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Cornelia De Lange Syndrome


Children with Cornelia de Lange syndrome often present with unusual facial features that develop within a few weeks to months after birth. There is slowed growth combined with development of several other abnormalities which have been described below:

  • Extensive clinical evaluation and WES of 32 Turkish patients clinically diagnosed with CdLS revealed the presence of a de novo heterozygous nonsense KMT2A mutation in 1 patient without characteristic WDSTS features.[ncbi.nlm.nih.gov]
Unilateral Ptosis
  • Won Jae Kim, Surgical treatment of esotropia and unilateral ptosis in a patient with Cornelia de Lange syndrome, Yeungnam University Journal of Medicine, 10.12701/yujm.2019.00066, 36, 2, (152-154), (2019).[doi.org]


No single test can diagnose CdLS. A thorough physical examination would be done to carefully study for the signs and symptoms of the disease. In addition, X-ray and genetic testing are carried out to figure out the genetic mutations.

Imaging studies such as CT scan of the temporal bone need to be done to determine any abnormalities in the middle and inner ear. Hearing conduction tests must also be conducted because 90% of CdLS patients have an associated hearing disorder [10].

Ultrasound of the renal tract is also a necessity to understand abnormalities associated with the renal system. Echocardiography is also indicated in patients with CdLS to determine the cardiac functioning.


The major goal of treatment of CdLS is management of the symptoms to reduce discomfort associated with secondary anomalies. Treatment approach varies with age of the patient as the special needs of the child need to be catered to. This further means that a combined approach for correcting physical development and cognitive skills needs to be carried out.
Children with CdLS also suffer from various other associated disease conditions. Therefore appropriate treatment for each disease condition is also carried out.


Prognosis of the disease is usually unfavorable as affected children experience severe morbidity. Majority of the children die during the first few years of life. Those who survive these years have a short life span [5]. Retrospective reviews on CdLS patients shows that respiratory symptoms are the major cause of death [6].


Complications of CdLS include the following:


The major factor that is known to play foul in the causation of Cornelia de Lange syndrome is genetic mutations [2]. A total of 4 genes were found to be responsible for causing the congenital disorder.

Out of the 4 genes, the most common genetic mutation that gives rises to 50% cases of CdLS is the NIPBL gene on the chromosome 5. Gene SMC1A on the chromosome X and gene SMC3 on the chromosome 10 account for rest of the cases [3]. The fourth gene known as HDAC8 on chromosome was discovered in the year 2012; however there is little evidence about the association of the gene with CdLS.

CdLS is not a heredity disorder and there are rare cases to prove that individuals living with such a syndrome would have children of their own.


The exact incidence of CdLS is not known. However, with the available data it can be concluded that 1 in every 10,000 to 30,000 develops CdLS.

Sex distribution
Age distribution


Cornelia de Lange syndrome is a genetic disorder arising from mutation of multiple genes. During the early developmental years, mutations of the genes NIPBL, SMC1A, SMC3 and HDAC8 are known to trigger series of events that send across faulty information giving rise to unusual facial features, developmental delay, and underdeveloped upper extremities and feeding problems [4]. Researchers have pointed towards the fact that 99% cases of CdLS are sporadic in nature.


Many cases of the disease can be prevented using prenatal diagnostic testing. Ultrasound examination during pregnancy can show intrauterine growth retardation. However, studies showed that about 68% of the cases of CdLS were not detected by this method. Therefore, proper examination during the second trimester for detection of few typical characteristics such as cystic hygroma, diaphragmatic hernia and right hand with 3 rays can provide information about CdLS. In addition, maternal serum testing for pregnancy associated plasma protein during the second trimester can also help in detecting CdLS.


Cornelia de Lange syndrome, abbreviated as CdLS is a congenital disorder causing developmental delay in children. This disorder is typically not diagnosed at birth and presents with severe physical and mental challenges.

