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Congenital primary aphakia
Disease definition
A rare developmental defect during embryogenesis characterised by an absence of the lens. CPAK can be associated with variable secondary ocular defects.
ORPHA:83461
Classification level: DisorderSummary
Epidemiology
Congenital primary aphakia (CPAK) prevalance is unknown.
Clinical description
CPAK is a congenital eye defect presenting at birth with no lens formation, resulting from a failure of lens induction from the surface ectoderm and aborted lens development. CPAK is often associated with other ocular anomalies, including aplasia/dysplasia of the anterior segment of the eye, microphthalmia, glaucoma.
Etiology
CPAK is caused by variants in the FOXE3 gene. Most cases are autosomal recessive. It is important to note that both dominant and recessive variants in FOXE3 are associated with a variable mixed phenotype of developmental eye disorders including anterior segment dysgenesis, microphthalmia, Peters anomaly, sclerocornea, early-onset cataract, glaucoma and ocular coloboma.
Diagnostic methods
Molecular diagnosis can be made through genetic testing, for example whole exome/genome sequencing and can be validated by bi-directional Sanger sequencing. Clinical diagnosis can be made based on clinical examination and confirmed with ultrasound. Anterior segment ultrasound biomicroscopy may aid detection of co-existent anterior segment dysgenesis. Due to the association of CPAK and the rubella virus, a TORCH complex evalutation is also recommended.
Antenatal diagnosis
Transabdominal ultrasound at 23 weeks gestation has detected CPAK.
Genetic counseling
Genetic testing for FOXE3 variants will provide a molecular diagnosis. This yields information regarding carrier status and provide choices that would not otherwise be available to facilitate decision making for the patient and their family. Genetic testing is essential for defining inheritance patterns, carrier status and enabling effective genetic counselling with consequent implications for prenatal or pre-implantation genetic diagnosis.
Management and treatment
CPAK should be managed by specialists with expertise in the condition. Supportive measures for those with sight impairment include involvement of social services. Regular follow-up will be required to monitor progression of associated anterior segment dysgenesis and glaucoma with medical and surgical interventions where needed. Intraocular surgery is not advised unless steps are taken to avoid inflammatory membrane formation and subsequent retinal detachment. Regular refraction to reduce/prevent amblyopia. Genetic counselling should be offered to the family.
Prognosis
Early diagnosis will enable prompt supportive treatment.
A summary on this disease is available in Italiano (2006) Deutsch (2020) Español (2020) Français (2020) Nederlands (2020) Russian (2020, pdf)
Detailed information
Genetic Testing
- Guidance for genetic testing
- English (2018, pdf) - Eur J Hum Genet
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