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Freeman-Sheldon syndrome


Información en español Title


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Other Names:
FSS; Arthrogryposis distal type 2A; Whistling face-windmill vane hand syndrome; FSS; Arthrogryposis distal type 2A; Whistling face-windmill vane hand syndrome; Craniocarpotarsal dystrophy; Craniocarpotarsal dysplasia; DA2A; Distal arthrogryposis type 2A; Freeman-Burian syndrome See More
Categories:
Congenital and Genetic Diseases
This disease is grouped under:
Distal arthrogryposis; Myosinopathies

Summary Summary


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Freeman-Sheldon syndrome (FSS) affects the development of the bones, joints, head, and face. Symptoms of FSS are present from birth, and include abnormally flexed joints (joint contractures), spine abnormalities, and a characteristic facial appearance. People with FSS have a small mouth (microstomia) with pursed lips, giving the appearance of a "whistling face". In addition, they may have deep nasolabial folds (the skin between the nose and the lips) and a V-shaped chin dimple. There may be abnormalities of the eyes such as wide-spaced eyes (hypertelorism) and a narrowing of the eye opening (blepharophimosis). People with FSS often have breathing, eating, and speech problems. The joint and spine problems may get worse over time. FSS is thought to be caused by variants in the MYH3 gene. Most cases occur by chance. Rarely, FSS is inherited in an autosomal dominant manner. Diagnosis is based on a specific set of symptoms, clinical exam, and may be confirmed by the results of genetic testing. Treatment is focused on managing the symptoms and may involve corrective surgery.[1][2][3][4]
Last updated: 10/5/2020

Symptoms Symptoms


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The following list includes the most common signs and symptoms in people with Freeman-Sheldon syndrome. 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.

Symptoms may include:[1][4]
  • Small mouth with pursed lips ("whistling face")
  • Deep nasolabial folds (the skin between the nose and the lips)
  • V-shaped chin dimple
  • Abnormally flexed joints (joint contractures)
  • Narrow opening for the eye (blepharophimosis)
  • Club feet (talipes equinovarus)
  • Curvature of the spine
The symptoms of FSS are present at birth. As infants and children, people with FSS may have breathing, feeding, and speech problems. Joint and spine abnormalities may cause delays with motor skills, such as standing and walking. Joint and spine problems often get worse with age. People with FSS usually have average intelligence. Some people have psychosocial issues related to their appearance and joint limitations.[1]
Last updated: 10/5/2020

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.

