King-Denborough Syndrome: Causes, Symptoms and Care

Author: Thomas C. Weiss
Published: 9 Jul 2014 - Updated: 8 Nov 2026
Publication Type: Informative

Table of Contents:
Synopsis - Definition - Overview - FAQs - Insights, Updates - Related Content

Synopsis

This information explains King-Denborough syndrome, a rare inherited congenital myopathy defined by muscle weakness from early childhood, distinctive facial and skeletal features, and a high risk of malignant hyperthermia, a life-threatening reaction to some anesthetic drugs. It describes the genetics, including RYR1 and the more recently linked STAC3 gene, using a 2025 study in the European Journal of Human Genetics and MedlinePlus Genetics, and sets out the signs and symptoms, how the condition is diagnosed and distinguished from Noonan syndrome, and how malignant hyperthermia is prevented and treated. The page is useful for families, people living with congenital myopathies, and the surgeons, dentists and anesthesiologists who need to plan safe care.*

At a Glance

• 1 - Intelligence is usually normal in people with KDS.
• 2 - KDS was first described in 1973 by two Australian doctors, King and Denborough.
• 3 - A malignant hyperthermia crisis during surgery is sometimes the first sign of the condition.
• 4 - Relatives may carry the same gene change and should consider genetic counseling and testing before any surgery.

Topic Definition

King-Denborough Syndrome

King-Denborough syndrome is a rare inherited congenital myopathy characterized by muscle weakness from early life, distinctive physical features such as drooping eyelids, a small jaw, low-set ears, short stature and spinal curvature, and susceptibility to malignant hyperthermia during anesthesia. It is most often caused by variants in the RYR1 or STAC3 genes, which affect calcium release in muscle cells.

Overview

King-Denborough syndrome (KDS) is a rare inherited muscle disorder defined by three features: a congenital myopathy (muscle weakness present from birth or early childhood), distinctive facial and skeletal features, and susceptibility to malignant hyperthermia, a dangerous reaction to certain anesthetic drugs. It was first described in 1973 by the Australian doctors J. O. King and M. A. Denborough in children who had severe reactions during anesthesia. Many cases have since been linked to changes in the RYR1 gene, and more recently the STAC3 gene, which help control how muscle cells release calcium.

What Is King-Denborough Syndrome?

KDS is one of the congenital myopathies, a group of conditions in which muscles are weak from early life because of problems inside the muscle cells. What sets KDS apart is the combination of mild to moderate muscle weakness, a recognizable pattern of physical features that can resemble Noonan syndrome, and a high risk of malignant hyperthermia. Intelligence is usually normal. It is very rare, and its true frequency is not known.

Causes and Genetics

The RYR1 gene makes the ryanodine receptor, a channel that releases calcium inside muscle cells to trigger contraction. RYR1 variants are the most common known cause of malignant hyperthermia susceptibility and of several congenital myopathies, including central core disease, and they have been found in many people with KDS. In a 2025 study of 67 Black African patients with congenital myopathy, 44 were diagnosed with KDS, and the main causes were variants in both copies of either RYR1 or STAC3, inherited in an autosomal recessive pattern [Schoonen et al., 2025]. STAC3 variants also cause STAC3 disorder, sometimes called Native American myopathy, which shares weakness, facial features and malignant hyperthermia risk with KDS [MedlinePlus Genetics, n.d.-b]. Depending on the gene and variant, KDS can be inherited in a dominant or recessive way, and some cases have no identified genetic cause.

Signs and Symptoms of KDS

Features vary from person to person and may include:

• Muscle weakness, often mild and slowly progressive or stable, with delayed motor milestones in childhood
• Drooping upper eyelids (ptosis) and downward-slanting eyes
• Low-set ears, a small lower jaw (micrognathia) and underdeveloped cheekbones
• Short stature
• Curvature of the spine, such as scoliosis or kyphoscoliosis, and a prominent breastbone (pectus carinatum)
• Joint contractures
• Undescended testes (cryptorchidism) in boys
• Susceptibility to malignant hyperthermia

Malignant Hyperthermia: The Main Danger

Malignant hyperthermia is a life-threatening reaction to certain drugs used during surgery: volatile anesthetic gases and the muscle relaxant succinylcholine. In susceptible people these drugs cause uncontrolled calcium release in muscle, leading to a rapid rise in body temperature, muscle rigidity, a fast heart rate, high carbon dioxide levels and muscle breakdown [MedlinePlus Genetics, n.d.-a]. Without prompt treatment it can cause organ failure and death. It is treated by stopping the triggering drugs at once, giving the drug dantrolene, and cooling and supporting the patient. Because a reaction may be the first sign that a child has KDS, the condition is sometimes diagnosed only after a crisis during surgery.

