Medicine:Du Pan syndrome
| Du Pan syndrome | |
|---|---|
| Other names | Fibular hypoplasia and complex brachydactyly |
 | |
| Radiograph of the hands of an Egyptian patient with Du Pan syndrome | |
| Specialty | Medical genetics |
| Symptoms | Complicated brachydactyly and dysplastic/aplastic/hypoplastic fibula bones and hands and feet |
| Complications | Balance |
| Usual onset | Birth |
| Duration | Life-long |
| Causes | Genetic mutation |
| Risk factors | Being born to consanguineous parents or having a parent with the disorder |
| Diagnostic method | Through symptoms and molecular testing |
| Prevention | none |
| Prognosis | Good |
| Frequency | very rare, around 30 cases have been reported. |
Du Pan syndrome, also known as fibular aplasia-complex brachydactyly syndrome, is an extremely rare genetic condition. Unlike other rare genetic conditions, Du Pan syndrome does not affect brain function or the appearance of the head and trunk. This condition is associated with alterations to the GDF5 (also known as CDMP1) gene [1].The way that this condition is passed on from generation to generation varies, but it is most commonly inherited in an autosomal recessive manner, meaning two copies of the same version of the gene are required to show this condition.[2] Rare cases exist where the mode of inheritance is autosomal dominant, which means only one version of the gene is necessary to have the condition.[2]
Symptoms
Du Pan Syndrome is a form of Acromesomelic Dysplasia, which is a condition that affects bone growth. It is characterized by the incomplete development of the fibula, resulting in under-developed hands and feet and shorter fingers and toes. However, the development in other aspects of the body and mind is not affected. The impacted extremities will appear disproportionally smaller in comparison to the rest of their body.[1] They often describe the toes and fingers to appear “ball-like,” as they are missing the length between the foot and the ends of the toes, or the hand and the ends of the fingers.[3]
Diagnosis
Until April 2023, fewer than 30 people worldwide had been diagnosed with Du Pan syndrome.[3] The primary diagnosis of the syndrome largely depends on its clinical symptoms, including short or completely missing leg bones and ball-like shaped toes and fingers. Molecular confirmation of the syndrome utilizes genetic testing for alterations in the cartilage-derived morphogenetic protein-1 gene (GDF5).[4] This method is often used as a complementary tool for diagnosis, and only 5 of all diagnosed Du Pan syndrome patients were molecularly confirmed due to technological limitations before the 2000s.
The first prenatally diagnosed case of Du Pan syndrome was found using a combination of ultrasound imaging and gene sequencing, which identify the DNA sequence of both the fetus and the mother.[5]
Treatments
There is no current cure for Du Pan and treatments primarily focus on managing the associated symptoms and improving the individual's quality of life. The management of this condition often involves a multidisciplinary approach, with medical professionals, orthopedic specialists, and physical therapists working together.
Orthopedic interventions may include surgical procedures to correct bone position, limb length conditions, or joint issues, which can help improve mobility and reduce pain. Physical therapy and rehabilitation are often recommended to enhance muscle strength, joint flexibility, and overall physical functionAssistive devices such as braces, crutches, or wheelchairs may be used to promote mobility and comfort.
Pain management is an essential aspect of care, and medications or other therapies may be prescribed to alleviate discomfort.[6] Additionally, genetic counseling can provide families with information about the condition's inheritance patterns and guide family planning decisions.[7]
Current research is more focused on Acromesomelic Dysplasia and is being studied in Boston Children Hospital.[8]
Similar Syndromes
Other Acromesomelic Dysplasia sharing similar symptoms with Du Pan syndrome include Hunter–Thompson dysplasia and Grebe dysplasia.
Symptoms of Hunter–Thompson dysplasia include increased and more frequent joint differences, like dislocated hips, knees, radial heads, and underdeveloped thigh bone protrusion (femoral condyle) when comparing to Du Pan syndrome. Additionally, there are minor differences in the pattern of short supporting bone in the hands and feet.
Individuals with Grebe dysplasia typically have a considerably shorter stature, particularly the femurs and tibias. Moreover, there is a marked and consistent reduction in size observed in the smaller tubular bones of the hands and feet.
Commonalities among all these conditions lie in genetic variations affecting GDF5. Carriers with two copies of mutated GDF5 usually develop into Grebe dysplasia, while carriers with only one copy may exhibit relatively milder symptoms and Hunter–Thompson dysplasia and Du Pan syndrome.[9]
References
- ↑ 1.0 1.1 Szczaluba, K.; Hilbert, K.; Obersztyn, E.; Zabel, B.; Mazurczak, T.; Kozlowski, K.. "Du Pan syndrome phenotype caused by heterozygous pathogenic mutations in CDMP1 gene" (in en). American Journal of Medical Genetics Part A 138A (4): 379–383. doi:10.1002/ajmg.a.30969. ISSN 1552-4825. https://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.30969.
- ↑ 2.0 2.1 "Autosomal Recessive Disorder". November 20, 2023. https://www.genome.gov/genetics-glossary/Autosomal-Recessive-Disorder#:~:text=Autosomal%20recessive%20is%20a%20pattern,required%20to%20cause%20the%20disorder..
- ↑ 3.0 3.1 Turgut, G. Tutku; Kalelioglu, Ibrahim Halil; Karaman, Volkan; Sarac Sivrikoz, Tugba; Karaman, Birsen; Uyguner, Zehra Oya; Kalayci, Tugba (2023-04-20). "Fibular Agenesis and Ball-Like Toes Mimicking Preaxial Polydactyly: Prenatal Presentation of Du Pan Syndrome". Molecular Syndromology 14 (2): 152–157. doi:10.1159/000527955. ISSN 1661-8769. PMC 10091002. https://doi.org/10.1159/000527955.
- ↑ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Fibular aplasia complex brachydactyly syndrome" (in en). https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2639.
- ↑ Turgut, G. Tutku; Kalelioglu, Ibrahim Halil; Karaman, Volkan; Sarac Sivrikoz, Tugba; Karaman, Birsen; Uyguner, Zehra Oya; Kalayci, Tugba (2023-04-20). "Fibular Agenesis and Ball-Like Toes Mimicking Preaxial Polydactyly: Prenatal Presentation of Du Pan Syndrome". Molecular Syndromology 14 (2): 152–157. doi:10.1159/000527955. ISSN 1661-8769. PMC 10091002. https://doi.org/10.1159/000527955.
- ↑ "Acromesomelic Dysplasia - Symptoms, Causes, Treatment | NORD" (in es-ES). https://rarediseases.org/es/rare-diseases/acromesomelic-dysplasia/.
- ↑ "Fibular Agenesis and Ball-Like Toes Mimicking Preaxial Polydactyly: Prenatal Presentation of Du Pan Syndrome". https://karger.com/msy/article/14/2/152/835549/Fibular-Agenesis-and-Ball-Like-Toes-Mimicking.
- ↑ "Acromesomelic Dysplasia | Research Focus Areas | Center for the Study of Genetic Skeletal Disorders Research | Research Centers | Research | Boston Children's Hospital". https://www.childrenshospital.org/research/centers/center-study-genetic-skeletal-disorders-research/research-focus-areas/acromesomelic-dysplasia.
- ↑ Szczaluba, K.; Hilbert, K.; Obersztyn, E.; Zabel, B.; Mazurczak, T.; Kozlowski, K. (2005). "Du Pan syndrome phenotype caused by heterozygous pathogenic mutations in CDMP1 gene". American Journal of Medical Genetics Part A 138A (4): 379–383. doi:10.1002/ajmg.a.30969. ISSN 1552-4825. https://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.30969.
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