Third case of cerebral, ocular, dental, auricular, skeletal anomalies (CODAS) syndrome, further delineating a new malformation syndrome: first report of an affected male and review of literature.

CODAS syndrome (MIM# 600373) is a rare multiple congenital anomalies syndrome. The disorder is highly distinctive with characteristic features consisting of developmental delay, cataracts, unusual enamel projections, overfolded and crumpled ears, epiphyseal dysplasia, and dysmorphic features (grooved nose, ptosis). To date, there have been two affected female children reported. The first was a Canadian girl of Mennonite descent, reported by our group, and the second was a girl from Brazil. The etiology and pattern of inheritance of CODAS is unknown. Herein we report a third affected child, a Canadian male infant of Mennonite ancestry. The child, now two years old, exhibits ptosis, cataracts, overfolded ears, grooved nasal tip, dental projections, developmental delay, and characteristic skeletal anomalies. The findings are characteristic for CODAS syndrome. All investigations including karyotype, metabolic screening, peroxisomal studies, and studies of cholesterol biosynthesis were normal. The underlying defect responsible for CODAS syndrome remains unknown. Many of the features suggest a possible underlying collagen gene defect. The fact that this child is the second child from the Manitoba Mennonite community, a genetic isolate, suggests the possibility of autosomal recessive inheritance. To date, there has not been a familial recurrence.

Effect of nebulized ipratropium bromide on intraocular pressures in children.

STUDY OBJECTIVE: To evaluate the effects of nebulized ipratropium bromide on intraocular pressures and pupillary responses in children with asthma. DESIGN: A double-blind, randomized, crossover study. SETTING: Children's Hospital of Winnipeg, University of Manitoba. PATIENTS OR PARTICIPANTS: Age 6 to 17 years with asthma. INTERVENTION: Nebulized ipratropium bromide added to albuterol sulfate, albuterol alone, or saline solution was given by face mask and nebulizer. Before and 0.5 h after nebulization, intraocular pressures (mm Hg), pupillary size (mm), and pupillary responses were measured. In a subsequent open study, patients who had been admitted to hospital with acute asthma who were treated with nebulized ipratropium bromide were recruited for measurement of intraocular pressures, pupillary size, and pupillary responses. MEASUREMENTS AND RESULTS: Twenty patients completed the double-blind study, and 26 patients completed the open study. There were no changes in intraocular pressures, pupillary size, or pupillary response after any treatment on any study day in either the double-blind or the open studies. CONCLUSION: In children with asthma, who have no pre-existing ocular abnormalities, the risk of an adverse reaction to nebulized ipratropium bromide delivered by face mask inadvertently absorbed in the eye is extremely small.

Absence of posterior subcapsular cataracts in young patients treated with inhaled glucocorticoids.

The prevalence of posterior subcapsular cataracts in young patients receiving inhaled glucocorticoids for treatment of chronic asthma is unknown. In a cross-sectional study, slit-lamp examinations were done on 95 consecutive young patients who were taking inhaled beclomethasone or budesonide. No posterior subcapsular cataracts were found. The median age of the patients was 13.8 (range 5.8-24.8). The median dose of inhaled beclomethasone or budesonide was 750 micrograms/day (range 300-2000), or 12.9 micrograms/kg per day (range 7.5-34.2). The median duration of treatment was 5 years (range 1-15). 77% of the patients had not used oral glucocorticoids in the year preceding the examination. This study suggests that routine screening for posterior subcapsular cataracts in this patient population is not warranted.

New familial syndrome of unilateral upper eyelid coloboma, aberrant anterior hairline pattern, and anal anomalies in Manitoba Indians.

We report on 6 (3 male, 3 female) Manitoba Indian children with hypertelorism and variable combinations of unilateral eye malformations, aberrant anterolateral scalp hairline, and nasal and anal anomalies. These children belong to 4 related families. The parents and 7 other sibs are clinically unaffected. The family histories are otherwise unremarkable. The presence of 2 major malformations in sibs and related individuals (with unaffected parents) suggests that this is a newly described pleiotropic autosomal recessive syndrome. The differential diagnosis includes cryptophthalmos syndrome and several other related malformation syndromes. Although multifactorial determination cannot be excluded, the inbred, isolated population and distribution make autosomal recessive inheritance more likely.

Newly recognized syndrome of cerebral, ocular, dental, auricular, skeletal anomalies: CODAS syndrome--a case report.

We report on a child with a unique constellation of congenital anomalies suggesting a new syndrome. These consist of developmental delay; craniofacial abnormalities, including bilateral cataracts, ptosis, median nasal groove, malformed ears with associated neurosensory hearing loss; dental anomalies consisting of anomalous cusp morphology with unusual pointed extensions and delayed tooth eruption; short stature with marked delay in epiphyseal ossification; coronal clefts involving vertebrae T11-S2; and dislocated hips. A literature search and use of a computer-assisted syndrome-identification program failed to uncover an identical case.

Allgrove syndrome: an autosomal recessive syndrome of ACTH insensitivity, achalasia and alacrima.

Allgrove syndrome (isolated glucocorticoid deficiency, achalasia and alacrima) was found in eight members of an inbred French Canadian/North American Indian pedigree. The high degree of consanguinity supports an autosomal recessive mode of inheritance for this disorder. Six patients presented with hypoglycaemia and other evidence of cortisol deficiency between 2.5 and 8 years of age; however, two others became cortisol deficient after initial testing showed normal cortisol responses to ACTH, evidence that the glucocorticoid insufficiency of this syndrome may not be congenital, but may develop as late as the third decade. No evidence of mineralocorticoid deficiency has been found during 65 patient-years of follow-up. Alacrima was the earliest and most consistent clinical sign of Allgrove syndrome. Other manifestations of peripheral or autonomic neuropathy were found in four patients. The patients showed similar facial features, and three had significant velo-pharyngeal incompetence. All showed oesophageal dysmotility even in the absence of symptomatic dysphagia. In-vitro studies of lymphocyte ACTH binding showed no differences from normal controls. If such lymphocyte binding, as has been suggested, reflects adrenal ACTH receptor activity, these data would suggest that the glucocorticoid deficiency of Allgrove syndrome is not the result of a defect in that receptor. However, the observation that ACTH does not elicit increased adenylate cyclase activity even in normal lymphocytes casts considerable doubt on the physiological significance of ACTH binding to lymphocytes. It seems likely, therefore, that true ACTH receptors are not expressed on peripheral lymphocytes, and any conclusions regarding a possible receptor defect in Allgrove syndrome must await studies of receptor expression on adrenal cell membranes.

Posterior fixation suture operation (fadenoperation).

The posterior fixation operation affords the ophthalmologist an additional procedure for the correction of DVD, nystagmus blockage syndrome and abnormal distance/near relationships associated with esodeviations. The authors report that 95% of the patients had improved their control of manifest DVD. The results of surgery for the nystagmus blockage syndrome and abnormal distance/near relationship patients remain inconclusive. The posterior fixation procedure, while technically difficult, may be performed safely by the experienced surgeon. Refinements of the surgical technique are described.

External carotid-cavernous fistula in an infant.

A 7-week-old infant developed a nontraumatic fistula of the external carotid artery and the cavernous sinus. Therapeutic embolization produced an uncomplicated clinical and angiographic cure. Treatment was prompted by the availability of new methods of treatment and our hope of preventing irreversible anatomic and visual sequelae.