Shawky, Rabah M.

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The Egyptian Journal of Medical Human Genetics 19 (2018) 49–50Contents lists available at ScienceDirectThe Egyptian Journal of Medical Human Geneticsjournal homepage: www.sciencedirect .comCardiomyopathy in Vici syndromehttps://doi.org/10.1016/j.ejmhg.2017.12.0031110-8630/ 2018 Production and hosting by Elsevier B.V. on behalf of Ain Shams University.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Peer review under responsibility of Ain Shams University.Dear Editor,A 7 month old boy was referred to our clinic with provisionaldiagnosis of Pompe disease because of his Echocardiographic find-ings of hypertrophic cardiomyopathy. Although the patient hadsevere hypotonia and increased CPK level characteristics of Pompedisease, other clinical findings made this diagnosis unlikely.Our patient is the 2nd in order of birth of first cousin parentsdelivered at full term by vaginal delivery after an uncomplicatedpregnancy. The main complaint of the patient was failure to thrive,recurrent chest infections that needed frequent hospital admis-sions and generalized hypotonia. During his last admission,Echocardiography was done and revealed hypertrophiccardiomyopathy.On examination, he had failure to thrive, his weight was 3.8 kg(below 3rd percentile), his length was 61 cm (below 3rd per-centile) and his skull circumference was 37 cm (below 3rd per-centile). The patient had oculocutaneous albinism, sparse scalphair, micrognathia and high arched palate. Neurologic examinationrevealed global developmental delay, generalized hypotonia,decreased deep tendon reflexes and preserved superficial reflexes.Sensations were intact. Abdominal examination was clinically nor-mal and he had normal male external genitalia. Family history wasunremarkable. Ophthalmology examination revealed foveal hypo-plasia, pale optic disc, bilateral ocular albinism and bilateral ante-rior polar cataract.Complete blood picture revealed anemia, persistent leucopeniaand normal platelets (Hgb: 9.5 g/dL, platelets 415,000/cm3, WBCs3.600/mm3, lymphocytes: 35%, neutrophils: 49% and monocytes14%). Total CPK level was 363 U/L (normal 25–130). Liver and Kid-ney function tests were normal.Extended metabolic screen, serum lactate, serum ammonia,organic acids in urine, plasma very long chain fatty acids, plasmaacid maltase enzyme revealed no abnormalities. EEG revealed focalright frontal – temporal epileptogenic dysfunction. MRI brainrevealed agenesis of corpus callosum (ACC), pontine hypoplasiaand infracerebellar arachnoid cyst (Fig. 1). Unfortunately, thepatient died with severe pneumonia before doing furtherinvestigations.Our patient was diagnosed as Vici syndrome based on the pres-ence of diagnostic clinical criteria including ACC, albinism, car-diomyopathy, immunodeficiency (leucopenia and neutropenia),cataracts, and skeletal myopathy [1]. The syndrome was firstdescribed in 1988, in two brothers with ACC, bilateral cataracts,cleft lip and palate, hypopigmentation of the skin and hair, com-bined immunodeficiency, and severe psychomotor retardation [2].Similar to patients with Pompe disease, Vici patients havehypotonia sometimes with elevated muscle enzymes suggestinga muscular origin. This was confirmed by muscle biopsy in ninepatients [3]. Vici patients may also have cardiomyopathy whichusually develops early in life but sometimes its onset is delayed tillchildhood. Both hypertrophic and dilated forms were reported[4,5]. Our patient had early onset hypertrophic type ofcardiomyopathy.He also had recurrent respiratory infection which is one of themajor symptoms of Vici syndrome which can be explained by car-diomyopathy, hypotonia and variable range of immunodeficiency[6].One of the differentiating features of Vici syndrome is the CNSanomalies which is absent in Pompe disease. This includes ACC,cerebellar vermal hypoplasia, polymicrogyria/abnormal gyration,cerebral atrophy/hypoplasia, absent septum pellucidum, and hypo-plasia of the pons. Our patient had agenesis of corpus