James E. Elder

Aetiology of congenital and paediatric cataract in an Australian population

Background/aim: Paediatric cataract is a major cause of childhood blindness. Several genes associated with congenital and paediatric cataracts have been identified. The aim was to determine the incidence of cataract in a population, the proportion of hereditary cataracts, the mode of inheritance, and the clinical presentation. Methods: The Royal Childrens Hospital and the Royal Victorian Eye and Ear Hospital have a referral base for almost all paediatric patients with cataracts in south eastern Australia. The database contains cases seen over the past 25 years. The medical histories of these patients were reviewed. Results: 421 patients with paediatric cataract were identified, which gives an estimated incidence of 2.2 per 10 000 births. Of the 342 affected individuals with a negative family history, 50% were diagnosed during the first year of life, and 56/342 (16%) were associated with a recognised systemic disease or syndrome. Unilateral cataract was identified in 178/342 (52%) of sporadic cases. 79 children (from 54 nuclear families) had a positive family history. Of these 54 families, 45 were recruited for clinical examination and DNA collection. Ten nuclear families were subsequently found to be related, resulting in four larger pedigrees. Thus, 39 families have been studied. The mode of inheritance was autosomal dominant in 30 families, X linked in four, autosomal recessive in two, and uncertain in three. In total, 178 affected family members were examined; of these 8% presented with unilateral cataracts and 43% were diagnosed within the first year of life. Conclusions: In the paediatric cataract population examined, approximately half of the patients were diagnosed in the first year of life. More than 18% had a positive family history of cataracts. Of patients with hereditary cataracts 8% presented with unilateral involvement. Identification of the genes that cause paediatric and congenital cataract should help clarify the aetiology of some sporadic and unilateral cataracts.

Retinal findings after head trauma in infants and young children.

BACKGROUND Many authorities believe that the finding of retinal hemorrhages in a child younger than 3 years of age with a history of head trauma, in the absence of an obvious cause for the injury, is pathognomonic of child abuse. To date, no studies have examined the prospective retinal examination of children who have had head trauma. The authors undertook such a study because the presence of retinal hemorrhage from any head trauma in children may have medicolegal diagnostic significance in differentiating accidental from nonaccidental trauma. METHODS Seventy-nine children younger than 3 years of age, each of whom experienced head injury, underwent an ophthalmologic assessment, which included a dilated funduscopic examination. RESULTS Seventy-five children sustained accidental head injuries and had normal funduscopic examinations. Three children had nonaccidental head injuries and all were found to have varying degrees of retinal hemorrhages. One child, with a normal fundus examination, had injuries that were of indeterminate cause. CONCLUSION The finding of retinal hemorrhages in a child with a head injury suggests a nonaccidental cause.

A novel mutation in the Connexin 46 gene causes autosomal dominant congenital cataract with incomplete penetrance

Congenital or paediatric cataract is a phenotypically and genetically heterogeneous disorder consisting of lens opacities in early life. Thirteen genes have been described for autosomal dominant congenital cataract (ADCC). These include genes for seven members of the crystallin family,1,2 which are responsible for the refractive index and transparency of the lens, two connexin genes3,4 and major intrinsic protein of the lens (MIP)5 which are involved in the transport directly between cells of small metabolites and water, respectively, the cytoskeletal protein beaded filament structural protein-2 (BFSP2),6 and transcription factors paired-like homeodomain transcription factor-3 (PITX3)7 and heat shock factor-4 (HSF4).8 Five additional loci have been described on chromosomes 1pter-p36.1,9 15q21-q22,10 17p13,11 17q24,12 and 20p12-q12.13 We used a linkage approach to investigate these 13 genes and five loci in a large pedigree from Victoria, Australia, with zonular pulverulent cataract with the aim of identifying the causative mutation. Ethics approval for this study was obtained from the Human Research Ethics Committees of the Royal Children’s Hospital, Melbourne, Australia, the Royal Victorian Eye and Ear Hospital, Melbourne, Australia, and the University of Tasmania, Hobart, Australia. ### Patient ascertainment and collection of genetic material The pedigree crch13 was identified through a database maintained by the Royal Children’s Hospital, Melbourne, Australia and the Royal Victorian Eye and Ear Hospital, Melbourne, comprising paediatric cataract patients from south-eastern Australia with any type of lens opacity.14 Written informed consent was obtained from all participating individuals or their guardians. When possible, family members were examined by one or more ophthalmologists (MGW, DAM, JEE, JEC, or IR-E). Due to the rural location of most family members, affection status was determined from medical records when direct examination was not feasible. In many cases pre-operative visual acuity was not available. Buccal mucosal swabs were either collected during examination …

