Microphthalmia and Anophthalmia, ALDH1A3 Associated
Defective Genes
Clinical Characteristics
Ocular Features
Patients have a variety of ocular malformations including microphthalmia and clinical anophthalmia. Some have orbital cysts. Imaging may reveal hypoplastic optic nerves and chiasms.
Systemic Features
Both cardiac (pulmonary stenosis and septal defects) and neurological deficits (autism spectrum disorders and 'intellectual disability') have been reported. Birth weight and head circumference are often low. However, brain imaging has revealed no consistent malformations.
Genetics
Inheritance
This is an autosomal recessive disorder resulting from homozygous mutations in the gene ALDH1A3 (15q26.3) which encodes the enzyme retinaldehyde dehydrogenase. Mutations in ALDH1A3 impair the enzymatic oxidation of retinaldehyde important to the synthesis of retinoic acid, a key signaling molecule in eye development.
However, mutations in other genes important to ocular development such as GJA3 and SOX2 (a transcription factor) may result in a similar phenotype.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.