Freeman-Sheldon syndrome

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Disease Profile

<1 / 1 000 000

US Estimated

Europe Estimated

Age of onset

Neonatal

ICD-10

Q87.0

Inheritance

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.

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

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.

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.

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

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.

Not applicable

Other names (AKA)

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

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 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: https://www.faces-cranio.org/ Freeman-Sheldon Research Group, Inc. Website: https://www.fsrgroup.org/ 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 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. References 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. 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. 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. 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. ARTHROGRYPOSIS, DISTAL, TYPE 2A; DA2A. Online Mendelian Inheritance in Man. Updated 6/13/2019; https://www.omim.org/entry/193700. Rare Endocrinology News Features Rare Disease Profiles 5 Facts Rare IQ Rare Mystery Spotlight On News Contact Us Advertising and Sponsorship About The Rare Medical Network Our mission is to inform the healthcare community about the diagnosis and management of rare diseases. Help us by sharing this important information with your peers. Rare Medical News websites sources information from: Orpha Net, The Genetic and Rare Diseases Information Center (GARD), PubMed and ClinicalTrials.gov. Rare Endocrinology News is strictly a news and information website about rare diseases. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. © 2023 Rare Endocrinology News. All Rights Reserved. Privacy Policy \| Terms of Service The Rare Medical Network Rare Cardiology News Rare Dermatology News Rare Endocrinology News Rare Gastroenterology News Rare Hematology News Rare Infectious Disease News Rare Immunology News Rare Nephrology/Urology News Rare Neurology News Rare Oncology News Rare Ophthalmology News Rare Pediatrics News Rare Primary Care News Rare Psychiatry News Rare Pulmonology News Rare Rheumatology News

Rare Endocrinology News

Rare Endocrinology News

Neonatal

Q87.0

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

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.

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.

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

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.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Cause

Diagnosis

Testing Resources

Treatment

Organizations

Organizations Supporting this Disease

Learn more

Where to Start

In-Depth Information

References

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.

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