CODAS Syndrome

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.


Homozygous mutations in LONF1 (19p13.3) segregate with the phenotype.

Autosomal recessive
Treatment Options: 

There is no general treatment available and infants sometimes die from laryngeal obstruction in the first days of life.   Individual anomalies may be surgically correctable in selected individuals.  Occasional infants are stillborn but one patient died an accidental death at 14 years of age. 

Article Title: 

CODAS syndrome is associated with mutations of LONP1, encoding mitochondrial AAA+ Lon protease

Strauss KA, Jinks RN, Puffenberger EG, Venkatesh S, Singh K, Cheng I, Mikita N, Thilagavathi J, Lee J, Sarafianos S, Benkert A, Koehler A, Zhu A, Trovillion V, McGlincy M, Morlet T, Deardorff M, Innes AM, Prasad C, Chudley AE, Lee IN, Suzuki CK. CODAS syndrome is associated with mutations of LONP1, encoding mitochondrial AAA+ Lon protease. Am J Hum Genet. 2015 Jan 8;96(1):121-35.

PubMed ID: 
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