King Denborough syndrome

King-Denborough Syndrome: A Rare Genetic Disorder

King-Denborough syndrome (KDS) is a rare congenital myopathy characterized by the triad of congenital myopathy, dysmorphic features, and susceptibility to malignant hyperthermia [4][8]. This autosomal dominant disorder affects individuals with a wide range of phenotypic expressions, including delayed motor development, muscle weakness and fatigability, ptosis, and facies myopathica (with or without creatine kinase elevations) [10].

The syndrome is often associated with skeletal abnormalities and dysmorphic craniofacial features, which are key diagnostic indicators [6][9]. Additionally, individuals with KDS may exhibit a range of physical characteristics, including short stature, delayed motor development, and muscle weakness [11].

It's essential to note that King-Denborough syndrome is a rare condition, and its diagnosis can be challenging. A definitive diagnosis requires a comprehensive evaluation, including a positive family history of malignant hyperthermia, the presence of muscle wasting, and/or an elevated CK level [5].

King Denborough Syndrome Signs and Symptoms

King Denborough syndrome, also known as King-Denborough syndrome (KDS), is a rare genetic disorder characterized by the triad of congenital myopathy, dysmorphic features, and susceptibility to malignant hyperthermia. The clinical features of KDS include:

• Abnormality of head or neck: Broad nasal tip, deep philtrum, downslanted palpebral fissures, high palate, low hanging columella, midface hypoplasia [1]
• Unusual facies: Often described as "Noonan-oid" with low-set ears, hypertelorism, downslanting palpebral fissures, ptosis, strabismus [3][5]
• Skeletal abnormalities: Variable dysmorphic features include malar hypoplasia, high-arched palate, dental crowding/malocclusion, micrognathia [6][9]

Additionally, individuals with KDS may also experience:

• Short stature [7]
• Congenital myopathy: A rare genetic non-dystrophic myopathy characterized by muscle weakness and wasting [4]
• Susceptibility to malignant hyperthermia: A life-threatening medical condition triggered by certain anesthetics and muscle relaxants [1][8]

These signs and symptoms can vary in severity and presentation, making KDS a complex and challenging condition to diagnose and manage.

References: [1] Context result 1 [2] Context result 2 [3] Context result 3 [4] Context result 4 [5] Context result 5 [6] Context result 6 [7] Context result 7 [8] Context result 8 [9] Context result 9

Diagnostic Tests for King-Denborough Syndrome

King-Denborough syndrome, a rare genetic non-dystrophic myopathy, requires specific diagnostic tests to confirm its presence. Here are the key diagnostic tests associated with this condition:

• Muscle Biopsy: A muscle biopsy is essential for diagnosing King-Denborough syndrome. The test involves taking a sample of muscle tissue from the affected individual and examining it under a microscope. This can help identify any abnormalities in the muscle fibers.
• Halothane-Caffeine Contracture Testing: This test is used to determine if an individual has malignant hyperthermia susceptibility, which is associated with King-Denborough syndrome. The test involves administering halothane and caffeine to the individual and measuring their muscle contractions.
• Creatine Phosphokinase (CPK) Levels: Elevated CPK levels can indicate muscle damage or disease, including King-Denborough syndrome. A mild elevation of CPK levels has been reported in some cases.
• Spinal X-rays: Spinal x-rays may be used to assess any spinal abnormalities, such as scoliosis and lordosis, which are associated with King-Denborough syndrome.

Clinical Trials and Genetic Tests

While not directly diagnostic tests for King-Denborough syndrome, clinical trials and genetic tests can provide valuable information about the condition. Clinical trials can help determine if a new test or treatment is effective and safe in treating King-Denborough syndrome. Genetic tests related to King-Denborough syndrome are also available, although these should only be used under medical supervision.

References

• [2] King-Denborough syndrome is a rare genetic non-dystrophic myopathy characterized by the triad of congenital myopathy, dysmorphic features and susceptibility to malignant hyperthermia.
• [5] Definitive diagnosis of associated MH susceptibility requires a muscle biopsy for halothane-caffeine contracture testing.
• [7] A muscle biopsy after a positive halothane-caffeine contracture test is required for definitive diagnosis.
• [9] Laboratory testing showed a mild elevation of creatine phosphokinase (CPK), and spinal x-rays demonstrated thoracolumbar scoliosis and lordosis.

Treatment Overview

King-Denborough syndrome (KDS) is a rare genetic disorder characterized by congenital myopathy, dysmorphic features, and susceptibility to malignant hyperthermia (MH). While there is no specific treatment for KDS, the main focus is on managing anesthesia-related complications such as MH.

• Dantrolene Administration: The primary treatment for malignant hyperthermia is a drug called dantrolene (Dantrium®) [5]. Anesthesiologists administer this medication immediately if they suspect MH in patients with KDS.
• Awareness of Anesthesia-Related Complications: Perioperative management in patients with KDS emphasizes awareness of anesthesia-related complications such as MH and potential airway problems [6].
• Muscle Biopsy for Diagnosis: Definitive diagnosis of associated MHS requires a muscle biopsy for halothane-caffeine contracture testing [7].

Existing Treatment

The existing treatment for King-Denborough syndrome involves the administration of Dantrolene intravenously and suspending exposure to triggering agents [8]. This approach is crucial in preventing MH episodes.

• Intravenous Dantrolene: Administering Dantrolene intravenously is a critical step in managing KDS patients, especially during anesthesia procedures.
• Avoidance of Triggering Agents: Sustaining exposure to triggering agents can lead to MH episodes. Therefore, it is essential to avoid these substances in patients with KDS.

References

[5] The main treatment for malignant hyperthermia is a drug called dantrolene (Dantrium®). [6] by O Nurumbetova — The main focus on perioperative management in patients with KDS is awareness of anesthesia-related complications such as MHS and potential airway problems. [7] Definitive diagnosis of associated MHS requires a muscle biopsy for halothane-caffeine contracture testing. [8] Jul 9, 2014 — King-Denborough syndrome Treatment​​ Existing treatment involves administration of Dantrolene intravenously; suspend exposure to triggering ...

Based on the provided context, it appears that King-Denborough syndrome has several differential diagnoses, which are conditions that can present with similar symptoms and need to be ruled out before a definitive diagnosis can be made.

According to search result [11], important differential diagnoses for King-Denborough syndrome include:

• Congenital Muscular Myopathy (CMS)
• Spinal Muscular Atrophy type 0 (SMA type 0)

Additionally, search result [9] mentions that the King-Denborough syndrome is a peculiar manifestation of certain RYR1 mutations associated with dysmorphic features and often multiple orthopaedic abnormalities.

It's worth noting that a definitive diagnosis of King-Denborough syndrome requires a muscle biopsy for halothane-caffeine contracture testing, as mentioned in search result [10].

Therefore, the differential diagnoses for King-Denborough syndrome include:

• Congenital Muscular Myopathy (CMS)
• Spinal Muscular Atrophy type 0 (SMA type 0)
• Other conditions associated with RYR1 mutations and dysmorphic features.

References: [9], [10], [11]