What Is Chanarin-Dorfman Syndrome?

  • Deepika Rana Bachelor of Dental Surgery(BDS), Dentistry , H.P.Government Dental College, IGMC Shimla.Himachal Pradesh
  • Lucy Brandriet BSc Biomedical Sciences and Synthetic Organic Chemistry (Natural Sciences) from University College London,

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Do you recognise this syndrome with a lengthy name? Do you struggle to grasp this medical condition? Chanarin-Dorfman Syndrome (CDS) is extremely rare, with a few reported cases worldwide. In the world of genetic disorders, it's like looking for a needle in a haystack.

A rare genetic disease called CDS is distinguished by dry, scaly skin at birth, developing fatty liver disease, and varying degrees of muscular involvement. The accumulation of lipid droplets in numerous cells all over the body is one of the distinguishing characteristics of CDS.

To give you a thorough grasp of this unusual disorder, we'll go into further detail on the genetic condition, clinical manifestations, diagnosis, and treatment of CDS. Keep reading to unlock the complete picture of CDS.


The Chanarin-Dorfman Syndrome (CDS) is a rare, multisystemic, autosomal recessive hereditary, neutral lipid storage disease (NLSD) due to recessive mutations in the abhydrolase domain containing the 5 (ABHD5) gene.  These mutations lead to the accumulation of lipid droplets in various cell types Importantly, this disease relates to a decrease in lipolysis activity in different tissue cells. Jordan first noticed leukocytes in the cytoplasm of leukocytes from the peripheral blood smear of two brothers with progressive muscular dystrophy in 1953. In the following two decades, Dorfman and Chanarin first described a neutral lipid storage disease marked by lipid buildup in peripheral blood white blood cells, bone marrow granulocyte precursors, liver cells, and numerous other cells in the body. There have been approximately 120 cases of CDS recorded worldwide. Assigned males at birth (AMAB) and assigned females at birth (AFAB) reported a similar rate of CDS, although AMAB experienced symptoms it at a higher rate. The youngest and oldest patients ranged from six months to 68 years. 

Around the world, roughly half of the people diagnosed with this syndrome have consanguineous parents, meaning sharing a common ancestor, typically through marriages between close relatives like first cousins. Particularly, countries and regions like Turkey, India, and the Middle East had consanguineous marriage rates higher than the global average. These locations had higher rates of homozygotic and heterozygotic patients than the other regions. The comparative gene identification-58 (CGI-58), situated on the 3p21 chromosome and known as the abhydrolase domain-containing 5 (ABHD5) gene, is relevant for the syndrome. Ichthyosis and intracytoplasmic lipid droplets are two of CDS patients' main clinical symptoms. Hepatocytes, intestinal mucosa, blood, bone marrow, skin fibroblasts, myocytes, central nervous system cells, and many other types of cells contain these lipid droplets. Different types of mutations contribute to the wide variation of clinical symptoms in CDS patients.1

Causes of the chanarin-dorfman syndrome

Mutations in the ABHD5 gene found on chromosome 3 result in CDS. 

CGI-58, a protein that plays a role in fat metabolism, is produced by this gene. Because it aids the major enzyme, adipose triacylglycerol lipase (ATGL), in its action, this protein is referred to as a cofactor. 

This enzyme's function is to degrade a specific kind of fat called triacylglycerol (TAG). Either an inefficient enzyme or a helper protein interrupts the process. Triacylglycerol, a type of fat, cannot be broken down and builds up as lipid droplets throughout the body, resulting in a broad spectrum of symptoms. This group of disorders are called "neutral lipid storage disease". It consists of two types:

Neutral lipid storage disorder with MyopathyWhen the major enzyme's gene (ATGL) is mutated.
Fat accumulation and the beginning of cardiac problems (cardiomyopathy) cause muscle abnormalities in early adulthood.
Neutral lipid storage disease with ichthyosis or Chanarin-Dorfman syndromeWhen the helper protein (CGI-58) gene is mutated.
Skin abnormalities present at birth with the absence of cardiomyopathy.

