PURPOSE: To identify the mutation leading to syndromic choroideremia (CHM) in two families and to define fundus autofluorescence (FAF) in CHM carriers. METHODS: The ophthalmic and clinical phenotype was investigated including FAF, neuropediatric, otorhinolaryngologic, cardiologic, and nephrologic examinations of three male patients (age, 11-46 years) and three female carriers (age, 11-46 years) from two families. Genomic DNA amplification (PCR) of the REP1 gene as well as adjacent loci was used to determine the molecular basis of the phenotype. RESULTS: Analysis of genomic DNA revealed large deletions that asymmetrically flank REP1 in both families, ranging from a minimum size of 6.3 and 8.5 mega base pairs (Mbp) to a maximum size of 9.7 and 14.1 Mbp, respectively. In addition to CHM, patients from these families exhibited mild syndromic features, including mental and motor retardation and low-frequency hearing loss. FAF showed a distinctive pattern characterized by small areas of reduced and increased autofluorescence in all female carriers. CONCLUSIONS: Both CHM families are the first to be described with large deletions that manifest with a mild syndromic phenotype. The location of the deletions indicates that they may allow sublocalization of the syndromic features to the most proximal region of X-linked distal spinal muscular atrophy (DSMAX) and Martin-Probst deafness mental retardation syndrome (MPDMRS). The FAF pattern is specific to CHM carriers and thus will help to identify and differentiate between carriers of other X-linked recessive carrier states such as in X-linked retinitis pigmentosa.