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Isolated strabismus affects 1–5% of the general population 1 . Most forms of strabismus are multifactorial in origin; although there is probably an inherited component, the genetics of these disorders remain unclear. The congenital fibrosis syndromes (CFS) represent a subset of monogenic isolated strabismic disorders that are characterized by restrictive ophthalmoplegia, and include congenital fibrosis of the extraocular muscles (CFEOM) and Duane syndrome (DURS) 2 . Neuropathologic studies indicate that these disorders may result from the maldevelopment of the oculomotor (nIII), trochlear (nIV) and abducens (nVI) cranial nerve nuclei 3 , 4 , 5 . To date, five CFS loci have been mapped ( FEOM1, FEOM2, FEOM3 , DURS1 and DURS2 ) 6 , 7 , 8 , 9 , 10 , but no genes have been identified. Here, we report three mutations in ARIX (also known as PHOX2A ) in four CFEOM2 pedigrees. ARIX encodes a homeodomain transcription factor protein previously shown to be required for nIII/nIV development in mouse and zebrafish 11 , 12 . Two of the mutations are predicted to disrupt splicing, whereas the third alters an amino acid within the conserved brachyury-like domain 13 , 14 . These findings confirm the hypothesis that CFEOM2 results from the abnormal development of nIII/nIV (ref. 7 ) and emphasize a critical role for ARIX in the development of these midbrain motor nuclei 13 , 14 , 15 , 16 , 17 , 18 , 19 .

We describe a new dysmorphic syndrome in an inbred Saudi Arabian family with 21 members. Five males and one female have similar craniofacial features including wide open calvarial sutures with large and late-closing anterior fontanels, frontal bossing, hyperpigmentation with capillary hemangioma of the forehead, significant hypertelorism, and a broad and prominent nose. In addition, these individuals have Y-shaped sutural cataracts diagnosed by 1-2 years of age. No chromosomal or biochemical abnormalities were identified. A genome-wide scan was performed, and two-point LOD score analysis, assuming autosomal recessive inheritance, detected linkage to chromosome 14q13-q21. The highest LOD scores were obtained for marker GATA136A04 (LOD=4.58 at theta=0.00) and for the adjacent telomeric marker D14S1048 (LOD=4.32 at theta=0.00). Multipoint linkage analysis resulted in a maximum LOD score of 5.44 between markers D14S1048 and GATA136A04. Model independent analysis by SIBPAL confirmed linkage to the same chromosomal region. Haplotype analysis indicated that all affected individuals were homozygous for the interval on chromosome 14q13-q21 with two recombinants for D14S1014 (centromeric) and one recombinant for D14S301 (telomeric). These recombinations limit the disease locus to a region of approximately 7.26 Mb. Candidate genes localized to this region were identified, and analysis of PAX9 did not identify mutations in these patients. The unique clinical phenotype and the mapping data suggest that this family represents a novel autosomal recessive syndrome.

The treatment of congenital nasolacrimal duct (NLD) obstruction continues to be a subject of controversy. Some authors advocate early probing and irrigation in an office setting, whereas others recommend that the procedure be performed under general anesthesia when the child is at least 1 year old. The focus of this study was to compare the results of probing and irrigation of congenital NLD obstruction among children younger than 1 year of age, those 1 to 2 years of age, and those older than 2 years. The author reviewed the records of 120 patients, ranging in age from 3 weeks to 30 years, with 153 cases of NLD obstruction. Eighty-five patients (110 cases of NLD obstruction) underwent probing and irrigation. Complications of NLD obstruction occurred in 12 patients; 75% of these patients were younger than 1 year of age. In group 1 (patient age < 1 year) there were 37 probings with 1 failure (3%). Group 2 (patient age = 1-2 years) had 43 probings and 5 failures (12%). In group 3 (patient age > 2 years), 30 NLDs were probed with 2 failures (7%). However, these differences were not significant (P = .13 between groups 1 and 2; P = .42 between groups 1 and 3). In this study, the postponement of probing and irrigation for congenital NLD obstruction beyond the age of 1 year did not result in an increased rate of failures or complications.

It is currently fashionable to attribute changes in organ shape during development to the actions of microtubules and microfilaments on individual cells of the organ in question. In the case of the eye lens it has been proposed that cellular elongation under the influence of microtubules and/or apical contraction by microfilaments are responsible for the remodeling of the originally low cuboidal ectoderm into the tall and wedge-shaped presumptive lens cells. Invagination of the lens is thought to follow automatically. These ideas cannot account for certain observations on lens morphogenesis, such as the relatively fixed diameter of the organ rudiment during early development, which is incompatible with the supposed contraction of the rudiment. We found that the area of contact between presumptive lens and optic cup does become fixed after a few hours of \"induction.\" There is a remarkable correlation in time between this fixation, and the process of lens cell elongation and increase in lens cell density. We calculated that the latter two can, in fact, be accounted for by population pressure caused by continued cell division within the defined area of the lens rudiment. A mathematical model along these lines was developed, which explains lens invagination on the basis of cell number and size, extent of the area of contact between ectoderm and optic cup, and cell population doubling times. We hypothesize that the prevention of lateral cell spreading within the lens territory, after the contact area becomes fixed, is a function of the build-up in extracellular materials in this area during the \"induction period.\" Both lens rudiment and presumptive retina contribute to this extracellular matrix.

To perform a review of the literature comparing the safety of bilateral simultaneous lensectomies in children versus the risk of more than one general anesthesia within a short time frame, and to study the results of bilateral surgery in a small group of patients. Bilateral simultaneous lensectomies were performed in 9 children (18 eyes), in whom increased anesthetic risks warranted this approach. There were no postoperative complications for at least 6 months. Data in the current literature on endophthalmitis after cataract surgery and on the risks of repetitive anesthesia are inadequate to weigh the risk of bilateral endophthalmitis against the reduced risk of one anesthesia versus two and the advantages of simultaneous early visual rehabilitation. Until such information becomes available, simultaneous removal of bilateral infantile cataracts should probably be reserved for selected cases where the anesthetic risk is higher than average.

A 4-month-old infant received an accidental intraocular injection of methylprednisolone while undergoing penetrating keratoplasty for congenital, hereditary endothelial dystrophy. This was not discovered until 4 months later, at which time the intraocular pressure (IOP) was increasing and an early cataract was forming. A lensectomy and vitrectomy were performed when the child was 12 months old. The IOP remained higher than that of the fellow eye, but the recovery was otherwise uneventful. This indicates that intraocular depot steroid may be tolerated, except when there is the occurrence of known pharmacologic side effects.

In this study, an easily palpable landmark, the supraorbital notch or foramen, was used to simplify the localization of the nasolacrimal duct during the probing procedure. The notch was palpated in 50 patients of a pediatric clinic. The topographic anatomy of the notch in relation to the lacrimal drainage system was studied in 10 skulls. The supraorbital notch is a convenient landmark for the guidance of a probe into the nasolacrimal canal. This technique should reduce the failure rate of probing without the need for infracturing of the lower turbinate or silicone intubation.