A person with CDS receives a defective gene from each parent since inheritance occurs through an autosomal recessive pattern. Even though they don't show any symptoms, individuals possessing one healthy gene and one disease-causing gene are carriers of the condition. With each pregnancy, there is a 25% chance that two carriers will both pass on the defective gene to their offspring and cause them to be affected. With each pregnancy, there is a 50% chance that the offspring is a carrier, like the parents. A child has a 25% chance of inheriting healthy genes from both parents.2

Signs and symptoms

Although the clinical manifestation of CDS might differ from person to person, some typical symptoms and signs entail,

  • Dark pigmentation, fine scaling, and intense itching cause skin picking and scratching. "Ichthyosiform nonbullous erythroderma" is the term used to describe the skin condition.
  • Skeletal and cardiac muscle myopathy
  • Liver damage
  • Ataxia
  • Neurosensory hearing loss
  • Cataract
  • Nystagmus
  • Strabismus
  • Growth and mental retardation
  • Short stature

There have also been occasional cases of


It can be challenging to diagnose CDS because it is a rare genetic condition with a variety of symptoms, and the testing process might vary based on how each person presents. These are the essential steps in CDS diagnosis: 

  • Clinical assessment

A thorough physical examination occurs to evaluate the patient's symptoms and spot any physical anomalies connected to CDS, including firm, non-tender hepatomegaly, muscle weakness, and neurological signs. These include generalised squamous skin lesions in the dorsal spine, abdomen, arms, and legs, including all flexures. A review of the patient's medical background, family history, and developmental milestones is crucial.

  • Laboratory tests

Lipid levels, liver function, and other metabolic markers are all evaluated by blood testing. Elevated levels of creatine phosphokinase (CPK), alkaline phosphatase (ALP), and alanine transaminase (ALT) are present in the serum. The patient's peripheral blood smear revealed lipid vacuoles in various immune cells, including neutrophils, eosinophils, and monocytes, consistent with Jordan's anomaly. A skin sample showed acanthosis, hyperkeratosis, and lipid vacuoles in the basal layer. During a needle biopsy, the liver's portal tracts exhibit fibrosis with an inflammatory infiltration and diffuse, severe fatty changes in the hepatocytes.

  • Imaging studies

Imaging techniques help to assess the size and condition of the liver and other internal organs. Abdominal ultrasonography assists in identifying moderate hepatomegaly with enhanced echotexture suggestive of fatty liver, splenomegaly, parenchymal calcifications in the spleen, and bilateral renal cortical cysts. Periurethral calcification of the prostate gland was visible on pelvic ultrasonography. Echocardiography identifies left ventricular hypertrophy (LVH) in some cases.

  • Genetic testing

The gold standard for diagnosing CDS is genetic testing. It entails sequencing the patient's DNA to find ABHD5 gene mutations associated with CDS.4,5

Management and treatment

The goal of managing and treating CDS is to reduce its symptoms and complications. A multidisciplinary approach and individualised care plans are used in CDS management because there is no known cure.

For the medical management of patients with this condition, emollients and retinoids are essential for the skin and muscle manifestations. Applying Skin moisturisers to soothe itching and other skin issues is preferred. Vitamin A derivatives like acitretin are therapeutic for skin and muscle symptoms but are frequently prohibited if the liver enzymes are compromised. Utilising acitretin has been reported to relieve skin discomfort without harming liver function. One liver transplant case followed by the customary dietary adjustments has been documented, with stabilisation of the skin and deterioration of intellectual disability after one year. There is insufficient research to conclude liver transplantation's efficacy and long-term effects.

Genetic counselling is essential for affected individuals and their families. Making informed judgements about family planning gets easier by explaining the genetic inheritance pattern of CDS. Regular medical follow-up and a cooperative healthcare team are necessary for providing comprehensive support throughout the individual's life. A rare illness like CDS can make daily life difficult. Two types of psychosocial care, counselling and support groups, can help individuals and families deal with the psychological and emotional impacts of the condition.2,3


What is the recommended diet for Chanarin-Dorfman syndrome?

When started early and combined with vitamin E (10 mg/kg/day) and ursodeoxycholic acid (15–20 mg/kg/day), a low-fat diet and medium-chain triglyceride supplements may reduce hepatomegaly and normalise hepatic enzyme levels. By the conclusion of the first year of the diet modification, the liver size of a patient with neutral lipid storage disease and ichthyosis who was on this diet had decreased by 50%, and following five years on this diet, skin lesions had significantly improved.6

Can prenatal testing detect CDS in an unborn child?

