Disease Profile

Larsen 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.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of Onset

Infancy

ageofonset-infancy.svg

ICD-10

Q74.8

Inheritance

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

rnn-autosomaldominant.svg

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

no.svg

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.

no.svg

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

no.svg

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.

no.svg

Not applicable

no.svg

Other Names (AKA)

LRS; Autosomal dominant Larsen syndrome

Categories

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

Summary

Larsen syndrome is a disorder of the development of the bones. Signs and symptoms may include clubfoot and numerous joint dislocations at birth (affecting the hips, knees and elbows); flexible joints; and a distinctive appearance of the face, hands, feet, and fingers, with square-shape finger tips. The X-rays usually show small extra bones in their wrists and ankles. Other features may include short stature, hypermobility, cleft palate, hearing loss, and an abnormal curvature of the spine that may result in weakness of the arms and/or legs and other complications. Larsen syndrome is inherited in an autosomal dominant manner and is caused by mutations in the FLNB gene.[1][2][3] Treatment depend on the problems that are present, and may include surgeries for hip dislocation, and/or to stabilize the spine, and/or to correct a cleft palate. Physiotherapy is indicated in most cases.[1][3]

There are several bone disorders that are caused by mutations in the FLNB gene. Some are considered mild (spondylocarpotarsal synostosis (SCT) syndrome and Larsen syndrome) and other are more severe (atelosteogenesis types I (AOI) and III (AOIII) and boomerang dysplasia).[3]

Symptoms

The signs and symptoms of Larsen syndrome vary from person to person, but may include the following:[4][2][3]

  • Joint dislocation (especially of the hips, knees, and elbows)
  • Hypermobile joints
  • Characteristic face such as flat, rectangular face, depressed nasal bridge, prominent forehead, and widely spaced eyes (hypertelorism)
  • Long fingers with broad ends (spatula-like) especially of the thumbs, and short nails
  • Short arms
  • Cleft palate
  • Clubfoot
  • Curved spine (scoliosis and kyphosis) that may compress the spinal cord and lead to weakness of the arms and/or legs, and other problems
  • Short stature
  • Breathing problems in infancy (due to soft cartilage in the airway)
  • Heart (cardiovascular) anomalies
  • Hearing loss
  • Small extra bones in the wrists and ankles that may be seen in the X-rays.

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
Brachydactyly
Short fingers or toes
0001156
Broad distal phalanx of finger
Broad outermost finger bone
0009836
Broad thumb
Broad thumbs
Wide/broad thumb

[ more ]

0011304
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Flat face
Flat facial shape
0012368
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Joint hyperflexibility
Joints move beyond expected range of motion
0005692
Large joint dislocations
0005008
Malar flattening
Zygomatic flattening
0000272
Prominent forehead
Pronounced forehead
Protruding forehead

[ more ]

0011220
Short distal phalanx of finger
Short outermost finger bone
0009882
Short nail
Short nails
0001799
30%-79% of people have these symptoms
Accessory carpal bones
0004232
5%-29% of people have these symptoms
Abnormality of epiphysis morphology
Abnormal shape of end part of bone
0005930
Abnormality of the cardiovascular system
Cardiovascular abnormality
0001626
Abnormality of the cervical spine
Abnormal cervical spine
0003319
Cleft palate
Cleft roof of mouth
0000175
Conductive hearing impairment
Conductive deafness
Conductive hearing loss

[ more ]

0000405
Craniosynostosis
0001363
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Finger syndactyly
0006101
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Laryngotracheomalacia
0008755
Respiratory insufficiency
Respiratory impairment
0002093
Scoliosis
0002650
Short stature
Decreased body height
Small stature

[ more ]

0004322
Vertebral segmentation defect
0003422
Percent of people who have these symptoms is not available through HPO
Aortic aneurysm
Bulge in wall of large artery that carries blood away from heart
0004942
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers

[ more ]

0001631
Autosomal dominant inheritance
0000006
Beaking of vertebral bodies
0004568
Bipartite calcaneus
0008127
Bronchomalacia
0002780
Cervical kyphosis
Rounded neck
0002947
Cleft upper lip
Harelip
0000204
Corneal opacity
0007957
Dislocated wrist
Dislocations of the wrists
0003994
Elbow dislocation
Dislocations of the elbows
Elbow dislocations

[ more ]

0003042
Frontal bossing
0002007
Hip dislocation
Dislocated hips
Dislocation of hip

[ more ]

0002827
Hypodontia
Failure of development of between one and six teeth
0000668
Hypoplastic cervical vertebrae
0008434
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Joint laxity
Joint instability
Lax joints
Loose-jointedness
Loosejointedness

[ more ]

0001388
Knee dislocation
0004976
Multiple carpal ossification centers
0006067
Pectus carinatum
Pigeon chest
0000768
Pectus excavatum
Funnel chest
0000767
Shallow orbits
Decreased depth of eye sockets
Shallow eye sockets

[ more ]

0000586
Short metacarpal
Shortened long bone of hand
0010049
Short metatarsal
Short long bone of foot
0010743
Spatulate thumbs
Spoon shaped thumbs
0001222
Spina bifida occulta
0003298
Spinal cord compression
Pressure on spinal cord
0002176
Spondylolysis
0003304
Talipes equinovalgus
0001772
Talipes equinovarus
Club feet
Club foot
Clubfeet
Clubfoot

[ more ]

0001762
Tracheal stenosis
Narrowing of windpipe

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

    • Genetics Home Reference (GHR) contains information on Larsen 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

      • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
      • 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 Larsen syndrome. Click on the link to view a sample search on this topic.

        References

        1. Autosomal dominant Larsen syndrome. Orphanet. July, 2013; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=503.
        2. Larsen syndrome. Genetics Home Reference. September, 2011; https://ghr.nlm.nih.gov/condition/larsen-syndrome.
        3. Robertson S. FLNB-Related Disorders. GeneReviews. October 17, 2013; https://www.ncbi.nlm.nih.gov/books/NBK2534/.
        4. Wiedemann HR, Kunze J, Grosse FR. In: Mosby-Wolfe. Clinical Syndromes. Italy: 1997; 3th: