Objective: We describe a family with 4 members affected by PD, carrying a new variant of the LRRK2 gen, with anticipation phenomenon in succeding generation.

Background: LRRK2 mutations are the most common cause of autosomal dominant (AD) familial PD. The phenotype described is very similar to idiopathic Parkinson’s disease (IPD), with a mean onset of symptoms in 56-59 years (1).

Method: Index patient: a 39-year-old female patient consulted for tremor, stiffness and dystonia in the left extremities. She was diagnosed with early-onset PD (EOPD), and she began dopaminergic therapy with good response. One sister of the patient (36 years old) consulted for pain, discomfort and paresthesia focused on MSI, being diagnosed with EOPD. They have 2 older brothers without parkinsonian symptoms. Their father and paternal aunt began at 64 years of age with parkinsonian symptoms in the left half of the body. Both were diagnosed of PD and showed a good response to dopaminergic medication. The father developed an ICD (gambling) that was partially controlled by suspending dopaminergic agonists. One older aunt (68 y) began with tremor in left upper extremity. The index patient has been recently implanted with bilateral STN-DBS because of severe motor fluctuations.

Results: Index patient: Metabolic study of copper, TSH, B12 and folic: normal. Brain MRI: normal. SPECT with DAT-Scan: absence of uptake in the bilateral putamen, decreased uptake in the right caudate. Genetic study: Variant of uncertain clinical significance in heterozygosity; c.4001G> A (p.Arg1334Gln) in the LRRK2 gene. Its frequency in the 1000 genome’s database is 0. It was considered to be ’cause of disease’ by Mutation taster, and ‘probably harmful’ by Polyphen2.
SPECT with DAT-Scan of sister, father and paternal aunt: absence of uptake in the bilateral putamen, decreased uptake in the right caudate. Brain MRI of sister, father and paternal aunt: normal. Genetic study of sister, father and paternal aunt: Variant of uncertain clinical significance in heterozygosity; c.4001G> A (p.Arg1334Gln) in the LRRK2 gene. Genetic study of the older paternal aunt: pending.

Conclusion: We describe a family with Parkinson’s disease AD associated with a new mutation in the LRRK2 gene, possibly pathogenic. Symptoms began at a younger age in second-generation patients, which could suggest a phenomenon of anticipation

References: 1. CHaugarvoll K, Wszolek ZK. Clinical features of LRRK2 parkinsonism. Parkinsonism Relat Disord. 2009 Dec;15 Suppl 3:S205-8

« Back to MDS Virtual Congress 2021

MDS Abstracts - https://www.mdsabstracts.org/abstract/familial-parkinsons-disease-pd-with-anticipation-phenomenon-undescribed-variant-in-the-lrrk2-gene-c-4001g-a-p-arg1334gln/