The Bedside Dysmorphologist

William Reardon, author of The Bedside Dysmorphologist: Classic Clinical Signs in Human Malformation Syndromes and their Diagnostic Significance, is Consultant Clinical Geneticist, at Our Lady’s Hospital for Sick Children, Crumlin, Dublin, Ireland. Dysmorphology is the study of congenital malformations. Often a health professional will take note of low set ears or deep set eyes and wonder whether it indicates a more serious genetic disorder. In his book Reardon provides an effective guide to identifying malformations and determining their clinical significance. In the excerpt below Reardon looks at Deep-Set Eyes.

Deep-Set Eyes

Recognizing The Sign An important sign, deep-set eyes are frequently the harbringer of wider concerns. The neonate generally opens his or her eyes voluntarily in the first day or two of life. Failure to do so may reflect photophobia or underlying eye malformation, such as microphthalmia. Tightly shut eyes, which require a speculum to expose the eye, are typical of deep-set eyes and should prompt a formal pediatric ophthalmologic evaluation. Deep-set eyes are best appreciated by viewing the face from the side. The usual bulge created by the globe is reduced in volume and there is often an associated skin crease extending laterally from the margin of the palpebral fissure.

Establishing a Differential Diagnosis In a neonate, convincingly deep-set eyes must prompt specific examination. Think of Freeman-Sheldon syndrome, in which microstomia and camptodactyly of the handsare the clinical giveaway features, and Rubenstein-Taybi syndrome, in which the broad thumbs and prominent nasal columella should secure the clinical diagnosis. Secure that you have clinically excluded these two recognizable phenotypes, consider now two specific genetic conditions, Lowe syndrome and chromosome 1p35 deletion. Lowe Syndrome is an x-linked condition of mental retardation, renal tubulopathy, and cataract, often associated with glaucoma. Hence, family is important, as are urinary investigation for nonspecific aminoaciduria and ophthalmologic evaluation. Female carriers generally have cortical opacities if no visual significance identifiable on slit amp examination. In contrast, chromosome 1p 36 deletion is the second most common microdeletion after 22q11. Look for low-set or horizontal eyebrows with loss of normal arched shape. Unexplained obesity is a frequent observation. The helices of the ears should be examined for asymmetry, thickening the helices, or pinna malformations. Hypotonia neonatal feeding concerns occurs, or delayed motor milestones in a child with deep-set eyes should stimulate specific specific investigation for this condition. Lenz michrophtlamic syndrome classicly presents itself with deep-set eyes. Inherited in x-linked dominant manner, a family history of cologoma, lens surgery, or retinal detachment offers valuable diagnostic support. Oligodontia should be sought in adult cases, and occasional skeletal features sch as radiolnar synostosis or polydactyly) are within the spectrum of malformations expected.

Investigations to Consider In Lowe syndrome be aware of the initial absence of aminoaciduria in urine during the neonatal period and repeat urinalysis after a few months. Elevated urinary retinal binding protein is the best single screening measure. Chromosme 1p36 deletions need specific cytogenetic analysis by targeted subtelmere studies, so discuss your clinical concerns with your laboratory. Lenz microphthalmia can be confirmed my mutation analysis of the BCOR gene of Xp27.