Cornelia de Lange syndrome (CdLS) is a genetic condition characterised by certain distinct facial features, developmental delay, intellectual disability, certain behavioural attributes, and abnormalities in the upper limbs such as arms and hands.^1,2 It is a condition that affects multiple body systems (multisystem condition). Symptoms of CdLS range widely – classic CdLS describes severe and typical symptoms, and non-classic CdLS describes milder symptoms.^3,4 CdLS is usually recognisable from birth, and both males and females can be affected.¹ CdLS has been found to be caused by genetic variants in certain genes involved in the cohesin complex, which is crucial for the structure and function of chromosomes and gene expression.^1,2 There may also be other genes that are not yet identified.

Synonyms: CdLS, Brachmann-de Lange syndrome, BDLS.^3,4

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

ORPHA: 199 Cornelia de Lange syndrome 

ICD-11: LD2F.1Y Other specified syndromes with multiple structural anomalies, not of environmental origin 

Symptoms and severity of CdLS varies widely between individuals.¹  

Some of the common signs and features of CdLS include:^1-4 

• distinct facial features such as small head size (microcephaly), unibrow (synophrys), thick or well-arched eyebrows, long eyelashes, short nose, upturned nose (nasal) tip, inwards curvature/sunken appearance of the upper part of the nose (concave nasal ridge), groove between the nose and upper lip is longer than usual and not clearly defined (long indistinct philtrum), thin upper lip, downturned corners of the mouth 
• hirsutism (excessive hair growth following a male pattern of body hair in females) and/or hypertrichosis (excessive hair growth on anywhere of the body)  
• intellectual disability ranging from mild to severe 
• global developmental delay 
• feeding difficulties and failure to thrive 
• dental problems 
• hearing loss 
• gastro-oesophageal reflux disease
• limb malformations such as curvature of fingers (clinodactyly), small hands or feet, absence of one or more fingers (oligodactyly) and/or absence of all fingers (adactyly) 
• certain cognitive and behavioural attributes such as difficulties in sensory processing, impaired adaptive behaviour, repetitive behaviour, autism spectrum disorder, anxiety and mood disorders, self-injury behaviour which can be a sign of or response to pain 

Other organs such as eyes, heart, kidneys, musculoskeletal, nervous system, and the urinary and reproductive organs (genitourinary) may also be affected.^1-3

Please speak to your medical team to learn more about the symptoms and complications of CdLS. 

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

CdLS is a genetic condition. It is caused by disease-causing genetic changes (variants) in genes involved in the cohesin complex, which is crucial for the structure and function of chromosomes and gene expression.^1,2

The affected genes that have been identified so far are NIPBL (most common), SMC1A, HDAC8, SMC3, RAD21, BRD4, ANKRD11.¹ There may also be other genes that are not yet identified. 

For most individuals with CdLS, their genetic variant occurs randomly (de novo) prior to birth.^1,2 In some cases, the genetic variants are passed down (inherited) from their parents in either an autosomal dominant or X-linked manner. More information on these inheritance patterns can be found at: 

• Centre for Genetics Education: Autosomal dominant inheritance
• Centre for Genetics Education: X-linked inheritance

There has been reports of somatic mosaicism in some individuals, which means that the genetic variant is found in some but not all of their cells.⁵ More information about mosaicism can be found at Centre of Genetics Education: Mosaicism. 

If you would like to learn more about the inheritance and impact of this condition, please ask your doctor for a referral to a genetic counsellor. Genetic counsellors are qualified allied health professionals who can provide information and support regarding genetic conditions and testing. More information about genetic counselling can be found at: 

• Information on Genetic Services 
• The National and State Services pages underneath the ‘Genetic Counselling’ sections listed 

Diagnosis of CdLS may be made based on characteristic clinical features, and confirmed by genetic testing.¹

Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement (2018) developed by a group of international experts outlines recommendations on clinical diagnostic criteria for classic and non-classic CdLS phenotypes. 

