Objective  To investigate the clinical phenotypes and genotypic characteristics of Chinese patients with Coffin-Lowry syndrome.

Methods  The clinical data and genetic test results of a family with Coffin-Lowry syndrome were retrospectively analyzed. A literature review was conducted to summarize the clinical characteristics and gene mutation characteristics of patients with Coffin-Lowry syndrome in China.

Results  The proband was a 1-year-old boy with distinctive facial features, puffy but tapered fingers, hypotonia, growth retardation, and delayed cognitive and motor development. Genetic analysis revealed a hemizygous c.1603-2A>G mutation in intron 17 of the RPS6KA3 gene in the proband. His mother was a heterozygous carrier. The identified mutation has not been reported previously. The proband′s maternal half-brother and half-sister also exhibited similar clinical manifestations and were diagnosed with Coffin–Lowry syndrome together with the proband. The proband was followed up until 3 years and 8 months old, by which time he was not capable of walking steadily independently or speech. Including the 4 members of this family, a total of 28 Chinese patients were identified. Their clinical manifestations included special facial features (100%), cognitive and language/motor developmental delays (92.6%), hypotonia (95.2%), tapered fingers (88.5%), and scoliosis or kyphosis (45%). Genetic sequencing was performed in 24 patients, revealing missense mutations in 3 cases (12.5%), frameshift mutations in 5 cases (20.8%), nonsense mutations in 9 cases (37.5%), splice-site mutations in 4 cases (16.7%), and exon deletions in 2 cases (8.3%). No mutation hotspots were identified.

Conclusion Coffin-Lowry syndrome should be considered in children with cognitive and language/motor developmental delays, distinctive facial features, tapered fingers, and hypotonia. Genetic testing can assist with early diagnosis.