Two cases of Vici syndrome associated with Idiopathic Thrombocytopenic Purpura (ITP) with a review of the literature

Huenerberg, Katherine; Hudspeth, Michelle; Bergmann, Shayla; Pai, Shashidhar; Singh, Balvir; Duong, Angie

doi:10.1002/ajmg.a.37589

Cited by 10 publications

(10 citation statements)

References 7 publications

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“…He also developed myopathy, elevated liver enzymes, and intractable seizures, which were previously proposed to be typical features in Vici syndrome. Moreover, he suffered from severe gastroesophageal reflux disease similarly to four previously reported patients for whom Nissen fundoplication or gastrostomy was necessitated (Balasubramaniam et al., ; Huenerberg et al., ; Shimada et al., ; Tasdemir et al., ). Gastroesophageal reflux disease may be therefore considered as part of the associated clinical spectrum.…”

Section: Resultssupporting

confidence: 56%

“…In addition to these phenotypic features, cardiomyopathy, developmental delay, microcephaly, and failure to thrive were described as typical consequences (Byrne et al., ; Chiyonobu et al., ; del Campo et al., ). Since the first description, more than 40 families have been published with Vici syndrome (VICIS), who were compatible with an autosomal recessive transmission and have extended the variable clinical spectrum with myopathy, epilepsy, elevated aminotransferases, thymus aplasia, thrombocytopenic purpura, sensorineural hearing loss, and renal tubular acidosis (Aggarwal, Tandon, Bhowmik, & Dalal, ; Al‐Owain et al., ; Alzahrani, Alghamdi, & Waggass, ; Balasubramaniam et al., ; Byrne et al., ; Chiyonobu et al., ; Cullup et al., ; del Campo et al., ; Demiral, Sen, Esener, Ceylaner, & Tekedereli, ; El‐Kersh, Jungbluth, Gringras, & Senthilvel, ; Hedberg‐Oldfors, Darin, & Oldfors, ; Hori et al., ; Huenerberg et al., ; Maillard et al., ; McClelland et al., ; Miyata et al., ; Ozkale, Erol, Gümüs, Ozkale, & Alehan, ; Rogers, Aufmuth, & Monesson, ; Said, Soler, & Sewry, ; Shimada et al., ; Waldrop et al., ). The prognosis was found to be poor with a median survival of 42 months (Byrne, Dionisi‐Vici, Smith, Gautel, & Jungbluth, ).…”

Section: Introductionmentioning

confidence: 99%

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EPG5 c.1007A > G mutation in a sibling pair with rapidly progressing Vici syndrome

Vojcek

Keszthelyi

Jávorszky

et al. 2019

Annals of Human Genetics

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We report on a sibling pair with the EPG5 c.1007A > G mutation who developed a severe form of Vici syndrome and died in infancy. The c.1007A > G (p.Gln336Arg) mutation, affecting the penultimate nucleotide and the splicing of exon 2 is the most common mutation of EPG5 and is typically associated with a less devastating prognosis: cardiomyopathy and cataract are less frequent consequences and the median survival time is 78 months compared to an overall median survival of 42 months. The less severe course related to c.1007A > G was formerly explained by the preserved canonical splicing in 25% of the transcripts. In contrast, we found the messenger RNA encoded by the c.1007A > G allele to be absent, explaining the severe course of the disease. This family provides another example of phenotypic variability related to a differential splicing. K E Y W O R D Sdifferential splicing, Gln336Arg, phenotype variability, Vici syndrome 80 wileyonlinelibrary.com/journal/ahg Ann Hum Genet. 2020;84:80-86.

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Section: Resultssupporting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

EPG5 c.1007A > G mutation in a sibling pair with rapidly progressing Vici syndrome

Vojcek

Keszthelyi

Jávorszky

et al. 2019

Annals of Human Genetics

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“…Vici syndrome [OMIM 242840] is a recessively inherited multisystem disorder, characterized by ACC, skin, hair, and retinal hypopigmentation, cataracts, acquired microcephaly, failure to thrive, cardiomyopathy, profound developmental delay, and combined immunodeficiency [Cullup et al, , ; Byrne et al, , ]. Since the original report, approximately 50 cases have been published [del Campo et al, ; Chiyonobu et al, ; Miyata et al, ; Al‐Owain et al, ; McClelland et al, ; Rogers et al, ; Finocchi et al, ; Ozkale et al, ; Said et al, ; Ehmke et al, ; El‐Kersh et al, ; Byrne et al, ; Ebrahimi‐Fakhari et al, ; Huenerberg et al, ; Tasdemir et al, ]. Additional signs are midline defects, that is cleft or palate thymic hypoplasia, hypospadia, facial dysmorphism, recurrent pulmonary infections, and renal tubular acidosis [Ebrahimi‐Fakhari et al, ].…”