callosum,pontine hypoplasia and infra-cerebellar arachnoid cyst [5].Another differentiating feature is the ocular features whichincludes cataract, optic nerve hypoplasia, visual impairment andfundus hypopigmentation [3,7]. Our patient had foveal hypoplasia,pale optic disc, bilateral ocular albinism and bilateral anterior polarcataract.A cardinal feature is the marked oculocutaneous hypopigmen-tation relative to the familial and ethnic background. Children withVici syndrome have generally pale skin with light (often veryblonde in those of Caucasian origin as detected in our patient) hair,rather than discrete hypopigmented patches [8].The diagnosis of Vici syndrome is confirmed by finding recessivemutations in the EPG5 gene located at chromosome 18q12.3 andencoding the key autophagy regulator: Ectopic P-Granules protein5. Autophagy is a fundamental cellular degradative pathway withimportant roles in the removal of defective proteins and organelles,defense against infections and adaptation to changing metabolicdemands [9]. This is done through several steps started by the for-mation of isolatedmembranes (phagophores) then fusionwith lyso-somes (autophagosome) and finally the degradation step(autolysosome) [10]. There is currently no cure for Vici syndromeand management is essentially supportive, aimed at alleviating theeffects of extensive multisystem involvement [11].To conclude, cardiomyopathy is a key sign of Vici syndrome butit should not be confused with Pompe disease because of the neu-rodevelopmental delay, CNS anomalies and characteristic albinism.Fig. 1. MRI brain showing pontine hypoplasia and infracrebellar arachnoid cyst.50 Letters to the Editor / The Egyptian Journal of Medical Human Genetics 19 (2018) 49–50References[1] Cullup T, Dionisi-Vici C, Kho AL, Yau S, Mohammed S, Gautel M, et al. Clinicalutility gene card for: Vici syndrome. Eur J Hum Genet 2014;22:e1–4.[2] Vici CD, Sabetta G, Gambarara M, et al. Agenesis of the corpus callosum,combined immunodeficiency, bilateral cataract, and hypopigmentation in twobrothers. Am J Med Genet 1988;29:1–8. no. 1.[3] Ehmke N, Parvaneh N, Krawitz P, Ashrafi M-R, Karimi P, Mehdizadeh M, et al.First description of a patient with Vici syndrome due to a mutation affectingthe penultimate exon of EPG5 and review of the literature. Am J Med GenetPart A 2014;164A:3170–5.[4] Miyata R, Hayashi M, Itoh E. Pathological changes in cardiac muscle andcerebellar cortex in Vici syndrome. Am J Med Genet A 2014;164A(12):3203–5.[5] Rogers CR, Aufmuth B, Monesson S: Vici syndrome: a rare autosomal recessivesyndrome with brain anomalies, cardiomyopathy, and severe intellectualdisability. Case Reports in Genetics 2011, Volume 2011.[6] Finocchi A, Angelino G, Cantarutti N, Corbari M, Bevivino E, Cascioli S, et al.Immunodeficiency in Vici syndrome: A heterogeneous phenotype. Am J MedGenet Part A 2012;158A:434–9.[7] Filloux FM, Hoffman RO, Viskochil DH, Jungbluth H, Creel DJ. Ophthalmologicfeatures of Vici syndrome. J Pediatr Ophthalmol Strabismus 2014;51(4):214–20.[8] Byrne S, Jansen L, U-King-Im JM, Siddiqui A, Lidov HG, Bodi I, et al. EPG-relatedVici syndrome: a paradigm of neurodevelopmental disorders with defectiveautophagy. Brain 2016;139:765–81.[9] Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, et al.Guidelines for the use and interpretation of assays for monitoring autophagy.Autophagy 2012;8(4):445–544.[10] Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues. Cell2011;147(4):728–41.[11] Byrne S, Dionisi-Vici C, Smith L, Gautel M, Jungbluth H. Vici syndrome: areview. Orphan J Rare Dis 2016;11:21.Solaf M. Elsayed⇑Radwa GamalGenetics Unit, Children’s Hospital, Ain Shams University, Egypt⇑ Corresponding author at: Medical Genetics Center. 27 A BaghdadSt., Korba, Cairo, Egypt.E-mail addresses: elsayed683@yahoo.com,elsayed683@med.asu.edu.eg (S.M. Elsayed)Available online 12 January 2018

Cardiomyopathy in Vici syndrome

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Cardiomyopathy in Vici syndrome

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