Focus on progressive myoclonic epilepsy in Berardinelli-Seip syndrome
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LETTER TO THE EDITOR
Focus on progressive myoclonic epilepsy in Berardinelli-Seip syndrome Sofía Sánchez-Iglesias 1 & Antía Fernández-Pombo 1 & David Araújo-Vilar 1 Received: 15 June 2020 / Accepted: 26 September 2020 # Fondazione Società Italiana di Neurologia 2020
We have read the report of congenital generalized lipodystrophy (CGL) type 2 by Ferranti et al. [1] with interest. The authors report the case of two sisters with progressive myoclonic epilepsy (PME) associated to type 2 CGL due to the biallelic variant c.1048C>T (rs763070770, NM_001122955.3: p.Arg350Ter) in exon 8 of the BSCL2 gene. Apparently both patients presented an overlapping clinical phenotype suggestive of Berardinelli-Seip syndrome and progressive myoclonic epilepsy. The older sister died at the age of 18 due to the neurodegenerative nature of this disease. Strikingly, and despite the title of the report and a comment in the Abstract, the authors do not speak at all of lipodystrophy in the description of the cases, focusing mainly on the neurological features. Therefore, in addition to the lipodystrophic phenotype, it would have been essential for the authors to complete the clinical descriptions indicating if the patients presented acanthosis nigricans, hypertriglyceridemia, hepatomegaly, or phlebomegaly, and if so, from what age. We might hypothesize that the patients exhibited generalized lipoatrophy, but if this were not the case, it would suggest that the variant c.1048C>T does not impair the lipid droplet biogenesis. Except for the progression rate of the disease, the clinical features described by the authors are superimposable to those we reported years ago in the case of PELD (Progressive Encephalopathy with or without Lipodystrophy or Celia’s Encephalopathy, MIM: #615924) [2], caused by the variant c.985C>T in BSCL2. The PELD variant (rs587777606, NM_001122955.3: c.985C>T, p.(Arg329Ter) produces a cryptic splicing site, causing skipping of exon 7 in BSCL2, and giving rise to the truncated seipin p.(Tyr289Leufs*64). This leads to much higher brain expression of the shortest
* David Araújo-Vilar [email protected] 1
UETeM, CIMUS-IDIS, School of Medicine, University of Santiago de Compostela, Avda Barcelona s/n, 15782 Santiago de Compostela, Spain
BSCL2-201 transcript (which is hardly expressed in a normal brain, < 1%) [2] and which is harmful to neurons in homozygosity or compound heterozygosity [3]. PELD is an extremely rare neurodegenerative childhood disease with a fatal prognosis before the age of 9. Most, but not all, affected patients exhibit some signs of lipodystrophy (which is actually variable in homozygous PELD, with no acanthosis nigricans or muscular hypertrophy). The children who eventually died had developed progressive encephalopathy with psychomotor regression, cognitive deterioration, spasticity, loss of speech, and seizures between the ages of 2 and 3 [2]. In 2016, Opri et al. [4] described 3 patients with PME and recessively inherited CGL type 2 associated with known seipin variants. However, we have recently
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