Recessive mutations in this glucosyltransferase result in Peters plus syndrome, typically associated with Peters anomaly, short stature, and short hands/limbs, along with other systemic anomalies.
Heterozygous disruption of BMP4, an important signaling molecule, by deletion/mutation causes variable ocular (anophthalmia/microphthalmia or anterior segment dysgenesis), digital (polydactyly or syndactyly), brain anomalies, and poor growth. Recently, deletion of BMP4 was linked with SHORT syndrome.
This cytochrome P450 gene is involved in autosomal recessive congenital glaucoma; occasional cases of anterior segment dysgenesis along with congenital glaucoma have been reported.
Heterozygous deletions/mutations in this transcription factor are seen in Axenfeld-Rieger syndrome with isolated ocular features or ocular, hearing, and heart defects.
A forkhead box transcription factor, dominant mutations result in anterior segment dysgenesis and cataract while recessive mutations cause microphthalmia with sclerocornea.
Heterozygous deletion/mutation of OTX2 also results in anophthalmia/microphthalmia or coloboma, sometimes accompanied by systemic anomalies including pituitary defects in particular.
Heterozygous deletions/mutations in this homeodomain transcription factor are typically associated with Axenfeld-Rieger syndrome with ocular (anterior segment dysgenesis), dental (small or missing teeth), and umbilical anomalies (umbilical hernia, redundant periumbilical skin).
Another homeodomain transcription factor, heterozygous mutations in this gene have been reported in anterior segment dysgenesis and congenital cataract. A homozygous mutation was reported in one patient with microphthalmia and sclerocornea.
Heterozygous deletion/mutation of SOX2 results in anophthalmia/microphthalmia, often in combination with systemic anomalies including brain, pituitary, gastrointestinal, poor growth, genitourinary, and muscle anomalies. Mutations in SOX2 explain 15-20% of anophthalmia/microphthalmia.
Homozygous mutations in this homeodomain containing transcription factor results in isolated microphthalmia with or without coloboma and other ocular defects.
Anterior segment dysgenesis (ASD)
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
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.
How do I enroll a patient?
For more information about enrolling in this study, please contact Linda Reis at (414) 955-7645 or email@example.com.
Do I need to enroll family members?
Family participation (especially parents, even if unaffected) is encouraged as it makes interpretation of results much easier, but we will accept a patient without family members.
What type of samples do you accept?
We prefer blood or DNA samples, but can accept buccal swabs if necessary. For blood, please provide 10 cc (or 1cc/kg in infants) in EDTA (purple top). For DNA, please provide at least 5 ug. For buccal samples, please contact us for buccal swabs.
Where do I send the sample?
Ship sample Monday through Thursday only at room temperature via FedEx Overnight following standard procedures for shipping blood. If blood must be drawn on a Friday, please refrigerate the sample over the weekend and ship Monday morning for Tuesday delivery.
Ship blood sample and paperwork together to:
Medical College of Wisconsin
Translational and Biomedical Research Center
8701 Watertown Plank Road
Milwaukee, WI 53226
Do you pay for shipping?
Yes. Please contact us to obtain our FedEx number to cover shipping costs.
Will I get results?
We will inform you if a causative mutation is identified. As a research lab, we are not able to issue a formal mutation report. The mutation must be confirmed in a clinical (CLIA certified) laboratory; the clinical lab will then issue a mutation report which can be included in the medical record and used for testing family members. We will work with any clinical laboratory of your choice to arrange mutation confirmation.
How long before I get results?
The analysis is research-based and therefore is free, but results are not guaranteed. Initial results are typically available within one (1) year.
How much does the testing cost?
The analysis is research-based and therefore is free; there are no charges associated. If you opt to obtain clinical confirmation, the charge will be determined by the laboratory you select for testing.
What if no mutation is found?
We are working to identify other genes involved in eye disorders as well. Submitted samples will continue to be screened as new genes are identified until a mutation(s) is found (or no sample is left, whichever comes first).
How do I share information about this study with my family members?
There are two options. You can provide your family member with the contact information for Linda Reis, study coordinator at (414) 955-7645 or firstname.lastname@example.org or share the following invitation letter (PDF) with family members. It describes the study and provides an option for individuals to request more information about the study.
Participants can be accepted into this study from throughout the United States. Enrollment can be completed in person or via phone/mail. For more information about enrolling in this study, please contact Linda Reis at (414) 955-7645 or email@example.com.
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Here's what other families have to say:
"We are very happy because we can understand what is the exact problem..."
Parent of child with congenital glaucoma and mutations in CYP1B1.
"Studies like these are vital to affected children's health and for family planning. Keep up the amazing research."
Mother of child with Peters' plus syndrome and mutations in B3GALTL.
"Having a confirmed diagnosis has been wonderful, I can say this is what my child has and this is how we can help him."
Mother of child with syndromic microphthalmia and mutation in SOX2.
"The nagging worry that something may be seriously wrong and just was not identified yet is gone... The diagnosis has allowed me to move past the guilt. I have a new outlook on life… Our family and especially me are so thankful for the amazing work that is being done in your lab."
Parent of a child with syndromic microphthalmia.