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Vici syndrome

ORPHA1493
Synonym(s) Dionisi-Vici-Sabetta-Gambarara syndrome
Prevalence <1 / 1 000 000
Inheritance Autosomal recessive
Age of onset Antenatal
Neonatal
ICD-10
  • Q87.8
OMIM
UMLS
  • C1855772
MeSH -
MedDRA -

Summary

Vici syndrome is a very rare and severe congenital multisystem disorder characterized by the principal features of agenesis of the corpus callosum, cataracts, oculocutaneous hypopigmentation, cardiomyopathy and combined immunodeficiency.

Prevalence is unknown. Only 20 cases have been reported to date.

Vici syndrome is usually diagnosed in the first years of life. The phenotype is variable but the principal diagnostic features are almost always present at onset or evolve over time. Swallowing and feeding difficulties may be noted early on and may lead to failure to thrive. Cataracts are the most frequent ocular abnormality observed but others include optic nerve hypoplasia (see this term), nystagmus and photophobia. Hypopigmentation of eyes and hair is relative to the familial or ethnic background. Cardiomyopathy may evolve over time, leading to progressive heart failure. Most patients suffer from recurrent infections during infancy, often affecting the respiratory, gastrointestinal and urinary tracts, but can also include mucocutaneous candidiasis, conjunctivitis and sepsis. An associated skeletal muscle myopathy with hypotonia and motor developmental delay is common. Some patients can display facial dysmorphism (cleft lip/palate and micrognathia), or rarely, other dysmorphic features (i.e. syndactyly). Sensorineural hearing loss has been reported in some and is probably underdiagnosed. Other structural CNS abnormalities, psychomotor retardation and seizures may also be present. Thymus, thyroid, liver and kidney involvement, as well as hematological abnormalities, have been rarely reported. Death is mainly due to cardiac complications or severe infections.

Vici syndrome is due to mutations in the EPG5 gene (18q12.3) which encodes an important autophagy regulator, ectopic P-granules autophagy protein 5 (epg5). The autophagy pathway involves several tightly regulated steps, evolving from the initial formation of phagophores to autophagosomes, whose fusion with lysosomes results in the final structures of degradation, autolysosomes. Formation of autolysosomes is specifically disturbed by an epg5 deficiency.

Diagnosis is based mainly on the presence of the characteristic clinical features. Brain MRI visualizes agenesis of the corpus callosum and an ocular examination (slit lamp exam) can identify any cataracts or ocular abnormalities. Electrocardiogram (ECG) and cardiac ultrasound are useful in assessing cardiac function. Immunological studies are also performed. Molecular genetic testing, identifying mutations in the EPG5 gene, confirms diagnosis.

Differential diagnoses include Marinesco-Sjogren syndrome, Chédiak-Higashi syndrome, Griscelli syndrome, DiGeorge syndrome or ataxia-telegiectasia (see these terms).

Prenatal diagnosis is possible in families with a known disease causing mutation.

Inheritance is autosomal recessive and genetic counseling is possible.

Treatment of Vici syndrome is purely supportive. In patients with seizures, anticonvulsant therapy should be instituted. Tube feeding may be necessary in those with feeding difficulties. Intercurrent infections should receive prompt and aggressive antibiotic treatment. In those with severe immunodeficiency, intravenous immunoglobulin replacement and antimicrobial prophylaxis should be considered. Cardiac function should be monitored regularly and immediate medical treatment instituted in case of evolving cardiac failure. Cataracts can be surgically corrected and hearing aids can be provided as necessary. Thyroid, liver and kidney function should be regularly monitored.

The overall prognosis is poor but may improve if the condition is diagnosed early and if cardiac and immunological aspects of the disease are managed proactively.

Expert reviewer(s)

  • Dr Heinz JUNGBLUTH

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Detailed information

Guidance for genetic testing
  • EN (2013,pdf)
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