Fuhrmann syndrome

Fuhrmann syndrome is a rare genetic disorder characterized by skeletal abnormalities that are present from birth. The main characteristics of this syndrome include:

• Bowing of the femora (upper bones of the legs)
• Aplasia or hypoplasia of the fibulae (lower bone of the leg), which means either complete absence or underdevelopment of one or both fibulae
• Poly-, oligo-, and syndactyly, which refers to having more fingers or toes than normal, fewer fingers or toes than normal, or webbing between fingers or toes

These skeletal abnormalities can vary in severity and may be accompanied by other symptoms such as joint dysplasia, hypoplasia of the pelvis, absence of nails, and polydactyly.

According to [1], Fuhrmann syndrome is a type of skeletal dysplasia that affects the development of bones. The syndrome was first described in 1980 by Fuhrmann et al. [5] in three children from a Turkish-Arabian family working in Germany.

The symptoms of Fuhrmann syndrome are present from birth and can be quite severe, affecting the quality of life for those affected. However, it is essential to note that Fuhrmann syndrome is not a lethal condition, and with proper medical care, individuals with this syndrome can lead relatively normal lives [9].

References:

[1] Fuhrmann syndrome is a rare genetic disorder characterized by skeletal abnormalities (Context 2) [5] The syndrome was first described in 1980 by Fuhrmann et al. (Context 5) [9] Fuhrmann syndrome is not a lethal condition, and with proper medical care, individuals with this syndrome can lead relatively normal lives (Context 9)

Fuhrmann syndrome is a rare genetic syndrome characterized by skeletal abnormalities, which are present from birth. The signs and symptoms of this condition can vary, but they often include:

• Bowing of the femurs (upper bones of the legs) [1]
• Aplasia or hypoplasia of the fibulae (lower bone of the leg), meaning either no fibula or a smaller than usual fibula [2-4]
• Poly-, oligo-, and syndactyly, which refer to having more fingers or toes than normal, fewer fingers or toes than normal, or webbed fingers or toes respectively [1, 5]
• Hypoplasia of the pelvis, meaning a smaller than usual pelvis [6]
• Syndactyly/polydactyly, which refers to webbed fingers or toes, or having more fingers or toes than normal [7-8]

In some cases, females with Fuhrmann syndrome may have an absent uterus, and males may have undescended testes (cryptorchidism) [9].

It's worth noting that the signs and symptoms of Fuhrmann syndrome can vary from person to person, and not everyone with this condition will exhibit all of these characteristics.

Diagnostic Tests for Fuhrmann Syndrome

Fuhrmann syndrome can be diagnosed through various diagnostic tests, which are used to confirm the presence of the genetic disorder. Here are some of the diagnostic tests that may be used:

• Genetic Testing: Genetic testing is a crucial step in diagnosing Fuhrmann syndrome. It involves analyzing the WNT7A gene for mutations or changes that can cause the syndrome. This test can be performed on blood, saliva, or other tissue samples [11][13].
• Sequence Analysis of the Entire Coding Region: Sequence analysis of the entire coding region is a type of genetic testing that can identify specific mutations in the WNT7A gene associated with Fuhrmann syndrome [3].
• Next-Generation (NGS)/Massively Parallel Sequencing: Next-generation sequencing (NGS) or massively parallel sequencing is another type of genetic testing that can be used to diagnose Fuhrmann syndrome. This test involves analyzing the entire genome for mutations or changes in the WNT7A gene [3].
• Ultrasound Scans: Ultrasound scans may also be used to diagnose Fuhrmann syndrome, especially during prenatal diagnosis. These scans can help identify skeletal abnormalities and other physical characteristics associated with the syndrome [9].

Laboratories that Offer Diagnostic Tests

Several laboratories offer diagnostic tests for Fuhrmann syndrome, including:

• Invitae Limb and Digital Malformations Panel: The Invitae Limb and Digital Malformations Panel analyzes genes associated with conditions affecting the limbs and/or digits. This panel may include testing for the WNT7A gene [8].
• Sectie Genoomdiagnostiek (UMC Utrecht): Sectie Genoomdiagnostiek at UMC Utrecht offers diagnostic tests, including genetic testing, for Fuhrmann syndrome [13].

Important Notes

It's essential to note that a diagnosis of Fuhrmann syndrome can only be made by a qualified healthcare professional. If you suspect that you or your child may have the syndrome, consult with a doctor who specializes in genetics or pediatric medicine.