Effects of acid suppression on microbial flora of upper gut

Decreased acid secretion, due to therapy or disease, predisposes to increased bacterial counts in gastric juice. As bacterial numbers increase, the number of nitrate-reducing strains and the concentration of luminal nitrite usually also increase. However, there is controversy (mainly because of assay problems) about whether decreased acid increases generation ofN-nitroso compounds: these may be produced by acid or by bacterial catalysis, and the relative contributions of each are still uncertain. Other potentially important factors include ascorbate secretion (can prevent nitrite conversion to nitroso compounds) and the particular spectrum of nitroso compounds produced. Nitrosation of several histamine H2-receptor antagonists has been demonstrated experimentally, but under conditions that are very unlikely to be encountered clinically. Some acid suppressant therapies have been claimed to aid eradication ofHelicobacter pylori, but more work is needed to evaluate this. If ulcer treatment regimens do not also address eradication ofH. pylori (when present), gastritis will progress, and the recently documented association betweenH. pylori and gastric carcinoma needs to be considered. Enteric flora probably also increase if acid secretion is markedly reduced: this does not appear to have nutritional consequences but probably reduces the resistance to occasional infections, of which cholera is the best documented.

Prevalence of CYP1B1 mutations in Australian patients with primary congenital glaucoma

Analysis of CYP1B1 in primary congenital glaucoma (PCG) patients from various ethnic populations indicates that allelic heterogeneity is high, and some mutations are population specific. No study has previously reported the rate or spectrum of CYP1B1 mutations in Australian PCG patients. The aim of this study is to determine the frequency of CYP1B1 mutations in our predominately Caucasian, Australian cohort of PCG cases. Thirty‐seven probands were recruited from South‐Eastern Australia, along with 100 normal control subjects. Genomic DNA was extracted and the coding regions of CYP1B1 analysed by direct sequencing. Sequence analysis identified 10 different CYP1B1 disease‐causing variants in eight probands (21.6%). Five subjects were compound heterozygotes, two subjects heterozygous and one homozygous for CYP1B1 mutations. Three missense mutations are novel (D192Y, G329D, and P400S). None of the novel mutations identified were found in normal controls. One normal control subject was heterozygous for the previously reported CYP1B1 R368H mutation. Six previously described probable polymorphisms were also identified. Mutations in CYP1B1 account for approximately one in five PCG cases from Australia. Our data also supported the high degree of allelic heterogeneity seen in similar studies from other ethnic populations, thereby underscoring the fact that other PCG‐related genes remain to be identified.

Primary infantile glaucoma in an Australian population

Background: Primary infantile glaucoma presents rarely, but can be responsible for significant visual morbidity. There is little information on the clinical features and visual outcome of a pure population of primary infantile glaucoma, as opposed to a mixed population of primary and secondary glaucoma or combined group of those with trabeculodysgenesis and iridotrabeculodysgenesis.

Retinal haemorrhage in accidental head trauma in childhood

Abstract  Twenty‐five children (age range 1.2–14.5 years) who sustained accidental head injury requiring admission to hospital were prospectively examined for evidence of retinal haemorrhage. In no case were retinal haemorrhages detected. It is suggested that accidental head injury seldom results in retinal haemorrhage and that the finding of retinal haemorrhage in a child with a head injury should prompt suspicion of abuse.

Retinoblastoma in Victoria, 1976−2000: changing management trends and outcomes

Purpose: To describe changes in the management of retinoblastoma in Victoria and to review the effect of newer, conservative treatments on preservation of eyes, visual outcome and mortality by comparing a similar group of patients treated over successive time intervals.

Long-term visual outcome after chemotherapy for optic pathway glioma in children: Site and age are strongly predictive

Optic pathway gliomas (OPGs) are commonly noted in pediatric oncology services. Radiotherapy is effective at controlling tumors, but has many undesirable late effects, especially in patients with neurofibromatosis. Chemotherapy is commonly used to preserve vision and delay or eliminate the need for radiotherapy. Despite visual threat being a common reason to initiate chemotherapy in patients with OPG, reports of visual outcome after chemotherapy are not common and reports of long‐term visual outcome are even scarcer.

Visual Improvement Despite Radiologically Stable Disease After Treatment With Carboplatin in Children With Progressive Low-grade Optic/thalamic Gliomas

Background The purpose of this study was to examine the clinical and radiologic response to carboplatin by children with progressive optic/thalamic gliomas. Patients and Methods Between July 1997 and July 1999, 12 consecutive children were treated with monthly carboplatin for progressive optic/thalamic gliomas. Results Five children have completed 12 cycles of carboplatin and five children are currently receiving treatment. Two children had progressive disease noted both clinically and radiologically. Nine children have stable radiologic disease and one child has had a partial radiologic response to chemotherapy. Eight children have had regular visual assessments. Four children (three with stable radiology and one with a partial radiologic response) have had improvement in their vision. Three children with radiologically stable disease have had no change in vision. One child has had deterioration in vision despite radiologically stable disease. Conclusions The results suggest that the clinical response of optic/thalamic gliomas to carboplatin, as measured by visual acuity and visual fields, may be better than predicted by radiologic assessment. These data suggest that a prospective clinical study is warranted of the role of carboplatin in children with progressive optic/thalamic gliomas and visual impairment.