Linkage analysis in blepharophimosis-ptosis syndrome confirms localisation to 3q21-24.

Blepharophimosis-ptosis is an autosomal dominant disorder in which previous chromosome rearrangements have suggested a putative gene location on the long arm ofchromosome 3. This paper confirms the location at 3q21-24 with linkage studies in two large families. A lod score of 3-2 was found with D3S1237. (JMed Genet 1995;32:774-777) The blepharophimosis-ptosis syndrome (BPES) was first described in 1841 by Fredrich August von Ammon.' It consists of blepharophimosis, ptosis, epicanthus inversus and some extraocular features such as learning difficulties and female infertility. The term blepharophimosis describes the reduction in the horizontal diameter of the palpebral fissure. This is associated with dysplasia of the eyelid owing to fibrosis and impairment ofthe laevator palpebrae superioris muscle.2 There may also be amblyopia and blockage of the lacrimal puncta.' Surgical correction is available to improve the cosmetic appearance of the eyes. Mild psychomotor retardation has been observed in some patients with one report giving a mean IQ score of 86.4 However most affected subjects have no significant learning difficulties. Infertility has been reported frequently in females but not in affected males. It has been suggested that there may be two subtypes depending on whether female infertility is present or not.5 The condition is an autosomal dominant trait. In 1991 Fukushima et alt published a case report of blepharophimosis sequence associated with a de novo balanced translocation 46,XY,t(3;4) (q23;p 15.2) and suggested that the locus might be assigned to 3q23. Following this Jewett et al7 reported a further case associated with an interstitial deletion at 3q22.7 The aim of our study was to confirm the putative location by linkage studies using two large families with BPES. Materials and methods The families were contacted and a full history and examination carried out on each member of the families. Inner canthal, outer canthal, and interpupillary distances were measured