Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement

Abstract

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning.

Missense variants in TAF1 and developmental phenotypes: Challenges of determining pathogenicity

“…Individual 13 had been given a clinical diagnosis of Cornelia de Lange syndrome (CdLS), which is based on the presence of craniofacial features, growth failure, ID, and limb malformations/anomalies, which include the classical preaxial hand oligodactyly/radial ray/upper limb anomaly. According to the recently published international consensus statement on CdLS diagnosis and management (Kline et al, ), he does meet the criteria for nonclassic CdLS, as he has an overall score of 10 points: synophrys, mild (2 points), short nose and upturned nasal tip (2 points), long, smooth philtrum (2 points), possibly downturned corners of mouth (2 points), global DDs (1 point), and microcephaly (1 point). In the prior cohort paper, Individual 4A had also been given a clinical diagnosis of CdLS (O'Rawe et al, ), and Individual 4 in this current cohort has brachydactyly (Table ).…”

Chromatinopathies: A focus on Cornelia de Lange syndrome

“…Cornelia de Lange syndrome (CdLS, OMIM #122470, #300590, #610759, #614701, #300882) is a rare and clinically variable syndrome manifesting with developmental disability, growth impairment, multi‐organ abnormalities (including limb anomalies, congenital heart defects, gastrointestinal dysfunction and neurodevelopmental alterations) and typical facial dysmorphisms (such as hirsute forehead, arched eyebrows with synophrys, short nose with depressed nasal bridge, anteverted nares, long and smooth philtrum, thin lips, downwards turning corners of the mouth) . According to the recently published international consensus statement, “CdLS‐spectrum” includes the classical and non‐classical phenotype caused by pathogenic variants in genes encoding the cohesin complex and its interactors …”

Cornelia de lange manifestations in otolaryngology: A systematic review and meta‐analysis

“…Most patients have synophrys; long, thick eyelashes; small anteverted nares; micrognathia; and cleft or high‐arched palate . Hearing loss is also extremely common in these patients due to external, middle, and inner ear anomalies . Although these manifestations are among the most common ones reported, limited information is published regarding the prevalence of each.…”

“…Although these manifestations are among the most common ones reported, limited information is published regarding the prevalence of each. Due to the complexity of this disorder, the first international consensus statement was recently published . However, due to the breadth of included recommendations, it provides only a limited review of otolaryngology manifestations and is not designed to be a comprehensive, systematic review of the literature.…”