This study will try to learn more about the genetic cause and symptoms of microphthalmia
(small eyes) or anophthalmia (absence of one or both eyes).
Patients with microphthalmia or anophthalmia with mental retardation may be eligible for
this study. Patients' parents and siblings will also be included for genetic studies.
Patients may participate in both the clinical and laboratory parts of the study or just the
laboratory part, as described below:
The laboratory study consists of DNA analysis to determine the genetic cause of
microphthalmia/anophthalmia. The DNA sample is obtained using one of the following methods:
- Blood draw - for young children, a numbing cream is applied to the skin before the
needlestick to decrease the pain
- Skin biopsy - a small piece of skin (about 1/8-inch in diameter) is removed surgically
after the area has been numbed with an anesthetic
- Cotton swab - a specimen is collected from inside the cheek using a cotton swab. This
is done only for patients who cannot provide a blood or skin sample.
- Prenatal sample - If, in the case of newborns, specimens are left from prenatal
testing, these can be used instead of a blood sample.
Some patients may have a permanent cell line grown from the blood or skin sample for use in
future research tests.
For the clinical study, participants undergo some or all of the following procedures at the
NIH Clinical Center:
- Physical examination
- Clinical photographs, X-rays, blood tests
- Magnetic resonance imaging (MRI) scan of the brain - a diagnostic procedure that uses a
magnetic field and radio waves instead of X-rays to produce images of the brain
We propose to identify and analyze the underlying mechanistic pathway of X-linked
microphthalmia/anophthalmia. This is a heterogeneous group that includes syndromic
microphthalmia 1 (MCOPS1) OMIM #309800, and syndromic microphthalmia 2 (MCOPS2) OMIM #300166
and other, as yet to be defined, malformations of the globe. We have identified a causative
gene for MCOPS1 (Ng, et al 2004). To further delineate these conditions, we will study
families with these features through a combined clinical and molecular approach. Specimens
will be collected and evaluated in the laboratory by linkage analysis, physical mapping,
candidate gene characterization, mutation screening, genotype-phenotype correlation, and
cell biologic studies of normal and mutant proteins.
- INCLUSION CRITERIA:
Inclusion criteria will consist of affected individuals with unilateral or bilateral
microphthalmia/anophthalmia from families with an X-linked mode of transmission. In
addition, we may analyze patients with mental retardation with or without eye defects to
allow genotype phenotype correlation studies. Parents and siblings will be included for
linkage analysis. Unaffected non-transmitting parents may be included to clarify haplotype
status. In addition, families with X-linked microphthalmia/anophthalmia with associated
anomalies such as Lenz dysplasia and other X-linked microphthalmia/anophthalmia syndromes
will be analyzed to determine if these conditions are allelic. Sporadic cases of
microphthalmia with or without mental retardation may be considered for study, along with
parents and unaffected siblings. Unaffected subjects may also be enrolled if needed for
Specimens from patients collected at outside institutions may be accepted into the study
if they were collected under an IRB-approved protocol at a multiple project assurance
(FWA) institution or if the IRB waives review of the study and allows usage of the NIH
consent. Some of these patient samples may represent overlapping phenotypes (e.g.,
laterality defects) and not microphthalmia. Inheritance patterns may not be known for
If the patient has microphthalmia/anophthalmia with autosomal recessive, autosomal
dominant pattern of inheritance, the family will be excluded. While this criterion should
enrich for X-linked syndromic microphthalmia, the rarity of the disorder necessitates that
we will accept small families and even sporadic cases if they have substantial clinical
overlap with Lenz or OFCD.