Adult‐onset rapidly worsening progressive myoclonic epilepsy caused by a novel variant in DHDDS

Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T>C

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp.2008.157354 ◽

2009 ◽

Vol 81 (1) ◽

pp. 90-93 ◽

Cited By ~ 23

Author(s):

B Dermaut ◽

S Seneca ◽

L Dom ◽

K Smets ◽

L Ceulemans ◽

...

Keyword(s):

Leigh Syndrome ◽

Myoclonic Epilepsy ◽

Adult Onset ◽

Progressive Myoclonic Epilepsy

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Progressive myoclonic epilepsy due to rare mitochondrial ND6 mutation, m.14487T>C

BMJ Neurology Open ◽

10.1136/bmjno-2021-000180 ◽

2021 ◽

Vol 3 (1) ◽

pp. e000180

Author(s):

Anthony Khoo ◽

Saadnah Naidu ◽

Surapi Bhairavi Wijayendran ◽

Ashirwad Merve ◽

Fion Bremner ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Mitochondrial Disease ◽

Mitochondrial Gene ◽

Myoclonic Epilepsy ◽

Whole Genome ◽

Drug Resistant ◽

Adult Onset ◽

Cortical Myoclonus ◽

Progressive Myoclonic Epilepsy

IntroductionMitochondrial diseases exhibit wide phenotypic heterogeneity, and can present as progressive myoclonic epilepsy.SummaryWe report a case of adult-onset drug-resistant epilepsy, cortical myoclonus and bilateral optic neuropathies due to m.14487T>C, a rare mitochondrial gene mutation identified on whole-genome sequencing. This mutation, which affects the NADH dehydrogenase 6 (ND6) subunit of the mitochondrial respiratory chain, is most commonly implicated in cases of infantile-onset Leigh syndrome, although a broader phenotypic spectrum including migraine with aura and progressive myoclonic epilepsy have been described. Serial MRI scans over a 2-year period demonstrated the interval development of bihemispheric stroke-like lesions. Giant somatosensory evoked potentials and short-duration myoclonic jerks with craniocaudal spread on surface electromyography were consistent with cortical myoclonus. Optical coherence tomography showed bilateral symmetric thinning of the nerve fibre layer in the papillomacular bundles.ConclusionWhole-genome sequencing can help to provide a definitive diagnosis for mitochondrial disease and should be considered in situations where clinical suspicion remains high despite normal genetic panels or muscle histopathology. Mitochondrial disease can present as adult-onset progressive myoclonic epilepsy, and bilateral optic neuropathies can be a striking feature of ND6 mitochondrial gene mutations. In our case, severe cortical myoclonus affecting speech and swallowing remained highly drug-resistant, however, symptomatic benefit was derived from targeted onabotulinum toxin A injections.

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Transient neonatal diabetes due to a disease causing novel variant in the ATP-binding cassette subfamily C member 8 (ABCC8) gene unmasks maturity-onset diabetes of the young (MODY) diabetes cases within a family

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2020-0462 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Eleni Z Giannopoulou ◽

Olga Ovcarov ◽

Elisa De Franco ◽

Fabian Kassberger ◽

Susanne Nusser ◽

...

Keyword(s):

Autoimmune Diabetes ◽

Family Members ◽

Neonatal Diabetes ◽

Atp Binding ◽

Adult Onset ◽

Family History Of Diabetes ◽

Abcc8 Gene ◽

Onset Diabetes ◽

Novel Variant ◽

Atp Binding Cassette

AbstractObjectivesNeonatal diabetes mellitus (NDM) is a rare monogenic diabetes form, occurring mainly from ATP-binding cassette subfamily C member 8 (ABCC8) and KCNJ11 mutations. ABCC8 mutations have also been found to cause adult-onset diabetes. What is new?: •Novel ABCC8 mutation in an NDM case •Heterogeneous clinical presentation of diabetes and response to sulfonylurea therapy among family members with the same ABCC8 mutation.Case presentationWe report the case of a newborn with NDM and a heterozygous ABCC8 novel variant (c.3835G>A), successfully treated with sulfonylurea. The same ABCC8 variant was found in two other family members, already treated for type 2 diabetes.ConclusionsThis case demonstrates the variable phenotypic presentation of diabetes due to a novel ABCC8 mutation (c.3835G>A), ranging from transient NDM to adult-onset, insulin-demanding diabetes, among family members. Genetic testing in young individuals with a strong family history of diabetes, presenting with non-autoimmune diabetes is recommended as it can determine prognosis and treatment of affected family members.

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