Showing of 79 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of the dentition
Abnormal dentition
Abnormal teeth
Dental abnormality
[ more ]
0000164
Camptodactyly of finger
Permanent flexion of the finger
0100490
Depressed nasal ridge
Flat nose
Recessed nasal ridge
[ more ]
0000457
Dimple chin
Chin butt
Chin dent
Chin dimple
Chin skin dimple
Indentation of chin
[ more ]
0010751
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Failure to thrive
Faltering weight
Weight faltering
[ more ]
0001508
Feeding difficulties in infancy 0008872
Hypertelorism
Wide-set eyes
Widely spaced eyes
[ more ]
0000316
Joint stiffness
Stiff joint
Stiff joints
[ more ]
0001387
Narrow mouth
Small mouth
0000160
Scoliosis 0002650
Talipes equinovarus
Club feet
Club foot
Clubfeet
Clubfoot
[ more ]
0001762
Ulnar deviation of finger
Finger bends toward pinky
0009465
Underdeveloped nasal alae
Underdeveloped tissue around nostril
0000430
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge
[ more ]
0000431
30%-79% of people have these symptoms
Cryptorchidism
Undescended testis
Undescended testes
[ more ]
0000028
Deeply set eye
Deep set eye
Deep-set eyes
Sunken eye
[ more ]
0000490
Hearing impairment
Hearing defect
Deafness
[ more ]
0000365
Long philtrum 0000343
Malignant hyperthermia 0002047
Nasal speech
Nasal voice
0001611
Neurological speech impairment
Speech disorder
Speech impairment
Speech impediment
[ more ]
0002167
Prenatal movement abnormality 0001557
Ptosis
Drooping upper eyelid
0000508
Short stature
Decreased body height
Small stature
[ more ]
0004322
Strabismus
Cross-eyed
Squint eyes
Squint
[ more ]
0000486
5%-29% of people have these symptoms
Absent palmar crease
Absent palm lines
0010489
Hernia 0100790
Oligohydramnios
Low levels of amniotic fluid
0001562
Polyhydramnios
High levels of amniotic fluid
0001561
1%-4% of people have these symptoms
Arthralgia
Joint pain
0002829
Decreased fetal movement
Less than 10 fetal movements in 12 hours
0001558
Dental crowding
Crowded teeth
Dental overcrowding
Overcrowding of teeth
[ more ]
0000678
Elbow flexion contracture
Contractures of elbows
Elbow contracture
Elbow contractures
[ more ]
0002987
Flexion contracture of finger 0012785
Hip contracture 0003273
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ]
0001249
Joint dislocation
Joint dislocations
Recurrent joint dislocations
[ more ]
0001373
Knee flexion contracture 0006380
Motor delay 0001270
Recurrent fractures
Increased fracture rate
Increased fractures
Multiple fractures
Multiple spontaneous fractures
Varying degree of multiple fractures
[ more ]
0002757
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections
[ more ]
0002205
Restricted neck movement due to contractures
Restricted neck mobility due to contractures
0005997
Wrist flexion contracture 0001239
Percent of people who have these symptoms is not available through HPO
Abnormal auditory evoked potentials 0006958
Abnormality of the skin 0000951
Adducted thumb
Inward turned thumb
0001181
Autosomal dominant inheritance 0000006
Blepharophimosis
Narrow opening between the eyelids
0000581
Breech presentation
Feet or buttocks of fetus positioned near opening of uterus
0001623
Camptodactyly
Permanent flexion of the finger or toe
0012385
Cerebellar atrophy
Degeneration of cerebellum
0001272
Chin with H-shaped crease
Chin, H-Shaped Crease
Chin, H-shaped groove
H-shaped dimple of the chin
[ more ]
0011824
Epicanthus
Eye folds
Prominent eye folds
[ more ]
0000286
Flat face
Flat facial shape
0012368
Flexion contracture of toe 0005830
High palate
Elevated palate
Increased palatal height
[ more ]
0000218
Hip dislocation
Dislocated hips
Dislocation of hip
[ more ]
0002827
Hypoplasia of the brainstem
Small brainstem
Underdeveloped brainstem
[ more ]
0002365
Inguinal hernia 0000023
Joint contracture of the hand 0009473
Kyphoscoliosis 0002751
Malar flattening
Zygomatic flattening
0000272
Mandibular prognathia
Big lower jaw
Increased projection of lower jaw
Increased size of lower jaw
Large lower jaw
Prominent chin
Prominent lower jaw
[ more ]
0000303
Mask-like facies
Expressionless face
Lack of facial expression
Mask-like facial appearance
[ more ]
0000298
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ]
0000252
Muscle weakness
Muscular weakness
0001324
Postnatal growth retardation
Growth delay as children
0008897
Prominent forehead
Pronounced forehead
Protruding forehead
[ more ]
0011220
Rocker bottom foot
Rocker bottom feet
Rocker-bottom feet
Rockerbottom feet
[ more ]
0001838
Seizure 0001250
Short neck
Decreased length of neck
0000470
Short nose
Decreased length of nose
Shortened nose
[ more ]
0003196
Shoulder flexion contracture 0003044
Small for gestational age
Birth weight less than 10th percentile
Low birth weight
[ more ]
0001518
Spina bifida occulta 0003298
Telecanthus
Corners of eye widely separated
0000506
Ulnar deviation of the hand or of fingers of the hand 0001193
Whistling appearance
Whistling facial appearance
0000346
Showing of 79 |
Do you have more information about symptoms of this disease? We want to hear from you.
Last updated: 2/1/2021

Cause Cause


Listen
In most cases, Freeman-Sheldon syndrome (FSS) is caused by the MYH3 gene not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all. In some individuals with FSS, no MYH3 gene variant has been found. The cause of FSS in these individuals is unknown.[1][4][5] 
Last updated: 10/5/2020

Inheritance Inheritance


Listen
Occasionally, Freeman-Sheldon syndrome (FSS) is inherited in an autosomal dominant pattern.[5] All individuals inherit two copies of each gene. Autosomal means the gene is found on one of the numbered chromosomes found in both sexes. Dominant means that only one altered copy of a gene is necessary to have the condition. The alteration can be inherited from either parent.  Sometimes an autosomal dominant condition occurs because of a new genetic alteration (de novo) and there is no history of this condition in the family. This is generally true for Freeman-Sheldon syndrome, as most cases occur by chance.
  
