Linkage analysis identifies an isolated strabismus locus at 14q12 overlapping with FOXG1 syndrome region.

Strabismus is a common condition, affecting 1%-4% of individuals. Isolated strabismus has been studied in families with Mendelian inheritance patterns. Despite the identification of multiple loci via linkage analyses, no specific genes have been identified from these studies. The current study is based on a seven-generation family with isolated strabismus inherited in an autosomal dominant manner. A total of 13 individuals from a common ancestor have been included for linkage analysis. Among these, nine are affected and four are unaffected. A single linkage signal has been identified at an 8.5 Mb region of chromosome 14q12 with a multipoint LOD (logarithm of the odds) score of 4.69. Disruption of this locus is known to cause FOXG1 syndrome (or congenital Rett syndrome; OMIM #613454 and *164874), in which 84% of affected individuals present with strabismus. With the incorporation of next-generation sequencing and in-depth bioinformatic analyses, a 4 bp non-coding deletion was prioritised as the top candidate for the observed strabismus phenotype. The deletion is predicted to disrupt regulation of FOXG1, which encodes a transcription factor of the Forkhead family. Suggestive of an autoregulation effect, the disrupted sequence matches the consensus FOXG1 and Forkhead family transcription factor binding site and has been observed in previous ChIP-seq studies to be bound by Foxg1 in early mouse brain development. Future study of this specific deletion may shed light on the regulation of FOXG1 expression and may enhance our understanding of the mechanisms contributing to strabismus and FOXG1 syndrome.

Blau syndrome following a bacterial infection.

An 11-month-old girl presented with dermatitis, boggy arthritis, and keratitis shortly after her hospitalization for bacterial pneumonia. A skin biopsy and genetic testing led to a diagnosis of Blau syndrome. Her symptoms persisted despite a stepwise increase in immune-modulating therapies. Her ocular findings advanced to include bilateral panuveitis, optic disk edema, and hypopigmented chorioretinitis. We speculate that the bacterial infection triggered an inflammatory reaction throughout her body that was facilitated by the pathogenic NOD2 variant.

Long-term results of botulinum toxin-augmented medial rectus recessions for large-angle infantile esotropia.

PURPOSE: To evaluate the long-term results of medial rectus recessions augmented by botulinum toxin injection for treating infants with large-angle (> 60 prism diopters [PD]) infantile esotropia. DESIGN: Interventional case series. SETTINGS: Hospital-based clinical practice. PATIENT POPULATION: Twenty-three patients with large-angle infantile esotropia who were followed for at least 2 years postoperatively. INTERVENTION: Surgical treatment with botulinum toxin in addition to bilateral medial rectus muscle recessions. The preoperative findings, treatment, and outcomes were reviewed. MAIN OUTCOME MEASURES: Surgery was considered successful if the patients did not require additional horizontal strabismus surgery and had less than 10 PD of horizontal deviation. RESULTS: The age at surgery ranged from 4 to 36 months (mean 14.5 months) and the angle of esotropia ranged from 65 to 100 PD (mean 72 PD). Treatment was successful in 17 of 23 patients (74%), with follow-up of 2 to 13 years (mean 6.6 years). CONCLUSION: Botulinum toxin-augmented medial rectus recession is an effective treatment for large-angle infantile esotropia, with stable results over time.

Congenital orbital fibrosis: a distinct clinical entity.

PURPOSE: To describe congenital orbital fibrosis as a distinct clinical entity, and highlight its constellation of features. MATERIAL AND METHODS: Retrospective, noncomparative, interventional case series of 4 patients with congenital orbital fibrosis. One patient underwent exploration of the orbit, release and biopsy of scar tissue. Two patients underwent strabismus surgery. One of these also underwent upper eyelid lengthening. Blepharoptosis, eyelid retraction, enophthalmos, proptosis, presence of a diffusely infiltrating orbital mass with secondary involvement of extraocular muscles, and dysplasia of the affected bony orbit were identified. RESULTS: One patient presented with eyelid retraction, 1 with ptosis, and the remaining 2 had normal eyelid height. Furthermore, one patient demonstrated true enophthalmos. Of the remaining 3, 1 had symmetrical exophthalmometry, and 2 presented with proptosis. The later 2 patients presented with ipsilateral facial hypoplasia, accompanying orbital wall dysplasia and decreased orbital volume, confirmed on computed tomography. In addition, all patients demonstrated an irregular, retrobulbar mass located medially within the orbit, incorporating the medial rectus muscle. CONCLUSION: Congenital orbital fibrosis is a nonfamilial, nonprogressive, unilateral, distinct clinical entity, characterized by the presence of a diffusely infiltrating orbital mass with secondary involvement of extraocular muscles resulting in variable symptomatology due to the cicatricial process.