A syndrome combining multiple malformations involving head and skeleton. CODAS is an acronym that stands for Cerebral Ocular Dental Auricular Skeletal anomalies.
Around 12 cases have been reported.
Autosomal recessive, but several sporadic cases have also been reported. Initially this syndrome is described in two girls and one boy, two of them of Mennonite ancestry. Consanguinity was not reported in any of the cases. Recent research in the cause of the disorder points to mutations in LONP1 (Mitochondrial LON Peptidase 1) gene located on chromosome 19p13.3, which encodes a multifunctional mitochondrial adenosine triphosphate (ATP)-dependent protease and is diverse roles, including elimination of misfolded or damaged proteins, chaperone-like assembly of respiratory chain protein complexes, and regulation of mitochondrial gene expression.
Based on the clinical findings.
Laboratory investigations such as karyotype, metabolic screening, and studies of cholesterol biosynthesis and peroxisomes all yield normal results. Head and neck anomalies may include microcephaly, broad forehead, alopecia, thin eyebrows, overfolded (“crumpled”) ears with dysplastic helices, flat midface with flat nose and vertically grooved nasal tip, short philtrum, abnormal enamel projections, and gingiva hypertrophy. Eye anomalies such as congenital cataracts (present in all patients), ptosis, and nystagmus and conductive and/or sensorineural hearing loss may be present. Brain MRI-scanning in one patient revealed symmetric ventriculomegaly, mild diffuse cortical atrophy, prominent cortical sulci, subcortical hypomyelination, and hypoplasia of the corpus callosum, while in another patient it showed progressive atrophy of the cerebellar cortex and caudate nucleus. Developmental delay may be present; however, recent reports highlight the importance of treating visual and hearing impairment early on as this can alleviate developmental delay significantly. Cardiac defects are common (atrial/ventricular septal defects, atrioventricular canal), and pulmonary hypertension in combination with a ventricular septal defect has been described in one patient. Possible skeletal and muscular abnormalities consist of short stature, delayed ossification of upper and lower extremities, epi- and metaphyseal dysplasia, odontoid hypoplasia, in one case with odontoid synostosis, deformed vertebral bodies with coronal clefts, early and progressive scoliosis, radiologic signs of spondyloepiphyseal dysplasia, generalized abnormalities of the ilium, genua valga, joint dislocations, hypoplastic pectoral muscles, generalized hypotonia, restricted pronation and supination, and motor delay. Other anomalies that have been reported include omphalocele, imperforate anus, rectovaginal fistula, hemiatrophy of the tongue, and cholestasis due to extrahepatic bile duct atresia. A high percentage of these patients require intubation and/or tracheostomy for respiratory failure/airway obstruction due to vocal cord paresis and atrophy, and glottic narrowing. In one report, three patients died from laryngeal obstruction in the neonatal period, and one with a tracheostomy died in early infancy from pneumonia. Four children required tracheostomies to survive infancy. Swallowing dysfunction is common and some children are entirely fed by gastrostomy tube.