Patients with Cornelia de Lange syndrome (CdLS) [OMIM #122470] have characteristic facial features, growth retardation, hirsutism, and upper limb reduction defects. More than 95% of patients with CdLS have limb involvement, but only 25% have severe limb anomalies. Characteristic facial features include synophrys, long eyelashes, depressed nasal bridge with an uptilted nasal tip and anteverted nares, thin upper lip with downturned corners of the mouth, and posteriorly rotated low-set ears. Most individuals have severe to profound mental retardation, but more mild cognitive delays have been reported.
A small, in-frame deletion of the SMC3 gene [OMIM #606062] gene has been reported in a patient with atypical facial characteristics and absent limb anomalies. Mutations of the RAD21 [OMIM #606462] gene have been reported in 1% or less of CdLS patients. Missense mutations and whole gene deletions have been identified in the RAD21 gene. Mutations of the HDAC8 [OMIM #300269] gene have been identified in 5/154 (3%) individuals with CdLS that were negative for mutations in NIPBL, SMC1A, SMC3 and RAD21.
Our Tier 3 test for Cornelia de Lange syndrome is mutation analysis of all coding exons and intron/exon boundaries of SMC3, RAD21 and HDAC8 gene by direct sequencing of amplification products in both the forward and reverse directions.
Contact the Cornelia de Lange Syndrome Foundation (www.cdlsusa.org) for more information and support.