Blepharophimosis-ptosis-epicanthus inversus syndrome plus: deletion 3q22.3q23 in a patient with characteristic facial features and with genital anomalies, spastic diplegia, and speech delay.

Blepharophimosis-ptosis-epicanthus inversus syndrome(BPES; OMIM110100) is a genetic disorder usually inherited in an autosomal dominant manner. Primarily, its diagnosis is based on four major features present at birth: short horizontal palpebral fissures (blepharophimosis), drooping of the eyelids (ptosis), a vertical fold of skin from the lower eyelid up either side of the nose (epicanthus inversus), and lateral displacement of the inner canthi with normal interpupillary distance(telecanthus; Oley and Baraitser, 1988). Two types of BPES are recognized: type I BPES includes the four major eyelid features and female infertility as a result of premature ovarian failure, whereas type II BPES consists only of eyelid abnormalities (Zlotogora et al., 1983). BPES is sometimes associated with developmental delay, but patients with BPES typically have a normal lifespan (Oley and Baraitser, 1988; Beysen et al., 2009). The clinical diagnosis of BPES is confirmed with demonstration of a FOXL2 mutation, subtle FOXL2 deletion or 3q23 microdeletion, or deletion of the FOXL2 regulatory region (Crisponi et al., 2001; De Baere et al., 2003; Beysen et al., 2005; D’haene et al., 2009). FOXL2, located at 3q23, is the only gene currently known to be associated with BPES (Beysen et al., 2009). It is possible to identify an underlying genetic defect in 88% of BPES cases diagnosed clinically (Beysen et al., 2009). Of the genetic defects found, approximately 81% are intragenic mutations of FOXL2, 10–12% are microdeletions of the gene or surrounding areas, and 5% are deletions in the regulatory areas (Beysen et al., 2009; D’haene et al., 2009,2010). In BPES-like patients (i.e. those displaying some,but not all four major features of BPES), other copy number changes can be detected in 33% of cases(Gijsbers et al., 2008). Patients with BPES carrying larger deletions encompassing FOXL2 present more frequently with associated clinical findings, such as mental retardation (D’haene et al., 2009). In this study, we present a child with BPES caused by a large interstitial deletion,3q22.3q23 (chr3:139 354 104–144 013 999)(hg18), which includes FOXL2. In addition to the classic features of BPES, he presents with an external genital anomaly,spastic diplegia, and speech delay.