Molecular genetic testing of RPS6KA3, the only gene known to be associated with CLS, can be used to confirm but not to rule out the diagnosis of CLS. Sequence analysis identifies mutations in about 35%-40% of probands. Dozens of mutations have been identified that can cause CLS characteristics. This makes a positive diagnosis using genetic testing very difficult. Professionals trained in genetic disorders and birth defects often can make the diagnosis after performing a physical exam and observing the child's behavior.
Tapering fingers, the most reliable diagnostic feature, may also be observed in other intellectual disability syndromes, including Borjeson syndrome (MIM# 301900) and Prader-Willi syndrome (MIM# 176270). [Delaunoy et al 2001]
Often a diagnosis comes after a developmental evaluation when a child appears to be delayed in reaching several developmental milestones. Parents should be prepared for the likelihood that even though a clinical diagnosis is made, they may not get a confirming positive genetic diagnosis.
For more information, see Genetic Testing - Your Questions Answered. Click here for more information on facilities that offer tests for Coffin-Lowry syndrome.