OMIM ID:
GAPO Syndrome
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Progressive optic atrophy is considered part of this syndrome but it is not a consistent feature. One patient with the suspected diagnosis had papilledema while other individuals may have congenital glaucoma, buphthalmos, band keratopathy, and keratoconus. White eyelashes have been described. Myelinated nerve retinal nerve fibers may be prominent.
Systemic Features
This is a rare congenital disorder with so far incomplete phenotypic delineation. The diagnosis can be made soon after birth from the general facial and body morphology. The dysmorphism is secondary to marked bone growth retardation and metaphyseal dysplasia, resulting in a flat midface, frontal bossing, micrognathism, chest deformities, and vertebral anomalies. Psychomotor retardation is common but the extent of cognitive deficits is unknown. The permanent teeth may begin to develop but fail to erupt (pseudoanodontia). Even primary dentition is often abnormal. Alopecia is a feature although some individuals do have sparse body hair, at least for a period of time. Anomalous blood vessels such as dilated scalp veins are sometimes evident. Hypogonadism has been reported in both sexes. Individuals are subject to recurrent ear and respiratory infections.
Genetics
Inheritance
GAPO occurs in both sexes. Homozygous mutations in the ANTXR1 gene (2p13.3) are responsible for this disorder.
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.