Objective: To report the clinical phenotype of an uncommon hereditary systemic disease with slowly progressive gait and movement disorder with genetic identification of two concurrent mitochondrial DNA mutations.

Background: Madelung disease (Benign symmetric lipomatosis) is a rare syndrome with multiple lipomas around the neck, upper limbs and trunk in the context of chronic alcoholism. Cases with neuropathy, myopathy and ataxia were described, relating some to mitochondrial mutations, but this association has been inconsistent.Multiple lipomas resembling benign symmetric lipomatosis were described in families with MERRF carrying the 8344A>G mutation in the tRNALys gene of mtDNA.

Methods: We show a extremely uncommon case with multisystem involvement and genetic confirmation.

Results: A 63-year-old woman,consulted for 5-year gait disorder and tremor in arms.Previous history:cervical lipoma (Madelung disease) diagnosed at 32-year-old,Wolf-Parkinson-White syndrome, sensorial polyneuropathy since 6 years, 4-year progressive night-time dyspnoea.Her mother and one sister had cervical lipomas.She told 10-year jerky movement in arms that improved with clonazepam.General exam:big cervical lipoma.Neurological findings were action tremor in upper limbs, with spontaneous and negative myoclonus in arms and axial myoclonus while walking,dorsal deviation of trunk with myophatic and ataxic gait.Thigh muscles atrophy with upper and lower girdle paresia. Laboratory test: creatin kinase 1056 U/L(33-211), lactate 2.2 mmol/L(0.5-2.2). Brain MRI:cortico-subcortical and cerebellar atrophy, electroencephalography ruled out epileptiform activity showing generalized dysrhythmia.Genetic test by minisequencing,PCR-RFLP-microfluidics and direct sequencing of mitochondrial DNA in blood and urine samples,identified the 8344A>G mutation in MTTK gene (MERRF phenotype) and 14484T>C mutation in MTND6 gen (Leber Hereditary Optic Neuropathy phenotype).

Conclusions: In our patient, the diagnosis of Madelung’s disease initially limited the diagnostic process delaying the identification of an underlying mitochondrial cytopathy.We suggest in patients with hereditary cervical lipomas and myoclonus performing a mitochondrial genetic test, searching the most common mutations.

Selected in Video-case presentations of MDS-ES Summer School, on 6th September 2015, in Prague, being awarded with the second prize.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/beyond-initial-clinical-phenotype-of-madelung-disease-myoclonus-gait-disorder-and-multisystem-involvement-led-to-genetic-diagnosis/