A Saudi Infant with Vici Syndrome: Case Report and Literature Review

Abstract

INTRODUCTION:Vici syndrome, a rare autosomal recessive disorder, was first described in 1988 by Vici et al. Only 78 cases have been reported to date. The syndrome is characterised by agenesis of the corpus callosum, hypopigmentation, cardiomyopathy, progressive failure to thrive, dysmorphic features, immunodeficiency and cataracts. Mutations in the gene epg5 have been identified as the cause of Vici syndrome.CASE DESCRIPTION:The parents are a consanguineous Saudi couple with two other children diagnosed with Gaucher disease. The patient was born at term and in the first 5 months had many hospital admissions for a recurrent chest infection. Physical examination, investigations and imaging studies revealed that the patient had agenesis of the corpus callosum, cataracts, psychomotor delay, immunodeficiency and hypopigmentation. The initial echocardiogram was normal. At 7 months, genetic testing confirmed the diagnosis of Vici syndrome with a c.3693G>Ap (Gln1231Gln) mutation in the gene EPG5. The patient developed a chest infection and was admitted to the pediatric intensive care unit. An echocardiogram was repeated and showed significant left ventricular dilation with a Z-score of 3.1, moderate mitral and tricuspid regurgitation, and depressed ventricular function with a fractional shortening of 17% and ejection fraction 37%. The patient’s condition deteriorated, and he died aged 8 months.CONCLUSION:The symptoms of extensive system involvement in Vici syndrome have been present in the majority of reported cases and should prompt careful evaluation of this syndrome when such symptoms are present in an infant. In confirmed cases, close monitoring of the immune status and cardiac function, the two main causes of death among Vici syndrome patients, is vital to prevent rapid deterioration and improve life expectancy.

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

“…Intractable diarrhea developed in the female patient and was suggested to be secondary to malabsorption. This consequence is supposed to be linked to EPG5 ‐related autophagy depletion (Alzahrani et al., ; Hedberg‐Oldfors et al., ; Huenerberg et al., ; Shimada et al., ).…”

“…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, ).…”

The first Chinese case of Vici syndrome with novel compound heterozygous sequence variants in EPG5

“…Miyata et al (2007) also recorded two sibling patients suffering from VICIS, but the elder sister died at the age of 12 months because of heart failure. In 2018, Alzahrani and his colleges described a Saudi male infant affected by VICIS and died at the age of 8 months (Alzahrani et al, 2018). In the same year, Demiral et al reported a Turkish male patient died of VICIS due to sepsis at 1 year and 9 months old (Demiral et al, 2018).…”

Vici syndrome in Israel: Clinical and molecular insights

“…The condition was first described by the Italian physician Carlo Dionisi-Vici and colleagues in 1988, in two Italian brothers who died at 2 and 3 years of age due to bronchopneumonia. Since then, less than a hundred cases have been described worldwide, with a global prevalence of less than 1/1,000,000 ( Alzahrani et al, 2018 ).…”