LOXL3 novel mutation causing a rare form of autosomal recessive Stickler syndrome.

Stickler syndrome is a collagenopathy that is typically inherited as autosomal dominant disease caused by monoallelic mutations in COL2A1, COL11A2, and COL11A1. Rarely, biallelic mutations in COL9A1, COL9A2, and COL9A3 cause an autosomal recessive Stickler syndrome. One previous report described two siblings with Stickler syndrome and a homozygous mutation in LOXL3, suggesting that biallelic mutations in LOXL3 can also cause autosomal recessive Stickler syndrome. LOXL3 is a member of the lysyl oxidase family of genes which encode enzymes oxidizing the side chain of peptidyl lysine permitting the covalent crosslinking of collagen and elastin chains. Therefore, LOXL3 deficiency is expected to result in collagen defect. Furthermore, Loxl3 deficient mouse model demonstrated features overlapping with Stickler syndrome. In this report, we describe a child and his father who had clinical features consistent with Stickler syndrome and found to have a homozygous novel mutation c.1036C>T (p.Arg346Trp) in LOXL3. This report not only supports that biallelic LOXL3 mutations cause autosomal recessive Stickler syndrome, but also further delineates the phenotype associated with LOXL3 mutations. In addition, the family described here shows an interesting example for pseudodominance, which can be observed in recessive diseases when one parent is affected and the other is heterozygous carrier.

Megalocornea and bilateral developmental cataracts.

We present the case of a 9-year-old boy with megalocornea and juvenile cataracts. Bilateral lens aspiration and acrylic intraocular lens (IOL) implantation were performed under general anesthesia. After the surgery, both IOLs gradually decentered. Posterior capsule opacification was a further complication, necessitating bilateral neodymium:YAG (Nd:YAG) capsulotomy under local anesthesia. Five years after the Nd:YAG capsulotomy, the decentered IOLs remained in the same position and the vision remained stable with glasses. Cataract extraction in megalocornea is difficult, and complications are frequent. The type of IOL, IOL size, and need for surgery should be carefully considered.

Retinal hemorrhages in meningococcal septicemia.

PURPOSE: Meningococcal septicemia is associated with coagulopathy and hemorrhagic tendency. We carried out this study to determine the incidence of retinal hemorrhages in meningococcal septicemia. METHODS: This was a prospective study involving all children admitted to the Sheffield Children's Hospital, Sheffield, England, with a diagnosis of meningococcal septicemia. Confirmation of meningococcal infection was by blood culture or DNA analysis using polymerase chain reaction. The children underwent ocular examination including dilated fundus examination by direct and indirect ophthalmoscopy. Details of their coagulation status were also obtained. RESULTS: Twelve children (mean age, 4.5 years) with a confirmed diagnosis of meningococcal septicemia were included. All children had coagulopathy. Retinal hemorrhages were found in 5 children (42%). The disease was fatal in 3 children. Group C meningococcus was responsible for the infection in all those with retinal hemorrhages and those with fatal outcome. CONCLUSIONS: Retinal hemorrhage is a common feature in meningococcal septicemia. Ophthalmic evaluation should be part of the assessment of children with meningococcal septicemia. Future studies on meningococcal disease should include retinal hemorrhage as another parameter in the assessment. This should help us to understand the role of retinal hemorrhage in the prognosis of this serious disease.