Lenz microphthalmia syndrome (LMS) is an X-linked disorder characterized by unilateral or bilateral microphthalmia and/or anophthalmia. Extraocular malformations may affect the ears, teeth, fingers, skeleton, and genitourinary system. Other features can include glaucoma, coloboma, hearing loss, microcephaly, webbed neck, and cleft lip/palate. Developmental delay or intellectual disability is present in approximately 60% of affected males. BCOR is the only gene known to be associated with LMS although another X-linked locus is also known to be associated. Female carriers are typically not affected.
Oculofaciocardiodental (OFCD) syndrome (OMIM #300166) is also associated with mutations in BCOR. OFCD syndrome affects females and is lethal in males. Characteristics include congenital cataracts with or without unilateral/bilateral microphthalmia, long narrow face, cleft palate, cardiac defects, and dental anomalies. Microphthalmia is less severe in OFCD syndrome than in LMS. Females with OFCD syndrome often have normal intelligence. Known BCOR mutations causing OFCD include point mutations, small deletions, and deletions involving one or more exons.
For patients with suspected BCOR-related disorders, sequence analysis is recommended as the first step in mutation identification. For patients in whom mutations are not identified by full gene sequencing, deletion/duplication analysis is appropriate.
- Confirmation of a clinical diagnosis of a BCOR-related disorder in an individual in whom sequence analysis was negative.
- Carrier testing in adults with a family history of a BCOR-related disorder in whom sequence analysis was negative.
Please note that a "backbone" of probes across the entire genome are included on the array for analytical and quality control purposes. Rarely, off-target copy number variants causative of disease may be identified that may or may not be related to the patient's phenotype. Only known pathogenic off-target copy number variants will be reported. Off-target copy number variants of unknown clinical significance will not be reported.
Submit only 1 of the following specimen types
Preferred specimen type: Whole Blood
Type: Whole Blood
Specimen Requirements:In EDTA (purple top) or ACD (yellow top) tube:
Infants (<2 years): 2-3 ml
Children (>2 years): 3-5 ml
Older Children & Adults: 5-10 ml
Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.
Specimen Requirements:OrageneTM Saliva Collection kit (available through EGL) used according to manufacturer instructions.
Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.
- Sequence analysis of the BCOR gene is available and is required before deletion/duplication analysis.
- Custom diagnostic mutation analysis (KM) is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.
- Prenatal testing is available only for known familial mutations to individuals who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.
- X-Linked Intellectual Disability panels are available for 30, 60, and 90 genes.