Rare Endocrinology News

Disease Profile

STAC3 Disorder

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

<1 / 1 000 000

US Estimated

Europe Estimated

Age of onset

Infancy

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ICD-10

G71.2

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Congenital myopathy cleft palate and malignant hyperthermia; Congenital myopathy cleft palate malignant hyperthermia; Congenital myopathy-cleft palate-malignant hyperthermia syndrome;

Categories

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Mouth Diseases;

Summary

STAC3 Disorder is a genetic condition that affects the muscles and skeleton. The main features are muscle weakness present at birth, club foot, fixed joints (joint contractures), and curvature of the spine. The symptoms of this condition vary. The most severe complications can include feeding and breathing difficulties. Many people with this condition are at risk to have complications under general anesthesia (malignant hyperthermia). Muscle weakness may get slowly worse over time or stay the same. Most people with STAC3 disorders are shorter than average and have normal intelligence. This condition is caused by genetic alterations in the STAC3 gene and is inherited in an autosomal recessive pattern. STAC3 disorder is diagnosed based on the symptoms and confirmed by genetic testing. Treatment is based on managing the symptoms.[1][2][3][4]

Symptoms

The following list includes the most common signs and symptoms in people with STAC3 disorder. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

  • Muscle weakness present at birth (congenital myopathy)
  • Low muscle tone (hypotonia)
  • Facial weakness
  • Down turned corners of the mouth
  • Drooping eyelids (ptosis)
  • Clubfoot (talipes)
  • Fixed joints (joint contractures)
  • Cleft palate
  • Increased risk for complications from general anesthesia (malignant hyperthermia)
  • Curvature of the spine (scoliosis)

STAC3 disorder is very rare and how the symptoms change over time has not been well described. The muscle weakness and curvature of the spine tend to slowly get worse, although some people with STAC3 disorder have mild symptoms that don't change. Most adults with STAC3 disorder are shorter than average and may have delayed motor skills (like walking and running). Intelligence is usually normal. A few have severe symptoms that result in very serious respiratory and feeding difficulties.[1][2]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Muscle weakness
Muscular weakness
0001324
Myopathic facies
0002058
30%-79% of people have these symptoms
Abnormality of skeletal muscle fiber size
0012084
Arthrogryposis multiplex congenita
0002804
Bilateral ptosis
Drooping of both upper eyelids
0001488
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

 0000028
Feeding difficulties
Feeding problems
Poor feeding

[ more ]

 0011968
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn

[ more ]

 0002020
Malignant hyperthermia
0002047
Motor delay
0001270
Muscular hypotonia
Low or weak muscle tone
0001252
Progressive congenital scoliosis
0008458
Respiratory insufficiency
Respiratory impairment
0002093
Short stature
Decreased body height
Small stature

[ more ]

 0004322
Skeletal muscle atrophy
Muscle degeneration
Muscle wasting

[ more ]

 0003202
Talipes equinovarus
Club feet
Club foot
Clubfeet
Clubfoot

[ more ]

 0001762
5%-29% of people have these symptoms
Bifid uvula
0000193
Conductive hearing impairment
Conductive deafness
Conductive hearing loss

[ more ]

 0000405
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Downturned corners of mouth
Downturned corners of the mouth
Downturned mouth

[ more ]

 0002714
Dysarthria
Difficulty articulating speech
0001260
High palate
Elevated palate
Increased palatal height

[ more ]

 0000218
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

 0001249
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

 0000347
Muscle fiber atrophy
Muscle fiber degeneration
0100295
Reduced tendon reflexes
0001315
Submucous cleft soft palate
0011819
Ventriculomegaly
0002119
1%-4% of people have these symptoms
Camptodactyly
Permanent flexion of the finger or toe
0012385
Facial hemangioma
0000329
Inability to walk
0002540
Intellectual disability, mild
Mental retardation, borderline-mild
Mild and nonprogressive mental retardation
Mild mental retardation

[ more ]

 0001256
Joint laxity
Joint instability
Lax joints
Loose-jointedness
Loosejointedness

[ more ]

 0001388
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Blepharophimosis
Narrow opening between the eyelids
0000581
Brachycephaly
Short and broad skull
0000248
Cleft palate
Cleft roof of mouth
0000175
Flexion contracture
Flexed joint that cannot be straightened
0001371
Hyporeflexia
Decreased reflex response
Decreased reflexes

[ more ]

 0001265
Kyphoscoliosis
0002751
Low-set ears
Low set ears
Lowset ears

[ more ]

 0000369
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

 0000252
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface

[ more ]

 0011800
Multiple skeletal anomalies
0005775
Ptosis
Drooping upper eyelid
0000508
Restrictive ventilatory defect
Stiff lung or chest wall causing decreased lung volume
0002091
Short palpebral fissure
Short opening between the eyelids
0012745
Talipes
0001883
Telecanthus
Corners of eye widely separated
0000506

Cause

STAC3 disorder is caused by genetic alterations (mutations) in the STAC3 gene.[1][2]

Diagnosis

STAC3 disorder is diagnosed based on the symptoms and is confirmed by genetic testing for alterations in the STAC3 gene. In some cases, other more common conditions are excluded before testing is done for STAC3 disorder.[1][2][3]

Testing Resources

  • Orphanet lists international laboratories offering diagnostic testing for this condition.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Providing General Support

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • The Muscular Dystrophy Association has developed a resource called "Facts About Myopathies" that discusses commonly asked questions regarding myopathies. Click on the link above to view this information page.

        In-Depth Information

        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss STAC3 Disorder. Click on the link to view a sample search on this topic.

          References

          1. Webb BD, Manoli I, Jabs EW. STAC3 Disorder. GeneReviews. Jun 20, 2019; https://www.ncbi.nlm.nih.gov/books/NBK542808.
          2. Zaharieva IT, Sarkozy A, Munot P, Manzur A, O’Grady G, Rendu J et al. STAC3 variants cause a congenital myopathy with distinctive dysmorphic features and malignant hyperthermia susceptibility. Human Mutaion. Dec 218; 39(12):1980-1994. https://pubmed.ncbi.nlm.nih.gov/30168660.
          3. Telegraphi A, Webb BD, Robbins SM, Speck-Martins CE, FitzPatrick D, et al. Identification of STAC3 variants in non-Native American families with overlapping features of Carey-Fineman-Ziter syndrome and Moebius syndrome. Am J Med Genet A. Oct 2017; 173(10):2763-2771. https://pubmed.ncbi.nlm.nih.gov/28777491.
          4. Grzybowski M, Schanzer A, Pepler A, Heller C, Neubauer BA, Hahn A. Novel STAC3 Mutations in the First Non-Amerindian Patient with Native American Myopathy. Neuropediatrics. Dec 2017; 48(6):451-455. https://pubmed.ncbi.nlm.nih.gov/28411587.
          5. Stamm DS, Aylesworth AS, Stajich JM, Kahler SG, Thorne LB, Speer MC, Powell CM. Native American myopathy: congenital myopathy with cleft palate, skeletal anomalies, and susceptibility to malignant hyperthermia. Am J Med Genet A. Jul 15, 2008; 146A(14):1832-41. https://ncbi.nlm.nih.gov/pubmed/18553514.

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