CdLS was first described in the year 1933 by the scientist Cornelia de Lange [1]. However, Brachmann also described characteristics similar to this disorder in the year 1916. Cornelia de Lange syndrome is characterized by behavioral problems, developmental delay, distinctive facial features, malformed upper extremities and growth deficiency. Genetic mutations are the major factor that gives rise to development of CdLS.

Patient Information


Cornelia de Lange syndrome (CdLS) is a congenital disorder characterized by slowed growth, poor development and unusual distinct facial features in affected children. Such a type of syndrome occurs due to genetic mutations. Affected children have a poor life expectancy as they are unable to survive the various associated disease conditions they suffer from. Children with CdLS also suffer from behavioral problems and have delayed cognitive development.


Cornelia de Lange syndrome occurs due to genetic mutations of 4 genes namely NIPBL, SMC1A, SMC3 and HDAC8. Researchers have also pointed towards the fact that about 99% cases of CdLS are sporadic in nature.


Children with CdLS are born with distinct facial features characterized by long eyelashes, thin lips, typically thick eyebrows that join at midline, low set ears and upturned nose. In addition, some of the other symptoms include presence of severe body hair, small head, small hands and feet, under developed upper extremities, vision impairment, hearing problems, seizures, feeding problems, heart abnormalities, hypoglastic genetalia and cleft palate.


Diagnosis of CdLS includes thorough physical examination of the signs and symptoms. In addition, genetic testing is carried out to study the genetic mutations. In addition, ultrasound of the renal tract and echocardiogram are necessary to study abnormalities of the kidneys and heart.


Treatment of CdLS includes management of the several disease conditions the child is suffering from. In addition, speech and behavioral therapy also forms a major part of the treatment regime.



  1. de Lange C. Sur un type nouveau de degeneration (typus amstelodamensis). Arch Med Enfants. 1933; 36:713-9.
  2. Huisman SA, Redeker EJ, Maas SM, Mannens MM, Hennekam RC. High rate of mosaicism in individuals with Cornelia de Lange syndrome. J Med Genet. May 2013; 50(5):339-44.
  3. Deardorff MA, Kaur M, Yaeger D, et al. Mutations in cohesin complex members SMC3 and SMC1A cause a mild variant of cornelia de Lange syndrome with predominant mental retardation. Am J Hum Genet. Mar 2007; 80(3):485-94.
  4. Wilmink FA, Papatsonis DN, Grijseels EW, Wessels MW. Cornelia de lange syndrome: a recognizable fetal phenotype. Fetal Diagn Ther. 2009; 26(1):50-3.
  5. Kline AD, Grados M, Sponseller P, Levy HP, Blagowidow N, Schoedel C, et al. Natural history of aging in Cornelia de Lange syndrome. Am J Med Genet C Semin Med Genet. Aug 15 2007; 145C (3):248-60.
  6. Schrier SA, Sherer I, Deardorff MA, Clark D, Audette L, Gillis L, et al. Causes of death and autopsy findings in a large study cohort of individuals with Cornelia de Lange syndrome and review of the literature. Am J Med Genet A. Dec 2011; 155A (12):3007-24.
  7. Kline AD, Krantz ID, Sommer A, et al. Cornelia de Lange syndrome: Clinical review, diagnostic and scoring systems, and anticipatory guidance Am J Med Genet Part A 143A:1287-1296. Am J Med Genet A. Sep 24 2008; 146A (20):2713.
  8. Moss J, Oliver C, Hall S, et al. The association between environmental events and self-injurious behaviour in Cornelia de Lange syndrome. J Intellect Disabil Res. 2005; 49:269-77.
  9. Sarimski K. Analysis of intentional communication in severely handicapped children with Cornelia-de-Lange syndrome. J Commun Disord. 2002; 35:483-500.
  10. Marchisio P, Selicorni A, Pignataro L, et al. Otitis media with effusion and hearing loss in children with Cornelia de Lange syndrome. Am J Med Genet A. Feb 15 2008; 146A (4):426-32.

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Last updated: 2019-07-11 20:26