Disease Profile

Fuhrmann 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

Infancy

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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

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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)

Bowing of the femurs, aplasia or hypoplasia of the fibula, and digital anomalies; Fibular aplasia or hypoplasia, femoral bowing and poly-, syn-, and oligodactyly

Categories

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

Summary

Fuhrmann syndrome is a very rare genetic syndrome characterized by skeletal abnormalities. It is a type of skeletal dysplasia. Signs and symptoms of Fuhrmann syndrome are present from birth and may include bowing of the femurs (the upper bones of the legs), having no fibula (lower bone of the leg) or a smaller fibula than usual, and having more fingers or toes than normal (polydactyly) or fewer fingers or toes than normal (oligodactyly).[1][2]

Fuhrmann syndrome is caused by mutations (changes) to the WNT7A gene and is inherited in an autosomal recessive manner.[1] Diagnosis of the syndrome can be made when a doctor observes signs and symptoms consistent with the syndrome.[3] The diagnosis can be confirmed by genetic testing. Treatment for Fuhrmann syndrome depends on the specific symptoms of each affected person, but may include surgical options.[4]

Symptoms

Signs and symptoms of Fuhrmann syndrome are present from birth and may include bowing of the femurs (the upper bones of the legs), having no fibula (lower bone of the leg) or a smaller fibula than usual, and having more fingers or toes than normal (polydactyly) or fewer fingers or toes than normal (oligodactyly). Some people with Fuhrmann syndrome may have fingers or toes that are fused together (syndactyly).[1][2] Less commonly, these skeletal differences may be seen in the arms as well as the legs.[1] Other signs and symptoms associated with Fuhrmann syndrome include an underdeveloped (hypoplastic) pelvisdislocation of the hips from birth, joints that are unable to bend properly (joint contractures) and hypoplastic fingers or fingernails. Some people with Fuhrmann syndrome have been born with cleft lip and/or palate.[1]

In some cases, doctors have found differences in the brains of people who have Fuhrmann syndrome when they look at them upon imaging. The brain differences can include a cerebellum that is not in the usual location and having smaller than typical folds in the brain (microgyria).[1] 

The signs and symptoms associated with Fuhrmann syndrome can be different from person to person within members of the same family and between different families affected by the syndrome.[5]

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
Aplasia/Hypoplasia of the fibula
Absent/small calf bone
Absent/underdeveloped calf bone

[ more ]

0006492
Aplasia/Hypoplasia of the ulna
Absence/underdevelopment of inner forearm bone
0006495
Femoral bowing
Bowed thighbone
0002980
Hypoplasia of the radius
Underdeveloped outer large forearm bone
0002984
Radial bowing
Bowing of outer large bone of the forearm
0002986
30%-79% of people have these symptoms
Abnormal finger flexion creases
0006143
Aplasia/Hypoplasia involving the metacarpal bones
Absent/small long bones of hand
Absent/underdeveloped long bones of hand

[ more ]

0005914
Aplasia/Hypoplasia of metatarsal bones
Absent/small long bone of foot
Absent/underdeveloped long bone of foot

[ more ]

0001964
Aplasia/Hypoplasia of the 5th finger
Absent/small little finger
Absent/small pinkie finger
Absent/small pinky finger
Absent/underdeveloped little finger
Absent/underdeveloped pinkie finger
Absent/underdeveloped pinky finger

[ more ]

0006262
Aplasia/hypoplasia of the femur
Absent/small thighbone
Absent/underdeveloped thighbone

[ more ]

0005613
Congenital hip dislocation
Dislocated hip since birth
0001374
Foot oligodactyly
Missing toes
0001849
Hand oligodactyly
Hand has less than 5 fingers
0001180
Hypoplastic iliac wing
0002866
Hypoplastic pelvis
0008839
Patellar aplasia
Absent kneecap
0006443
Postaxial hand polydactyly
Extra little finger
Extra pinkie finger
Extra pinky finger

[ more ]

0001162
Short stature
Decreased body height
Small stature

[ more ]

0004322
Talipes equinovarus
Club feet
Club foot
Clubfeet
Clubfoot

[ more ]

