Pediatrics: Developmental Biology

Conditions Studied

The Human Developmental Genetics Laboratory is actively studying genes involved in ocular and craniofacial development. Conditions of particular interest include:

• Anterior segment dysgenesis (ASD) disorders encompass a wide variety of developmental conditions affecting the cornea, iris, and lens and typically associated with an increased risk of glaucoma. A number of genes has been associated with ASD conditions, including B3GALTL, BMP4, CYP1B1, FOXC1, FOXE3, PITX2, and PITX3.
• Anophthalmia/microphthalmia (A/M) refers to a missing or small eye and may be associated with other ocular or systemic anomalies. A number of genes have been associated with A/M, including BMP4, FOXE3, OTX2, PITX3, SOX2, VSX2.
• Axenfeld-Rieger syndrome is a specific combination of anterior segment anomalies including posterior embryotoxon, iris malformation, corectopia/polycoria, irido-corneal adhesions, and ~50% risk for glaucoma. Common systemic abnormalities include craniofacial dysmorphism with maxillary hypoplasia, hypodontia, and umbilical anomalies (typically associated with PITX2 mutations); hearing loss and heart anomalies are also reported (typically associated with FOXC1 mutations).
• Cataracts are lens opacities which interfere with vision. Over 30 genes are known to be associated with congenital/juvenile cataracts, but the exact frequencies of mutations in these genes are not known and many cases are still awaiting molecular diagnosis.
• Glaucoma is damage to the optic nerve resulting in vision loss, often associated with elevated intraocular pressure (IOP). Congenital glaucoma refers to glaucoma present at birth (or shortly after) and is associated with mutations in CYP1B1. Glaucoma is often associated with anterior segment dysgenesis.
• Myopia, or nearsightedness, affects a large portion of the population. High myopia (prescription of >-6.00) is of particular interest in identifying genetic contributions to myopia.
• Optic nerve atrophy/hypoplasia refers to underdevelopment of the optic nerve.
• Peters anomaly is a developmental defect characterized by the triad of central corneal opacity, defects in the posterior layers of the cornea, and lenticulo-corneal and irido-corneal adhesions. Genes linked to Peters anomaly include CYP1B1, FOXC1, PAX6, and PITX2.
• Peters-plus syndrome is an autosomal recessive disorder associated with ocular and systemic defects and caused by mutations in B3GALTL. Classic features include Peters anomaly, short stature, and short hands and limbs; other anomalies commonly seen include distinctive facial features, cleft lip and/or cleft palate, hearing loss, abnormal ears, heart defects, genitourinary anomalies, variable degrees of mental retardation, and central nervous system abnormalities, including hydrocephalus.
• SHORT syndrome is characterized by Short stature, Hyperextensibility of joints or inguinal Hernia, Ocular depression, Rieger anomaly, and delay in dental eruption (Teeth). Recently, deletion of BMP4 and surrounding genes has been linked with SHORT syndrome.

In addition to the conditions described above, we are interested in other eye disorders which affect multiple family members.

Please contact us if you encounter a family with one of these conditions for more information about enrolling the family into our study.