Foetal skin biopsy is feasible for prenatal diagnosis at 20 weeks. Prenatal detection occurs via the detection of specific lipid vacuoles in amniocytes or leukocytes (obtained through foetal blood sampling); nonetheless, this method is still under review for its potential therapeutic use.7

What is the life expectancy for individuals with CDS?

A retrospective study of 21 CDS patients revealed normal life expectancy but reduced quality of life due to severe pruritus, despair, and deafness.8


Given the rarity of CDS, medical professionals must collaborate closely with the patient and their family to develop an effective treatment plan after establishing a diagnosis through genetic testing and other clinical evaluations. Consult a healthcare practitioner for advice and assistance if you think you may have CDS or if it runs in your family. Remember that each person's experience with CDS is distinct, and customised treatment plans are required to meet the needs of each patient.


  1. Cakmak E, Bagci G. Chanarin‐dorfman syndrome: a comprehensive review. Liver International [Internet]. 2021 May [cited 2023 Sep 11];41(5):905–14. Available from: https://onlinelibrary.wiley.com/doi/10.1111/liv.14794
  2. Chanarin-dorfman syndrome - symptoms, causes, treatment | nord [Internet]. [cited 2023 Sep 11]. Available from: https://rarediseases.org/rare-diseases/ichthyosis-chanarin-dorfman-syndrome/
  3. Aksu AÜ, Sarı S, Gürkan ÖE, Dalgıç B. Chanarin–Dorfman syndrome: a novel mutation in a Turkish girl. [Internet]. [cited 2023 Sep 13] The Turkish Journal of Pediatrics 2015; 57: 300-303; 2014. Available from: https://www.turkishjournalpediatrics.org/uploads/pdf_TJP_1480.pdf
  4. Çuhaci F, Mutluay R, Aksakal B, Erten Y. A case with full clinical manifestations of Dorfman-Chanarin syndrome. Open Medicine [Internet]. 2007 Mar 1 [cited 2023 Sep 13];2(1):116–21. Available from: https://www.degruyter.com/document/doi/10.2478/s11536-007-0010-x/html
  5. Gandhi V, Aggarwal P, Dhawan J, Singh UR, Bhattacharya SN. Dorfman-Chanarin syndrome. IJDVL [Internet]. 2007 Jan 1 [cited 2023 Sep 13];73:36. Available from: https://ijdvl.com/dorfman-chanarin-syndrome/
  6. AlNeyadi R, Abdelhadi S, Ruszczak Z. Chanarin-Dorfman syndrome treatment with acitretin. JAAD Case Rep [Internet]. 2022 Mar 31 [cited 2023 Sep 13];24:11–3. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9062725/
  7. Tullu MS, Muranjan MN, Save SU, Deshmukh CT, Khubchandani SR, Bharucha BA. Dorfman-Chanarin Syndrome: A Rare Neutral Lipid Storage Disease [Internet]. Home | Indian Pediatrics. [cited 2023 Sep 14].Indian Pediatrics 2000;37: 88-93 Available from: https://www.indianpediatrics.net/jan2000/case2.htm
  8. Habash N, Wang Y, Morava E, Ibrahim SH. An adolescent with chanarin-dorfman syndrome presenting with ichthyosis and hepatic steatosis. JPGN Reports [Internet]. 2021 Nov [cited 2023 Sep 14];2(4):e137. Available from: https://journals.lww.com/jpgnr/Fulltext/2021/11000/An_Adolescent_with_Chanarin_Dorfman_Syndrome.20.aspx

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This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Deepika Rana

Bachelor of Dental Surgery(BDS), Dentistry , H.P.Government Dental College, IGMC Shimla.Himachal Pradesh

Hi, I am Deepika Rana Dentist by profession finished my Clinical Research Certification Programme from Duke NUS Medical school, Singapore in 2022. I joined Klarity’s internship because of my ongoing desire to learn and educate others about medicine through Writing. I enjoy producing articles that give readers detailed information about a variety of ailments that can be accessed through the Health Library created by Klarity.

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