OMIM ID:
CODAS Syndrome
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Dense nuclear cataracts can be seen by six months of age. Some patients have ptosis. The fundi have been described as normal at one month of age in a single infant but vision was described at the 20/200 level at 2 years of age. Cataracts noted at 4 months had been removed.
Systemic Features
Patients have multiple severe systemic abnormalities. There is generalized developmental delay along with mild microcephaly and hypotonia. The forehead is often broad while the face appears flattened with anteverted nares, a flat nasal bridge, a short philtrum, low-set and crumpled ears. Infants may have an inadequate upper respiratory apparatus with atrophic vocal cords and some die of laryngeal obstruction in the first days of life. Sialorrhea and difficulty swallowing have been noted. Mild to moderate neurosensory hearing loss is often present but there may also be a conduction component to this.
Brain imaging has revealed large ventricles, with subcortical hypomyelination, a thin corpus callosum, and prominent cortical sulci. The vertebrae may have coronal clefts and scoliosis often develops. Generalized metaphyseal dysplasia and delayed bone age are usually present. The anus may be imperforate and a rectovaginal fistula and cryptorchidism have been reported. Long bones may be malformed as well and most patients are short in stature. Delayed dentition, enamel dysplasia, and abnormal cusp morphology are often present. Cardiac septal defects may be seen.
Genetics
Inheritance
Homozygous mutations in LONF1 (19p13.3) segregate with the 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.