Two sisters from a consanguineous couple were seen in genetics department for facial dysmorphic features and glaucoma. They both had broad foreheads, hypertelorism, megalocorneas, thick eyebrows with synophrys, flat malar regions, broad and bulbous noses, and mild prognathism. Both had glaucoma, younger one also had cataracts and phthisis bulbi. Other findings included bilateral partial cutaneous syndactyly of 2nd and 3rd fingers, history of impacted teeth with dentigerous cyst in the elder one, and intellectual disability (mild and borderline). The sisters were considered to have Elsahy-Waters syndrome. In order to elucidate the underlying molecular cause, sisters and their healthy parents were genotyped by SNP arrays, followed by homozygosity mapping. Homozygous regions were further analyzed by exome sequencing in one affected individual. A homozygous indel variant segregating with the condition was detected in CDH11 (c.1116_1117delinsGATCATCAG, p.(Ile372MetfsTer9)), which was then validated by using Sanger sequencing. CDH11 encodes cadherin 11 (osteo-cadherin) that regulates cell-cell adhesion, cell polarization and migration, as well as osteogenic differentiation. Further experiments revealed that CDH11 expression was decreased in patient-derived fibroblasts as compared to the heterozygous parent and another healthy donor. Immunostaining showed absence of the protein expression in patient fibroblasts. In addition, cell proliferation rate was slow and osteogenic differentiation potential was delayed. We consider that this study reveals loss-of-function mutations in CDH11 as a probable cause of this phenotype. Next generation sequencing in further patients would both prove this gene as causative, and finely delineate this clinical spectrum further contributing in identification of other possibly involved gene(s).

Erkan-Turan K, Taylan-Şekeroğlu H, Ağın A, Sanaç AŞ. Why and when to prefer botulinum toxin injection in childhood strabismus? Turk J Pediatr 2017; 59: 684-687. The aim of this study was to investigate the indications and outcomes of botulinum toxin injection in children with strabismus. The medical records of children who underwent botulinum toxin injection were reviewed. Eighteen patients (13 boys, 5 girls) with a mean age of 9.08±5.93 (6 months to 17 years) years were enrolled in the study. The main indication and diagnosis, initial and final deviation at primary position and the presence of abnormal head position were all evaluated. The most common diagnosis was sixth nerve palsy (7 patients) followed by Duane`s syndrome (4 patients), acquired esotropia (2 patients), acquired exotropia (2 patients), consecutive exotropia (2 patients) and sensory strabismus (1 patient). The leading indications for botulinum toxin injections were the presence of abnormal head position, diplopia and ocular misalignment at primary position. All patients received monocular injection. Fourteen patients had one, 4 patients had more than one injection. The mean follow-up period was 2.78±0.94 months for the first post-injection visit and 21.64±15.23 months for the last visit. Five patients underwent strabismus surgery due to inadequate response to injection. No complication related to injection was observed. Botulinum toxin injection may be preferred in pediatric age group particularly in case of extraocular muscle palsy, diplopia and concomitant deviation either to provide ocular alignment prior to surgery or to prevent the detrimental effect of diplopia on binocularity. The intervention seems to be safe and repeatable in children even though surgery is still inevitable in particular cases.