Objectives To identify the phenotype, genetic defect and inheritance pattern of ectopia lentis et pupillae (ELP) in a large Dutch family, previously diagnosed as presumed autosomal dominant ELP because of the occurrence of ELP in three generations.

Design A clinical and genetic study of children and adults.

Participants Eight patients of the ELP family, including five new patients from the youngest generation.

Methods Standard ophthalmological examinations were performed. For molecular genetic analysis, the coding region of ADAMTSL4 was sequenced. Main outcome measures were the ocular phenotype of the new ELP patients, the inheritance pattern and the identification of mutations in the ADAMTSL4 gene in the family.

Results Of the eight patients with ectopia lentis, seven fulfilled the clinical diagnostic criteria of ELP. Molecular genetic analysis of these seven patients disclosed two novel mutations in the ADAMTSL4 gene: homozygous (p.Q752X/p.Q752X) in six patients and compound heterozygous (p.Q752X/p.Q758fs) in one patient. Heterozygosity in phenotypically normal parents proved autosomal recessive (AR) inheritance. The pseudodominant inheritance pattern can be explained by high carrier frequency in this small community and/or consanguinity.

Conclusions Patients from a family with ELP in four generations have AR ELP caused by novel mutations in ADAMTSL4. The clinical presentation of ELP can be variable, but all patients of our study with homozygous p.Q752X mutation have ectopia lentis and pupillary dysfunction in common.