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Disease Profile

Freeman-Sheldon syndrome

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

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Neonatal

ICD-10

Q87.0

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.

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)

FSS; Arthrogryposis distal type 2A; Whistling face-windmill vane hand syndrome;

Categories

Congenital and Genetic Diseases

Summary

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]

Symptoms

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]

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
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

Cause

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]

Diagnosis

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]

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 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

    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 Supporting this Disease

      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

        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.

          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.

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