CdLS may sometimes be detected before birth through pregnancy ultrasound tests.^1,3 Ultrasound tests may reveal features suggestive of CdLS, such as intrauterine growth restrictions (when the developing baby is smaller than expected), abnormalities in the limbs, facial structure or development and heart (cardiac), or diaphragmatic hernia (where there is an opening in the diaphragm muscle allowing abdominal organs to move up into the chest space). Further tests are usually needed to confirm the diagnosis. 

A differential diagnosis can rule out other conditions that have similar symptoms, such as CHOPS syndrome, KBG syndrome, Bohring-Opitz syndrome, Rubinstein-Taybi syndrome, X-linked syndromic intellectual developmental disorder-33, Alazami-Yuan syndrome, chromosome 2q31.1 duplication syndrome, Fryns syndrome and fetal alcohol syndrome.³ 

Please speak to your medical team to learn more about the available diagnostic pathways for CdLS. 

There is currently no curative treatment for CdLS. Treatment is targeted at managing symptoms (symptomatic management) and involves a multidisciplinary care team. This may include feeding therapy, use of hearing aids, physiotherapy, occupational therapy, speech therapy, special education, behavioural interventions, surgical interventions, as well as management of gastro-esophageal reflux disease, seizures and other affected organs.³

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities.

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

Healthcare professionals involved in the treatment of acromegaly may include general practitioners (GP), paediatrician, gastroenterologists, ophthalmologists, ear, nose and throat (ENT) specialists, audiologists, cardiologists, neurologists, psychiatrists, orthopaedists, urologists, immunologists, clinical geneticists, dietitians, dentists, physiotherapists, occupational therapists, speech pathologists.^1,3 The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here. 

We are not aware of any clinical care guidelines for CdLS in Australia. If you know of any relevant care guidelines, please let us know via the Contribute page. 

The following guidance is available from international experts outside Australia; however, there may be information that is not relevant or applicable to the Australian context, and may not be up to date: 

• Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement was developed by a group of international experts from 10 countries; published in 2018. 

• OrphanetAnesthesia : Anaesthesia recommendations for Cornelia de Lange syndrome; last modified in 2016. 

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

OrphanetAnesthesia has anaesthesia recommendations for Cornelia de Lange syndrome which focuses on airway management and prevention of aspiration – please note this was last modified in 2016 and may not be up to date. 

There are specific considerations around participating in rare disease research, including clinical trials. It is important to be mindful of issues such as data privacy, research ethics, consent and differences in research regulations between Australia and other countries.

If you are interested in finding clinical trials for your condition, please visit the following websites; however, there may not be any clinical trials available:

• Australian Clinical Trials
• ClinicalTrials.gov

It is best to discuss your interest in any clinical trials with your medical team to determine suitability and eligibility.

Please note that RVA does not necessarily monitor or endorse each group/organisation’s operational governance and activities.

Australian Organisation:

Cornelia de Lange Syndrome Association Australasia
Website: https://www.cdls.org.au/ 

Please note that RVA does not monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

CdLS vary between individuals, and each person’s experience is unique.  

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.

People living with a rare disease, including families and carers, often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many people find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful. Information about relevant mental health and wellbeing support can be found at:

• Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

Further information on CdLS can be found at: 

• Genetic and Rare Diseases (GARD) Information Center: Cornelia de Lange Syndrome 
• National Organization for Rare Disorders (NORD): Cornelia de Lange Syndrome 

• GeneReviews^®: Cornelia de Lange Syndrome 
• Online Mendelian Inheritance in Man, OMIM^®: #122470 Cornelia De Lange Syndrome 1; CDLS1 
• Online Mendelian Inheritance in Man, OMIM^®: #300590 Cornelia De Lange Syndrome 2; CDLS2 
• Online Mendelian Inheritance in Man,OMIM^®: #610759 Cornelia De Lange Syndrome 3 with or without midline brain defects; CDLS3 
• Online Mendelian Inheritance in Man, OMIM^®: #614701 Cornelia De Lange Syndrome 4 with or without midline brain defects; CDLS4 
• Online Mendelian Inheritance in Man, OMIM^®: #300882 Cornelia De Lange Syndrome 5; CDLS5 
• ORPHA:199 Cornelia de Lange syndrome 

This page has been developed by Rare Voices Australia (RVA)’s RARE Portal team.

If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.