinson’s disease in monozygotic twins” by Jankovic and Reches, 1986) investigated the occurrence and characteristics of Parkinson’s disease (PD) in a pair of monozygotic (identical) twins. The research was prompted by previous twin studies reporting a notably low concordance rate for PD among monozygotic twins, suggesting that genetic susceptibility might play a limited role. Contrary to these earlier findings, the authors describe a pair of twins, separated for forty years and living in different environments, who both developed typical, tremor-dominant, levodopa-responsive PD at age 71, with symptom onset occurring only three months apart. The study provides a detailed clinical, familial, and genetic profile of the twins and discusses the implications for genetic versus environmental contributions to PD, particularly concerning disease subtypes.

Who was studied?

The subjects were a male pair of monozygotic twins, born in Austria and aged 76 at the time of the study. They lived together until their early twenties and then apart in the United States and Israel, respectively, for forty years. Both had identical physical appearance and personalities, confirmed monozygosity through HLA and red blood cell antigen matching (99.5% certainty), and no family history of Parkinson’s or related neurodegenerative disease among close or distant relatives. Both twins were nonsmokers, had similar childhood illnesses and immunizations, and worked in retail. Their medical histories included three years in concentration camps during World War II. Both developed classic Parkinsonian symptoms at age 71, with identical disease progression and clinical presentation, and both responded well to levodopa treatment.

Most important findings

The most significant finding is the concordance for typical, tremor-dominant Parkinson’s disease in monozygotic twins, with nearly simultaneous onset after decades apart. This observation challenges previous twin studies that found very low concordance rates for PD in identical twins. The clinical course in both twins was virtually identical, including rest tremor, bradykinesia, rigidity, stooped posture, mild cognitive impairment, and hypokinetic dysarthria, all responsive to dopaminergic therapy. No environmental or familial factors could be attributed as common triggers, strengthening the case for genetic susceptibility in this PD subtype.

The study discusses the broader context of PD heterogeneity, noting that tremor-dominant forms tend to show a higher familial occurrence and potentially greater heritability. In contrast, other subtypes, such as those dominated by postural instability and gait dysfunction (PIGD), do not show this familial clustering. The authors also explore possible genetic mechanisms, including associations with essential tremor, hepatic detoxification defects, and lack of specific HLA haplotypes, but emphasize that no clear dominant inheritance pattern has been established for PD overall.

Although this study does not directly address the gut-brain axis or microbiome, it is highly relevant for a microbiome signatures database because it highlights the strong genetic component in specific PD subtypes, suggesting that microbiome studies in PD should consider disease heterogeneity and genetic background. It also raises the possibility that environmental exposures (potentially including microbiome-derived factors) may have more or less influence depending on the patient’s genetic susceptibility.

Key implications

The findings underscore the importance of genetic factors in the etiology of tremor-dominant Parkinson’s disease, even in the context of divergent life experiences and environmental exposures. This supports the concept that PD is a heterogeneous disorder, with some subtypes (such as tremor-dominant PD) exhibiting stronger genetic underpinnings. For clinicians and researchers, this means that genetic susceptibility, family history, and disease phenotype should all be considered when evaluating PD patients, interpreting epidemiological data, and designing studies—including those investigating the role of the microbiome. For microbiome research specifically, it suggests that patient stratification by genetic background and clinical subtype may be necessary to uncover meaningful associations and signatures.

Citation

Jankovic J, Reches A. Parkinson’s disease in monozygotic twins. Ann Neurol. 1986;19(4):405-408. doi:10.1002/ana.410190415