Two Siblings with a Mutation in CCDC8 Presenting with Mild Short Stature: A Case of 3-M Syndrome.

Background: Short stature can be caused by mutations in a multitude of different genes. 3-M syndrome is a rare growth disorder marked by severe pre- and postnatal growth retardation along with subtle dysmorphic features. There have only been 2 prior reports of mutations in CCDC8 causing 3-M syndrome.

Methods: Two patients presenting with mild short stature underwent whole exome sequencing. The mutation was confirmed via Sanger sequencing. We compare the clinical characteristics of our 2 patients to patients previously reported with mutations in the same gene.

Results: Exome sequencing identified a homozygous frameshift mutation in CCDC8 in both patients. They presented with a much milder phenotype than previously described patients with the same mutation.

Conclusion: In this study, we report a case of 2 sisters with relatively mild short stature who were found via exome sequencing to carry a previously reported homozygous mutation in CCDC8. These patients expand the anthropometric phenotype of 3-M syndrome and demonstrate the power of exome sequencing in the diagnosis of children with short stature. 3-M syndrome should be considered in children with mild skeletal abnormalities, normal/high growth hormone-IGF axis parameters, and normal intelligence.