Each child of an individual with an autosomal dominant condition has a 50% or 1 in 2 chance of inheriting the alteration and the condition. Typically, children who inherit a dominant alteration will have the condition, but they may be more or less severely affected than their parent.  Sometimes a person may have a gene alteration for an autosomal dominant condition and show no signs or symptoms of the condition.
Last updated: 10/5/2020

Diagnosis Diagnosis


Listen
Freeman Sheldon syndrome (FSS) is diagnosed based on the symptoms and clinical exam. Symptoms important for diagnosis include the characteristic facial features (small mouth, deep nasolabial folds, V-shaped chin dimple) and the presence of joint abnormalities. Imaging studies, such as CT scan and X-ray be be helpful to determine the presence and severity of features. The results of genetic testing may be helpful to confirm the diagnosis.[1][4]
Last updated: 10/5/2020

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment Treatment


Listen
Treatment for Freeman-Sheldon syndrome (FSS) is focused on managing the symptoms. Surgery may help correct or improve the facial, joint, and spine abnormalities. Physical and occupational therapy may be helpful for strengthening joints. Some people with FSS benefit from talking to a mental health specialist.[1][3][4]

Specialists involved in the care of someone with FSS may include:
  • Craniofacial surgeon
  • Orthopedist
  • Ophthalmologist
  • Otolaryngologist
  • Speech language pathologist
  • Physical therapist
  • Psychologist
Last updated: 10/5/2020

Statistics Statistics


Listen
It is unknown exactly how many people have Freeman-Sheldon syndrome. It has been estimated that about one in 1,000,000 people has this condition, but this has not been confirmed.[1]
Last updated: 10/5/2020
Do you have updated information on this disease? We want to hear from you.

Find a Specialist Find a Specialist


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If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

  • To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from MedlinePlus Genetics.

Research Research


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Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Freeman-Sheldon syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Organizations Organizations


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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 Supporting this Disease

  • Arthrogryposis Multiplex Congenita Support Inc.
    P.O. Box 6291
    Spartanburg, SC 29304
    Toll-free: 1-805-55-AMCSI (1-805-552-6274)
    Telephone: +1-805-552-6274
    E-mail: bod@amcsupport.org
    Website: https://amcsupport.org
  • FACES: The National Craniofacial Association
    PO Box 11082
    Chattanooga, TN 37401
    Toll-free: 800-332-2373
    Telephone: 423-266-1632
    E-mail: faces@faces-cranio.org
    Website: http://www.faces-cranio.org/
  • Freeman-Sheldon Research Group, Inc.
    Website: http://www.fsrgroup.org/
Do you know of an organization? We want to hear from you.

Learn More Learn More


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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

  • FACES: The National Craniofacial Association offers an information page on Freeman-Sheldon syndrome. Please click on the link to access this resource.
  • MedlinePlus Genetics contains information on Freeman-Sheldon syndrome. This website is maintained by the National Library of Medicine.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

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 Freeman-Sheldon syndrome. Click on the link to view a sample search on this topic.

News & Events News & Events


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News

  • Rare Disease Day at NIH 2021
    March 1, 2021

GARD Answers GARD Answers


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Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

Have a question? Contact a GARD Information Specialist.

References References


  1. Poling MI, Dufresne CR, Chamberlain RL. Freeman-Burian syndrome. Orphanet J Rare Dis. Jan 10, 2019; 14(1):14. https://pubmed.ncbi.nlm.nih.gov/30630514.
  2. Chamberlain RL, Poling MI, Portillo AL, Morales A, Ramirez RR, McCormick RJ. Freeman-Sheldon syndrome in a 29-year-old woman presenting with rare and previously undescribed features. BMJ Case Rep. Oct 22, 2015; 2015:bcr2015212607. https://pubmed.ncbi.nlm.nih.gov/26494722.
  3. Poling MI, Dufresne CR, Portillo AL. Identification and Recent Approaches for Evaluation, Operative Counseling, and Management in Patients With Freeman-Burian Syndrome: Principles for Global Treatment. J Craniofac Surg.. Nov-Dec, 2019;; 30(8):2502-2508. https://pubmed.ncbi.nlm.nih.gov/31567769.
  4. Poling MI, Dufresne CR, Chamberlain RL. Findings, Phenotypes, Diagnostic Accuracy, and Treatment in Freeman-Burian Syndrome. J Craniofac Surg. Jun, 2020; 31(4):1063-1069. https://pubmed.ncbi.nlm.nih.gov/32149971.
  5. ARTHROGRYPOSIS, DISTAL, TYPE 2A; DA2A. Online Mendelian Inheritance in Man. Updated 6/13/2019; https://www.omim.org/entry/193700.
Do you know of a review article? We want to hear from you.
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