AP4S1 and Spastic paraplegia: In total, 27 patients from nine kindreds, including nine with AP4E1 mutations, nine with AP4B1 mutations, six with AP4S1 mutations, and three with AP4M1 mutations [4], [5], [6], [7], [8], have a uniform clinical phenotype of type I complex HSP, characterized by severe intellectual disability, microcephaly, progressive spastic paraplegia, growth retardation and a stereotypical laugh.