Diagnosing KDS

Diagnosis is based on the combination of muscle weakness, typical physical features and a personal or family history of malignant hyperthermia. Tests may include blood levels of creatine kinase, a muscle enzyme that can be raised, genetic testing for RYR1, STAC3 and other myopathy genes, and sometimes a muscle biopsy. Specialized centers can test muscle tissue for malignant hyperthermia susceptibility with a contracture test. Doctors also need to distinguish KDS from Noonan syndrome, which shares some facial features but more often involves heart defects and does not cause a congenital myopathy.

Management and Living with KDS

There is no cure for KDS, but people can live full lives with good planning. Care usually involves a team that may include neurologists, geneticists, anesthesiologists, orthopedic specialists and physical therapists.

• Tell every surgeon, dentist and anesthesiologist about the diagnosis, and wear a medical alert ID, so that trigger-free anesthesia can be planned.
• Relatives may also carry the gene change and should ask about genetic counseling and testing before any surgery.
• Physical therapy can help maintain strength, mobility and joint range.
• Scoliosis, contractures and other orthopedic problems may need bracing or surgery, planned with the anesthesia team.
• The outlook depends mainly on the degree of muscle weakness and on avoiding malignant hyperthermia.

More on this topic: Health Publications - Bones and Joints Publications

Frequently Asked Questions

NOTE: Researched FAQs by Disabled World (DW)

Is King-Denborough syndrome the same as malignant hyperthermia?

No. Malignant hyperthermia is a drug reaction that can occur in people with KDS and in many people without it. KDS also includes muscle weakness and distinctive physical features.

Which anesthetics are safe for someone with KDS?

Anesthesiologists usually use trigger-free techniques that avoid volatile anesthetic gases and succinylcholine. The exact plan should always be made by the anesthesia team.

Can local anesthesia be used in people with malignant hyperthermia risk?

Local anesthetics used by dentists and for minor procedures are generally considered safe, but the dentist or doctor should always be told about the diagnosis.

What is dantrolene?

Dantrolene is a muscle relaxant that stops the abnormal calcium release in muscle during a malignant hyperthermia reaction. Hospitals that use triggering anesthetics keep it on hand.

Is there a test for malignant hyperthermia susceptibility?

Genetic testing can find known gene changes, and specialized centers offer a muscle contracture test using a small muscle sample.

Can people with KDS exercise?

Many can, and physical therapy is often recommended. Exercise plans should be discussed with a doctor, especially in hot conditions.

Is KDS life threatening?

The main danger is a malignant hyperthermia reaction, which can be fatal without treatment but can usually be prevented with proper anesthesia planning.

Where can families find support for congenital myopathies?

Neuromuscular disease organizations and malignant hyperthermia associations offer information, emergency guidance and connections with other families.

References

• MedlinePlus Genetics. (n.d.-a). Malignant hyperthermia. U.S. National Library of Medicine.
• MedlinePlus Genetics. (n.d.-b). STAC3 disorder. U.S. National Library of Medicine.
• Schoonen, M., Fassad, M., Patel, K., Bisschoff, M., Vorster, A., Makwikwi, T., et al. (2025). Biallelic variants in RYR1 and STAC3 are predominant causes of King-Denborough syndrome in an African cohort. European Journal of Human Genetics, 33, 421 - 431.

Insights, Analysis, and Developments

Editorial Note: King-Denborough syndrome is rare, but it carries a risk that is almost entirely preventable: a malignant hyperthermia reaction during surgery. That makes awareness the most powerful tool families have. A confirmed diagnosis, a medical alert ID and a clear message to every surgeon, dentist and anesthesiologist allow trigger-free anesthesia to be planned, and testing relatives can protect people who do not yet know they are at risk. Recent genetic research, including work in African populations who have been underrepresented in earlier studies, is widening the list of known causes and should make diagnosis faster and more accurate in the years ahead.*

Author Credentials: Thomas C. Weiss is a researcher and editor for Disabled World. Thomas attended college and university courses earning a Masters, Bachelors and two Associate degrees, as well as pursuing Disability Studies. As a CNA Thomas has provided care for people with all forms of disabilities. Explore Thomas' complete biography for comprehensive insights into his background, expertise, and accomplishments.

* Editorial additions by Ian C. Langtree.