[Systemic and ophthalmological findings in Cornelia de Lange syndrome]. / Objawy ogólne i okulistyczne zespolu Cornelii de Lange.

Cornelia de Lange Syndrome (CdLS, de Lange syndrome, Brachmann-de Lange syndrome), is a relatively rare genetic disorder, characterized by set of clinical abnormalities concerning different organs and systems. Phenotypic diagnosis is based on a specific dysmorphic features seen after the birth. We described a genetic basis, hereditary patterns, characteristic dysmorphic features and the most common clinical findings of patients Cornelia de Lange Syndrome concerning eye and vision, hearing, cardiovascular, respiratory, gastrointestinal, genitourinary, skeletal and psychomotor development.

Exclusion of positional candidate gene coding region mutations in the common posterior polymorphous corneal dystrophy 1 candidate gene interval.

PURPOSE: Posterior polymorphous corneal dystrophy (PPCD) is an autosomal-dominant disorder of the corneal endothelium associated with visually significant corneal edema and glaucoma. Statistical genetic analysis of 4 families with PPCD has demonstrated linkage to a 2.4 cM common support interval on chromosome 20 bordered by the markers D20S182 and D20S139. We sought to identify the genetic basis of PPCD linked to chromosome 20 (PPCD1) by screening the 26 positional candidate genes between these markers in a family previously mapped to the PPCD1 region. METHODS: The coding regions of the 26 positional candidate genes mapped to the common PPCD1 support interval were amplified and sequenced in affected and unaffected individuals from a family previously linked to the PPCD1 locus. Nine other genes positioned just outside of the common PPCD1 support interval but within the autosomal-dominant congenital hereditary endothelial dystrophy interval were also screened. RESULTS: Four DNA sequence variants in 3 of the positional candidate genes demonstrated complete segregation with the affected phenotype: p.Thr109Thr (rs6111803) in OVOL2, p.Arg56Gln (novel variant-RPSnovel) in RPS19P1, and p.Thr85Thr (rs1053834) and p.Pro99Ser (rs1053839) in C20orf79. Each of these 4 sequence variants demonstrated significant linkage with the affected phenotype in this family (P = 2.5 x 10 for RPSnovel, rs1053834 and rs1053839; P = 8.6 x 10 for rs6111803). However, we also identified each of these 4 sequence variants in > or = affected control individuals. The haplotype on which the disease-causing mutation is segregating was found to have a population frequency of 4.2% in the CEPH HapMap trios. Although a number of other previously described and novel single nucleotide polymorphisms were identified in the 35 positional candidate genes located within the PPCD1 and congenital hereditary endothelial dystrophy intervals, none segregated with the affected phenotype. CONCLUSIONS: We report the absence of a presumed pathogenic coding region mutation in the common PPCD1 support interval. Although minor alleles of 4 single nucleotide polymorphisms were identified that segregated with the affected phenotype, the relatively high frequency of each minor allele in the general population indicates that none is a candidate for the causal variant for PPCD. Instead, the causal variant is most likely a coding region deletion or a variant in a noncoding region of the PPCD1 common support interval.

Congenital hyposomatotropism in a domestic shorthair cat presenting with congenital corneal oedema.

A six-month-old, female, domestic shorthair cat was presented with a history of failure to grow and bilateral corneal opacity caused by corneal oedema. Congenital hyposomatotropism and possible secondary hypothyroidism were diagnosed on the basis of fasting serum levels of insulin-like growth factor-1 and thyroxine levels, respectively. These endocrinopathies are rare in the cat and have not been reported to cause ocular signs. The cat died during investigation of these diseases, and histopathological examination of the eyes showed significantly reduced corneal endothelial cell density and number of corneal epithelial cell layers when compared with age-matched healthy control corneas. These changes were implicated in the development of the corneal oedema.

[Glaucoma with aniridia and isolated congenital glaucoma in siblings: contribution and limits of genetics]. / Glaucome secondaire à une aniridie et glaucome congénital isolé dans une même fratrie: apports et limites de la génétique.

INTRODUCTION: Congenital glaucoma associated with aniridia and primary congenital glaucoma are regarded as different entities. Indeed, the abnormalities of the angle's structures as well as the genes involved are different. We report the observation of two sisters presenting these two types of glaucoma with particular attention paid to the importance and the difficulty of genetic counseling. OBSERVATIONS: Child L, with no particular family history, had presented bilateral aniridia complicated by bilateral glaucoma since birth. In addition to medical and surgical treatment, general and genetic investigations were undertaken that revealed no abnormalities. No microdeletion of the gene PAX6 responsible for the aniridia was found. Consequently, the genetic advice was in favor of a second pregnancy for this couple. At birth, L's sister also presented bilateral congenital glaucoma, which was isolated, without aniridia. New genetic investigations were carried out but no abnormalities in PAX6, nor in FOXC1 or PITX2 involved in the development of the anterior chamber, were found. Moreover, the haplotypes for aniridia locus AN2 inherited by the two sisters were different, proof that this gene could not be responsible for the glaucoma. DISCUSSION: At L's birth, the hypothesis retained was that she was a sporadic case whose gene mutation could not be identified (which happens in 50% of sporadic cases). The risk for the second pregnancy was negligible, although not null. The primary congenital glaucoma presented by L's sister remains unexplained in the context of aniridia and the role of the PAX6 gene was eliminated. The study of PITX2 and FOXC1 genes involved in anterior segment dysgenesis proved that they were also not involved. Thus, this observation evokes the responsibility of a gene other than PAX6 in aniridia, which could also have a role in isolated congenital glaucoma. CONCLUSION: Analysis of congenital pathologies from a more genetic than clinical point of view seems to progressively break down the barriers established between the various phenotypes of hereditary congenital anomalies. Even if the association of aniridia and primary congenital glaucoma in siblings is reported here for the first time, it does not appear so extraordinary if one considers the complexity of the anterior chamber's development, which involves many genes, most of them still unidentified to date.

Aniridia and Brachmann-de Lange syndrome: a review of ocular surface and anterior segment findings.

PURPOSE: To review the ocular surface and anterior segment findings in Brachmann-de Lange syndrome and describe a new case involving aniridia and congenital glaucoma. METHODS: A newborn presented 2 days after birth with bilateral cloudy corneas, photophobia, and epiphora. We provide a 5-year descriptive history and clinical course with review of the literature on Brachmann-de Lange syndrome. RESULTS: Multiple ocular surgeries were performed for ocular sequelae from aniridia and congenital glaucoma including Ahmed valve placement and penetrating keratoplasties in both eyes. At 5.5 years of age, the child had a clear graft OD and amblyopia from graft failure OS following recurrent graft infections. A review of Brachmann-de Lange syndrome found 43 patients with ocular surface and anterior segment findings. The most common findings included conjunctivitis, blepharitis, microcornea, and corectopia. Aniridia and congenital glaucoma were not previously reported with Brachmann-de Lange syndrome. CONCLUSIONS: Ocular surface and anterior segment abnormalities must be considered when examining patients with Brachmann-de Lange syndrome. Ocular findings may include vision-threatening anomalies, as in our case with aniridia and congenital glaucoma. To our knowledge, these findings are previously unreported in Brachmann-de Lange syndrome.