"Blepharophimosis-plus" syndromes: Frequency of systemic genetic disorders that also include blepharophimosis.

BACKGROUND: To determine the frequency of isolated blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) versus systemic genetic disorders in patients presenting with blepharophimosis. METHODS: Retrospective clinical records review. The records of all patients with blepharophimosis seen in the Division of Ophthalmology at the Children's Hospital of Philadelphia during a 12-year-period (2009-2020) were reviewed for medical history, clinical examination findings and results of genetic analyses. RESULTS: The 135 patients identified with blepharophimosis included 72 females (53%) and 63 males (47%) whose mean ± standard deviation age at first visit was 3.5 ± 6.4 years (range 0-39.8 years). Sixty-seven of the patients (50%) had undergone genetic testing for FOXL2 gene mutation. Fifty-four (81%) harboured FOXL2 gene mutations and 13 (19%) did not. Altogether, 126 patients (93%) had a final diagnosis of isolated BPES. The remaining nine (7%) had syndromic diagnoses ("blepharophimosis-plus"), including Dubowitz syndrome (n = 2), Ohdo syndrome (n = 1), 22q11.2 duplication (n = 1) and 3q22 deletion (n = 2). Three patients with multiple congenital anomalies remain undiagnosed. CONCLUSIONS: Blepharophimosis is an eyelid feature occurring most commonly in isolation due to FOXL2 gene mutation, but can also be a harbinger of multisystem disease not exclusive to isolated BPES, as observed in 7% of cases in this series. The ophthalmologist is often the first to recognise these unique features, and must consider and rule out non-BPES syndromes before establishing a diagnosed classic BPES. A comprehensive genetic evaluation is, therefore, indicated in all cases.

Ophthalmologic findings in Russian children with fetal alcohol syndrome.

PURPOSE: To study functional and anatomic characteristics of eyes of Russian children with fetal alcohol syndrome (FAS).
 METHODS: One hundred children aged 10-16 years from Russian orphanages (St. Petersburg) were examined: 50 with verified diagnosis of FAS and 50 healthy children. All children were tested for distance visual acuity (VA) with subjective optimal correction (Sivtsev chart), skiascopy, visual inspection for FAS external ocular features, biomicroscopy, eye alignment using cover test, and indirect ophthalmoscopy.
 RESULTS: All analyzed parameters were worse in children with FAS compared with controls. Children with FAS showed a higher incidence of amblyopia, hyperopia, astigmatism, and anisometropia. In children with FAS, the incidence of blepharophimosis was 34% (8% in controls), epicanthus 14% (2% in controls), telecanthus 32% (compared to 4% in controls), eyelid ptosis 9% (none in controls), and strabismus 26% (10% in controls). Ophthalmoscopy revealed a tilted optic disc in 5 children with FAS (7%) compared with none in controls.
 CONCLUSION: Russian children with FAS have a higher incidence of vision problems and eye pathology that needs to be taken into account and requires ophthalmologist monitoring.

Blepharophimosis-ptosis-epicanthus inversus syndrome in a Pakistani pedigree.

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a rare developmental ocular disorder. We report this condition affecting 4 members of a Pakistani family across three generations. A 2-year-old girl was brought to the clinic by her father for the correction of her shortened palpebral fissures. Examination findings were consistent with BPES. The girl's father, paternal grandfather and paternal aunt also had identical features. The distance between the medial canthi of the index case was 30 mm, and the lengths of vertical and horizontal palpebral fissure were 6 mm and 20 mm, respectively. BPES must be considered an important differential diagnosis in patients presenting with blepharoptosis and blepharophimosis.

A gene for blepharophimosis-ptosis-epicanthus inversus syndrome maps to chromosome 3q23.

Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is an autosomal dominant malformation of the eyelids that may severely impair visual function. Chromosomal aberrations involving chromosomes 3q23, 3p25 and 7p34 have been reported in BPES but the disease gene has not been hitherto localized by linkage analysis. We have mapped a gene for BPES to chromosome 3q23 in a large French pedigree (Zmax = 4.62 at Theta = 0 for probe AFM 182yc5 at locus D3S1549). The best estimate for the location of the disease gene is at locus D3S1549, between the loci D3S1292 and D3S1555 (maximum lod score of 5.10).