Section: Discussionmentioning

confidence: 99%

Prenatal and postnatal presentations of corpus callosum agenesis with polymicrogyria caused by EGP5 mutation

Maillard

Cavallin

Piquand

et al. 2017

American J of Med Genetics Pt A

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EPG5-related Vici syndrome is a rare multisystem autosomal recessive disorder characterized by corpus callosum agenesis (ACC), hypopigmentation, cataracts, acquired microcephaly, failure to thrive, cardiomyopathy and profound developmental delay, and immunodeficiency. We report here the first case of prenatally diagnosed Vici syndrome with delayed gyration associated with ACC. Trio based exome sequencing allowed the identification of a compound heterozygous mutation in the EPG5 gene. Our patient subsequently demonstrated severe developmental delay, hypopigmentation, progressive microcephaly, and failure to thrive which led to suspicion of the diagnosis. Her MRI demonstrated ACC with frontoparietal polymicrogyria, severe hypomyelination, and pontocerebellar atrophy. This prenatal presentation of malformations of cortical development in combination with ACC expands the EPG5-related phenotypic spectrum. Our report supports the idea that EPG5-related Vici syndrome is both a neurodevelopmental and neurodegenerative disorder. © 2017 Wiley Periodicals, Inc.

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“…Additional variable multisystem involvement, not infrequently observed in individual patients, include sensorineu-ral hearing loss (McClelland et al 2010), unilateral lung hypoplasia (Al-Owain et al 2010), skeletal myopathy (Said et al 2012), mild dysmorphism with coarse facial features, full lips and macroglossia resembling those observed in lysosomal storage disorders (Cullup et al 2013;Byrne et al 2016a), congenital midline defects such as cleft lip or palate, thymic aplasia and/or hypospadias (Vici et al 1988), hydronephrosis, renal dysfunction and renal tubular acidosis (Miyata et al 2007;Byrne et al 2016a), thyroid agenesis and dysfunction (Cullup et al 2013) and idiopathic thrombocytopenic purpura (ITP) (Huenerberg et al 2016).…”

Section: Introductionmentioning

confidence: 99%

EPG5-Related Vici Syndrome: A Primary Defect of Autophagic Regulation with an Emerging Phenotype Overlapping with Mitochondrial Disorders

et al. 2017

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Vici syndrome is a rare, under-recognised, relentlessly progressive congenital multisystem disorder characterised by five principal features of callosal agenesis, cataracts, cardiomyopathy, combined immunodeficiency and oculocutaneous hypopigmentation. In addition, three equally consistent features (profound developmental delay, progressive failure to thrive and acquired microcephaly) are highly supportive of the diagnosis. Since its recognition as a distinct entity in 1988, an extended phenotype with sensorineural hearing loss, skeletal myopathy and variable involvement of virtually any organ system, including the lungs, thyroid, liver and kidneys, have been described.Autosomal recessive mutations in EPG5 encoding ectopic P-granules autophagy protein 5 (EPG5), a key autophagy regulator implicated in the formation of autolysosomes, were identified as the genetic cause of Vici syndrome. The eight key features outlined above are highly predictive of EPG5 involvement, with pathogenic EPG5 mutations identified in >90% of cases where six or more of these features are present. The manifestation of all eight features has a specificity of 97% and sensitivity of 89% for EPG5-related Vici syndrome. Nevertheless, substantial clinical overlap exists with other multisystem disorders, in particular congenital disorders of glycosylation and mitochondrial disorders. Clinical and pathological findings suggest Vici syndrome as a paradigm of congenital disorders of autophagy, a novel group of inherited neurometabolic conditions linking neurodevelopment and neurodegeneration due to primary autophagy defects.Here we describe the diagnostic odyssey in a 4-year-old boy whose clinical presentation with multisystem manifestations including skeletal myopathy mimicked a mitochondrial disorder. A genetic diagnosis of Vici syndrome was made through whole genome sequencing which identified compound heterozygous variants in EPG5. We also review the myopathic presentation and morphological characterisation of previously reported cases.

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Two cases of Vici syndrome associated with Idiopathic Thrombocytopenic Purpura (ITP) with a review of the literature

Cited by 10 publications

References 7 publications

EPG5 c.1007A > G mutation in a sibling pair with rapidly progressing Vici syndrome

EPG5 c.1007A > G mutation in a sibling pair with rapidly progressing Vici syndrome

Prenatal and postnatal presentations of corpus callosum agenesis with polymicrogyria caused by EGP5 mutation

EPG5-Related Vici Syndrome: A Primary Defect of Autophagic Regulation with an Emerging Phenotype Overlapping with Mitochondrial Disorders

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