0001762
Toe syndactyly
Fused toes
Webbed toes

[ more ]

0001770
Ulnar deviation of finger
Finger bends toward pinky
0009465
5%-29% of people have these symptoms
Finger syndactyly
0006101
Percent of people who have these symptoms is not available through HPO
Absent toenail
0001802
Amenorrhea
Abnormal absence of menstruation
0000141
Aplasia/Hypoplasia of the phalanges of the hand
0009767
Autosomal recessive inheritance
0000007
Clinodactyly
Permanent curving of the finger
0030084
Fibular aplasia
Absent calf bone
0002990

Cause

Fuhrmann syndrome is caused by changes (mutations) in the WNT7A gene. This gene is responsible for controlling the development of the hands and feet.[3] When there is a mutation in the WNT7A gene, this gene cannot work properly, which causes the signs and symptoms associated with the syndrome.[3]

Fuhrmann syndrome is very similar to another syndrome known as Al-Awadi-Raas-Rothschild syndrome. However, the genetic mutations that cause Fuhrmann syndrome only result in partial loss of the function of the gene. The genetic mutations that cause Al-Awadi-Raas-Rothschild syndrome result in complete loss of function of the gene.Therefore, the symptoms associated with Fuhrmann syndrome tend to be more mild than those associated with Al-Awadi-Raas-Rothschild syndrome.[6]

Diagnosis

A diagnosis of Fuhrmann syndrome can be made when a doctor observes signs and symptoms consistent with the syndrome.[3] Diagnosis can be confirmed by genetic testing that finds two changes in the WNT7A  gene

Another syndrome called Al-Awadi-Raas-Rothschild syndrome is also caused by mutations to the WNT7A gene. In some cases, the exact same genetic change can cause one syndrome in one person and the other syndrome in another person. Therefore, diagnosis of these syndromes should be made based on the clinical features of each individual person.[6]

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

    The treatment recommended for people affected by Fuhrmann syndrome will depend on the signs and symptoms present in each person. Some of the skeletal changes associated with Fuhrmann syndrome may be corrected with surgery. However, there are not surgeries available for all of the signs and symptoms associated with Fuhrmann syndrome.[4]

    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.

      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 Fuhrmann syndrome. Click on the link to view a sample search on this topic.

        References

        1. Fibular aplasia or hypoplasia, femoral bowing and poly-, syn-, and oligodactyly. Online Mendelian Inheritance in Man. May 23, 2016; https://www.omim.org/entry/228930.
        2. Fuhrmann syndrome. Orphanet. September 2006; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Expert=2854.
        3. Al-Qattan MM, Shamseldin HE, and Alkuraya FS. The WNT7A G204S mutation is associated with both Al-Awadi-Raas Rothschild syndrome and Fuhrmann syndrome phenotypes. Gene. March 1, 2013; 516(1):168-170. https://www.ncbi.nlm.nih.gov/pubmed/23266637.
        4. Mukhtar K, Matuszczak M, and Bermejo-Sanchez E. Anesthesia recommendations for patients suffering from phocomelia. Orphan Anesthesia. November 2013; https://www.orpha.net/data/patho/Pro/en/Phocomelia-En.pdf.
        5. Woods CG, Stricker S, Seemann P, Stern R, Cox J, Sherridan E, Roberts E, Springell K, Scott S, Karbani G, Sharif SM, Toomes C, Bond J, Kumar D, Al-Gazili L, and Mundlos S. Mutations in WNT7A cause a range of limb malformations, including Fuhrmann syndrome and Al-Awadi/Raas-Rothschild/Schinzel Phocomelia syndrome. American Journal of Human Genetics. August 2006; 79(2):402-408. https://www.cell.com/ajhg/fulltext/S0002-9297(07)63150-4.
        6. Al-Qattan MM. Molecular basis of the clinical features of Al-Awadi-Raas-Rothschild (limb/pelvis/uterus-hypoplasia/aplasia) syndrome (AARRS) and Fuhrmann syndrome.. American Journal of Medical Genetics. September 2013; 161A(9):2274-2280. https://www.ncbi.nlm.nih.gov/pubmed/23922166.