Novel BRPF1 mutation in a boy with intellectual disability, coloboma, facial nerve palsy and hypoplasia of the corpus callosum.

Mutations in the chromatin regulator gene BRPF1 were recently associated with the Intellectual Developmental Disorder With Dysmorphic Facies And Ptosis (IDDDFP). Up till now, clinical data of 22 patients are reported. Besides intellectual disability (ID), ptosis and blepharophimosis are frequent findings, with refraction problems, amblyopia and strabism as other reported ophthalmological features. Animal studies indicate BRPF1 as an important mediator in brain development. However, only 5 of 22 previously reported patients show structural brain abnormalities. We report on an additional patient harboring a novel de novo nonsense mutation p.(Glu219*) in BRPF1. He presented with ID, bilateral iris colobomas, facial nerve palsy and severe hypoplasia of the corpus callosum. Our findings support previous findings of brain abnormalities in BRPF1-mutations and indicates coloboma and facial nerve palsy as possible additional features of IDDDFP syndrome.

Pediatric bag-in-the-lens intraocular lens implantation: long-term follow-up.

PURPOSE: To evaluate long-term follow-up results of pediatric cataract surgery using the bag-in-the-lens (BIL) intraocular lens (IOL) implantation technique. SETTING: Antwerp University Hospital, Edegem, Antwerp, Belgium. DESIGN: Prospective case series. METHODS: All pediatric cataract surgeries with BIL IOL implantation performed at the Antwerp University Hospital were evaluated. Only cases that completed a follow-up of 5 years at the hospital's Department of Ophthalmology were included in this study. RESULTS: Forty-six eyes of 31 children had a complete follow-up of 5 years or more after BIL IOL implantation. Sixteen cases were unilateral and 15 were bilateral. Patient age at time of surgery ranged from 2 months to 14 years. The mean refraction at the end of follow-up was -1.99 diopters (D) ± 3.70 (SD). In bilateral cases, a corrected distance visual acuity (CDVA) of better than 0.5 was attained in 86.7% and a CDVA of 1.0 was achieved in 56.7%. In unilateral cases, 31.2% achieved a CDVA of better than 0.5 but none obtained a CDVA of 1.0. A clear visual axis was maintained in 91.3% of cases during follow-up. Visual axis reopacification was detected in 4 eyes of 3 cases, all due to inadequate BIL IOL positioning. None of these eyes needed more than 1 intervention to maintain visual axis clarity. Other than 1 case of glaucoma, no severe complications were detected. CONCLUSION: Long-term follow-up results show that BIL IOL implantation is a safe, well-tolerated approach for treating pediatric cataract with a very low rate of visual axis reopacification and a low rate of secondary interventions for other postoperative complications. FINANCIAL DISCLOSURE: Dr. Tassignon has intellectual property rights to the bag-in-the-lens intraocular lens (U.S. patent 6 027 531; EU patent 009406794.PCT/120268), which is licensed to Morcher GmbH, Stuttgart, Germany. No other author has a financial or proprietary interest in any material or method mentioned.

Posterior capsule management in congenital cataract surgery.

UNLABELLED: Management of the posterior capsule significantly affects the outcome of pediatric cataract surgery. Posterior capsule opacification (PCO) is rapid and virtually inevitable in very young children when adult-style cataract surgery is performed and the posterior capsule is left intact. In eyes with pediatric cataract, primary posterior capsulotomy and vitrectomy are considered routine surgical steps, especially in younger children. The site of intraocular lens (IOL) fixation and the surgical technique used also affect the prevalence of PCO. The present systematic review evaluates the options available to prevent PCO or ensure a clear central visual axis after pediatric cataract surgery. Newer approaches to posterior capsule management such as pars plicata posterior capsulorhexis, sutureless vitrectomy, sealed-capsule irrigation, and bag-in-the-lens IOL are discussed. Management of the posterior capsule in the presence of a preexisting posterior capsule defect and posterior capsule plaque and options to treat PCO are also reviewed. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Phenotypic spectrum of dynamin 2 mutations in Charcot-Marie-Tooth neuropathy.

Dominant intermediate Charcot-Marie-Tooth neuropathy type B is caused by mutations in dynamin 2. We studied the clinical, haematological, electrophysiological and sural nerve biopsy findings in 34 patients belonging to six unrelated dominant intermediate Charcot-Marie-Tooth neuropathy type B families in whom a dynamin 2 mutation had been identified: Gly358Arg (Spain); Asp551_Glu553del; Lys550fs (North America); Lys558del (Belgium); Lys558Glu (Australia, the Netherlands) and Thr855_Ile856del (Belgium). The Gly358Arg and Thr855_Ile856del mutations were novel, and in contrast to the other Charcot-Marie-Tooth-related mutations in dynamin 2, which are all located in the pleckstrin homology domain, they were situated in the middle domain and proline-rich domain of dynamin 2, respectively. We report the first disease-causing mutation in the proline-rich domain of dynamin 2. Patients with a dynamin 2 mutation presented with a classical Charcot-Marie-Tooth phenotype, which was mild to moderately severe since only 3% of the patients were wheelchair-bound. The mean age at onset was 16 years with a large variability ranging from 2 to 50 years. Interestingly, in the Australian and Belgian families, which carry two different mutations affecting the same amino acid (Lys558), Charcot-Marie-Tooth cosegregated with neutropaenia. In addition, early onset cataracts were observed in one of the Charcot-Marie-Tooth families. Our electrophysiological data indicate intermediate or axonal motor median nerve conduction velocities (NCV) ranging from 26 m/s to normal values in four families, and less pronounced reduction of motor median NCV (41-46 m/s) with normal amplitudes in two families. Sural nerve biopsy in a Dutch patient with Lys558Glu mutation showed diffuse loss of large myelinated fibres, presence of many clusters of regenerating myelinated axons and fibres with focal myelin thickenings--findings very similar to those previously reported in the Australian family. We conclude that dynamin 2 mutations should be screened in the autosomal dominant Charcot-Marie-Tooth neuropathy families with intermediate or axonal NCV, and in patients with a classical mild to moderately severe Charcot-Marie-Tooth phenotype, especially when Charcot-Marie-Tooth is associated with neutropaenia or cataracts.

Bag-in-the-lens intraocular lens implantation in the pediatric eye.

PURPOSE: To study the efficacy, safety, and feasibility of implantation of a bag-in-the-lens intraocular lens (IOL) in children and babies. SETTING: Departments of Ophthalmology, University Hospital, Antwerp, Belgium, and the University Hospital, Ljubljana, Slovenia, and a private ophthalmology practice, Oudenaarde, Belgium. METHODS: Thirty-four eyes of 22 children had implantation of a bag-in-the-lens IOL. The ages ranged from 2 months to 14 years. Congenital cataract was present in 26 eyes, and persistent fetal vasculature (PFV) was concomitantly present in 4 eyes. Fifteen patients had bilateral cataract, and 6 had unilateral cataract. RESULTS: In 3 eyes, the IOL could not be properly implanted. In these cases, secondary intervention was necessary because of early posterior capsule opacification. The mean postoperative follow-up was 17.45 months +/- 17.12 (SD) (range 4 to 68 months). None of the children except those presenting with PFV had anterior vitrectomy during surgery. The optical axis remained clear during the follow-up in all patients who had successful IOL implantation. CONCLUSIONS: The bag-in-the-lens implantation technique in children and babies was safe and kept the visual axis clear after cataract surgery. In the near future, 4.0 or 4.5 mm IOLs will be available that may improve the success rate of IOL implantation in the small eyes of babies.