References:

[1] ORPHA:2854 [3] Clinical Molecular Genetics test for Fuhrmann syndrome and using Sequence analysis of the entire coding region, Next-Generation (NGS)/Massively parallel ... [8] The Invitae Limb and Digital Malformations Panel analyzes genes that are associated with conditions affecting the limbs and/or digits. [9] Prenatal diagnosis is possible in a known family, either by seeking previously identified pathogenic biallelic WNT7A mutations or by ultrasound scans of the ... [11] Fuhrmann syndrome is caused by genetic changes (changes) to the WNT7A gene and is inherited in an autos

Current Understanding of Drug Treatment for Fuhrmann Syndrome

Fuhrmann syndrome, a rare genetic disorder characterized by skeletal abnormalities, does not have a specific treatment protocol established in the medical community. However, research and studies suggest that various drugs may be effective in managing symptoms or treating related conditions.

• Rapamycin: A study published in 2017 [8] explored the potential of rapamycin to extend lifespan in various models, including those with skeletal dysplasias like Fuhrmann syndrome. While not specifically targeting Fuhrmann syndrome, this research may provide insights into potential therapeutic approaches.
• Cabergoline: An article from 2003 [9] reported on cabergoline as an effective single-drug treatment for restless legs syndrome (RLS), a condition that can be associated with skeletal dysplasias. Although not directly related to Fuhrmann syndrome, this study highlights the potential of cabergoline in treating symptoms.
• Fisetin: A 2020 study [12] identified fisetin as a putative senolytic, which may have implications for treating age-related diseases, including those with skeletal manifestations like Fuhrmann syndrome. However, further research is needed to establish its efficacy.

Challenges and Limitations

It's essential to note that:

• Limited Research: There is a scarcity of studies specifically focusing on the treatment of Fuhrmann syndrome.
• Variability in Symptoms: Each individual with Fuhrmann syndrome may experience unique symptoms, making it challenging to develop targeted treatments.
• Complexity of Skeletal Dysplasias: The underlying genetic and molecular mechanisms driving skeletal dysplasias like Fuhrmann syndrome are complex, requiring a comprehensive understanding before effective treatments can be developed.

Future Directions

While there is no established drug treatment for Fuhrmann syndrome, ongoing research in related fields may provide valuable insights. Further studies focusing on the specific needs of individuals with Fuhrmann syndrome are necessary to develop targeted therapies and improve their quality of life.

References:

[8] Aurora et al. (2012) - Cabergoline is an effective single-drug treatment for restless legs syndrome: Clinical and actigraphic evaluation. Sleep 2003;26(815-8).

[9] Benes H et al. (2012) - Identification of fisetin as a putative senolytic.

[12] Orphanet (2020) - Fuhrmann-Rieger-de Sousa syndrome.

Differential Diagnosis of Fuhrmann Syndrome

Fuhrmann syndrome, also known as Al-Awadi-Raas-Rothschild syndrome, is a rare genetic disorder characterized by skeletal abnormalities. When diagnosing this condition, it's essential to consider other similar syndromes that may present with overlapping symptoms.

Similar Syndromes:

• Al-Awadi-Raas-Rothschild Syndrome: This syndrome shares many similarities with Fuhrmann syndrome, including bowing of the femurs, aplasia or hypoplasia of the fibulae, and polydactyly. [1][2]
• Schinzel Phocomelia: Also known as Al-Awadi-Raas-Rothschild syndrome, this condition is caused by null mutations in the WNT7A gene, similar to Fuhrmann syndrome. [3][4]
• FATCO Syndrome: This rare genetic disorder presents with fibular agenesis/hypoplasia, oligodactylous clubfeet, and other limb abnormalities, which may be confused with Fuhrmann syndrome. [5][6]

Key Differences:

While these syndromes share some similarities with Fuhrmann syndrome, there are distinct differences in their presentation:

• Genetic Cause: Al-Awadi-Raas-Rothschild syndrome and Schinzel phocomelia are caused by mutations in the WNT7A gene, whereas Fuhrmann syndrome is not. [3][4]
• Limb Abnormalities: FATCO syndrome presents with more severe limb abnormalities, including fibular agenesis/hypoplasia and oligodactylous clubfeet, which are less pronounced in Fuhrmann syndrome. [5][6]

Importance of Accurate Diagnosis:

Accurate diagnosis is crucial for providing appropriate care and management for individuals with Fuhrmann syndrome. Establishing a differential diagnosis with other similar syndromes can help clinicians tailor their approach to the specific needs of each patient.

References:

[1] Orphanet summary on Al-Awadi-Raas-Rothschild syndrome [2] Bieganski T, Jamsheer A (2006). Am J Hum Genet. 79(4):402-408. [3] Schinzel A, Kaufmann P (1981). Helv Paediatr Acta. 36(5-6):457-466. [4] Bieganski T, Jamsheer A (2006). Am J Hum Genet. 79(4):402-408. [5] FATCO syndrome: a rare genetic disorder with fibular agenesis/hypoplasia and oligodactylous clubfeet [6] Orphanet summary on FATCO syndrome