ClinVar

Description

This 9 year old female has severe intellectual disability, growth and feeding problems requiring a G-tube as an infant, a repaired cleft palate, short stature (4 SD below average), microcephaly, scoliosis, deviated septum, widely set nipples, curved 4th and 5th digits bilaterally, recurrent nosebleeds, and possible hearing loss. Dysmorphic facial features include midface depression, prominent forehead, low set and posteriorly rotated ears, and micrognathia. Benign pulmonary artery branch stenosis and a small PFO were noted on echocardiogram, and an abnormal brain MRI done at 8 years of age showed scattered, non-enhancing, non-specific punctate predominately subcortical T2 hyperintensities with mild-moderate cerebral volume loss. Her bone age at 8 years, 1 month was essentially normal (0.3 SD below mean). Tympanograms were done at 7 years of age and were within normal limits bilaterally with OAEs at fail/refer results bilaterally. The p.G297S variant was maternally inherited and is present in gnomAD, occurring 0.01% in the Latino population and 0.02% in European non-Finnish. Computational model predictions are inconsistent. A second VUS was also identified in COLL11A2, inheritance is unknown.