Cornelia de Lange, syndrome

[MIM 122 470300 590, 300 882610 759614 701]

(Brachmann-de Lange syndrome, Amsterdam dawrfism, Bushy syndrome)

Prevalence: 1/10,000 to 1/50,000. Malformative syndrome. Sporadic in most cases but an autosomal dominant transmission is sometimes observed:  

Depending on the gene involved, one distinguishes:

-        CDLS1 [MIM 122 470]: mutation of the NIPBL gene (5p13.2), accounting for 50-60 % of the cases

-         CDLS2 [MIM 300 590]: mutation of the SMC1A gene (Xp11.22-p11.21) (X-linked form),5 % of the cases

-         CDLS3 [MIM 610 759]: mutation of the SMC3 gene (10q25.2)

-        CDLS4 [MIM 614 701]: mutation of the RAD21 gene (8q24.11)

-        CDLS5 [MIM 300 882]: mutation of the HDAC8 gene (Xq13.1)


Most of these genes are part of the cohesin complex, which plays an important role in DNA duplication during meiosis, in the matching and repair of the DNA fibers, in the cohesion of the chromosomes and in the transcription of DNA into RNA.


Association of:

-         typical facial dysmorphism: arched, thick and confluent eyebrows [synophrys], thin lips,  anteverted nares, micrognathia

-         mental and growth retardation

-         limb anomalies: micromelia, clinodactyly, oligodactyly or brachydactyly

-         hirsutism

-         sometimes cardiac (pulmonary stenosis) and external genitalia malformations . 

Frequent severe gastroesophageal reflux. Tendency to self-harm. Autistic-like behavior.


Anesthetic implications: 

Difficult intubation; in 30% of cases, it is necessary to opt for an endotracheal tube with a smaller diameter than foreseen according to age. Gastroesophageal reflux. Difficult venous access. No risk of malignant hyperthermia on the contrary to what is suggested by Gene Reviews 2016.


References : 

-         Sargent WW. 
Anesthetic management of a patient with Cornelia de Lange syndrome. 
Anesthesiology 1991; 74:1162-3.

-         Munoz-Corsini L, De Stefano G, Porras MC, Galindo S, Palencia J. 
Anaesthetic implications of cornelia de Lange syndrome
Pediatr Anesth 1998 ; 8 : 159-61.

-        Papadimos TJ, Marco AP.
Cornelia de Lange syndrome, hyperthermia and a difficult airway.
Anaesthesia 2003; 58: 924-5

-         August DA, Sorhabi S.
Is a difficult airway always predicatable in Cornelia de Lange syndrome ? 
Pediatr Anesth 2009; 19: 707-8.  

-        Ingram B, Frost EAM.
Post-operative complications after palatoplasty in a 19 month old female with Cornelia de Lange syndrome.
MEJ Anesth 2011; 21: 419-21. 

-        Moretto A, Scaravilli V, Ciceri V, Bosatra M, Giannatelli F et al.
Sedation and general anesthesia for patients with Cornelia De Lange syndrome: a case series.
Am J Med Genet Part C 2016; 172C:222-8.

-         Emerson B, Nguyen T.
Are children with Cornelia de Lange syndrome at risk for malignant hyperthermia?
Pediatr Anesth 2017; 27: 215-6


Updated: April 2020