Optic atrophy in children: Current causes and diagnostic approach.

BACKGROUND/AIMS: Optic atrophy is one of the leading causes of sight impairment in children. It frequently poses a diagnostic challenge, as it can be caused by many ocular and systemic conditions. We aimed to determine the current causes of optic atrophy at our centre and to describe the use of investigations, including molecular genetic testing. METHODS: We reviewed the medical records of children with optic atrophy seen at Moorfields Eye Hospital between 2010 and 2015. We recorded demographic data, reason for referral, history, investigations and diagnosis. RESULTS: We studied 143 cases aged below 16 years. A cause could be identified in all cases. Taking a full history was the most important part of the diagnostic workup, identifying a cause in 96 (67%) children. A developmental disorder of the brain and/or optic nerve, sometimes with retinal involvement, was the commonest cause (n = 33, 23%), followed by inheritable optic neuropathies (n = 27, 19%). Other causes included perinatal insults (n = 18, 13%), post-infectious or post-inflammatory conditions (n = 18, 13%), accidental or abusive trauma (n = 14, 10%) and inheritable retinal dystrophies (n = 13, 9%). Rare conditions included neurodegenerative disorders (n = 7, 5%), skeletal developmental disorders such as rickets (n = 4, 3%), tumours (n = 4, 3%), ischaemic events including large optic nerve head drusen (n = 4, 3%) and toxic events/metabolic conditions (n = 1, 0.7%). CONCLUSION: In this series, an underlying cause could be identified in all cases. Taking a comprehensive antenatal, perinatal, postnatal and family history will indicate a probable diagnosis in two-thirds of children, and targeted ancillary tests may identify the cause in most remaining cases.

Clinical features affecting final adult height in patients with pediatric-onset Crohn's disease.

BACKGROUND: Growth failure is a recognized complication of pediatric-onset Crohn's disease, but there are few data on final adult height. OBJECTIVE: Our purpose with this work was to determine adult height and the clinical features that influence long-term growth impairment. METHODS: We retrospectively studied 123 patients with Crohn's disease (65 male and 58 female) who had reached adult height. All of the case subjects were diagnosed before age 16.0 years. Heights were converted to SD scores and univariate analysis performed of factors postulated to influence final height, that is, interval from onset of symptoms to diagnosis, prepubertal onset of symptoms, gender, jejunal disease present at diagnosis, systemic steroid therapy, intestinal surgery, and midparental height SD scores. Significant univariate factors were additional analyzed in regression models. RESULTS: Mean height deficit at diagnosis was -0.50 SD scores, which improved to -0.29 SD scores at final height. Mean final height compared with target height, calculated from parental height, was -2.4 cm (range: -20.0 to 9.0 cm). Nineteen percent of the case subjects achieved a final height >8.0 cm below target height. The length of the interval between symptom onset and diagnosis correlated negatively with height SD scores at diagnosis. Height SD scores at diagnosis were related to final height SD scores, independent of midparental height. The presence of jejunal disease was negatively related to final height. CONCLUSIONS: Mean final adult height showed a modest deficit compared with target height, but in one fifth of patients, final height was significantly less than target height. Earlier diagnosis and improved treatment of jejunal disease would be likely to improve final height.

Intestinal inflammation-induced growth retardation acts through IL-6 in rats and depends on the -174 IL-6 G/C polymorphism in children.

Inflammatory diseases frequently impair linear growth. Crohn's disease inhibits growth in up to one third of affected children. In rats with trinitrobenzenesulphonic acid-induced colitis, 40% of growth impairment is attributable to inflammation, with the rest being due to undernutrition. In transgenic mice without inflammation, raised IL-6 retards growth, suppressing insulin-like growth factor (IGF)-I. We hypothesized that IL-6, induced by intestinal inflammation, suppresses growth and inhibits IGF-I expression. Therefore, an anti-IL-6 Ab was given to rats with trinitrobenzene-sulphonic acid colitis. The Ab did not improve nutrient intake or decrease inflammation compared with untreated disease controls, but it significantly restored linear growth (P = 0.023) and increased IGF-I (P = 0.05). In humans, the IL-6 -174 G/C promoter polymorphism affects IL-6 transcription, with the GG genotype inducing the greatest IL-6 levels. Because IL-6 is increased in Crohn's disease, we further hypothesized that growth failure would vary with the IL-6 -174 genotype. At diagnosis, among 153 children with Crohn's disease, those with the IL-6 GG genotype were more growth-retarded than those with the GC or CC genotypes (height SD score, -0.51 vs. -0.10; P = 0.031). Also, the patients with the IL-6 GG genotype had higher circulating levels of C-reactive protein, an IL-6-induced product (36 vs. 18 mg/dl, P = 0.028). However, their risk of developing Crohn's disease was similar to other genotypes when compared with 351 healthy controls (P = 0.7). Thus, the IL-6 -174 genotype mediates growth failure in children with Crohn's disease.