OMIM ID:
Vici Syndrome
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Congenital cataracts, both unilateral and bilateral are common. The fundus appears hypopigmented. Nystagmus, optic neuropathy, and mild ptosis have been reported. Nothing is known regarding acuity.
Systemic Features
Infants at birth have striking hypotonia with a weak cry and feeding difficulties. Dysmorphic features such as micrognathia, microcephaly, low-set ears, some degree of generalized hypopigmentation (hair and skin), and a broad nose with a long philtrum may be present. The face may appear triangular. Cleft lip and palate may be present. Evidence of cardiac dysfunction may also be present early with both dilated and hypertrophic cardiomyopathy reported. Hearing loss has been reported in some individuals. Recurrent infections are common and immunologic studies have revealed, in some patients, granulocytopenia, low T cell counts (primarily T4+ cells), thymic dysplasia, and low levels of IgG. Seizures may occur. Liver dysfunction has been variably reported.
Neurological and brain evaluations have reported agenesis of the corpus callosum, defects in the septum pellucidum, and hypoplasia of the cerebellar vermis along with pontocerebellar hypoplasia. Psychomotor retardation is severe in most individuals along with general growth retardation.
Histologic studies of skeletal muscle fibers have shown considerable variation in fiber size, centralized nuclei, fucsinophilic inclusions, and enlarged abnormal mitochondria. Other central nervous system abnormalities include in some individuals a paucity of white matter, schizencephaly, neuronal heterotopias, and enlargement of the ventricles.
The cumulative effects of these multiorgan abnormalities lead to death within the first year or two of life, generally of heart failure or sepsis.
Genetics
Inheritance
Homozygous or compound heterozygous mutations in the EPG5 gene (18q12.3) have been associated with this condition.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.