Abstract
Prevalence of intellectual disability (ID) varies from 1–3%. Genetic causes of ID
are being increasingly recognized. Although multiple mutations have been identified
as a cause of syndromic ID, the genetic etiology of non-syndromic ID is poorly understood.
However, more than 100 loci have been mapped that are associated with non-syndromic
ID. There have been a couple of reports of AP4B1 gene mutation causing severe intellectual disability, absent speech, shy character,
stereotypic laughter, muscular hypotonia that progressed to spastic paraplegia, microcephaly,
foot deformity, decreased muscle mass of the lower limbs, inability to walk, and growth
retardation. They had structural brain abnormalities and seizures. The reported cases
were from Arab families where consanguineous marriage is common. We encountered an
African-American child who presented first at the age of 24 mo with language difficulties
and was subsequently found to have moderate to severe intellectual disability by standardized
tests. Shortly, he started to have seizures and problems with ambulation. Although
he was hypotonic at the time of presentation, legs slowly became spastic at the age
of 4 yr. After a thorough work up, he was found to have heterozygous mutation in the AP4B1 gene along with another missense mutation in the same gene. There has been no report
of mutation in this gene in the North American population. Although AP4B1 typically is said to be an autosomal recessive disease-causing gene, our case is
different in the sense that there are two mutations in the same gene one of which
has never been reported before and co-exists with a known disease causing mutation.
Yet, the phenotype of the case closely resembles those published previously.
Keywords
Intellectual disability -
AP4B1
- hereditary spastic paraplegia
