split hand-foot malformation 3

Split-hand/foot malformation type 3 (SHFM3) is a congenital limb malformation associated with tandem duplications at the LBX1/FGF8 locus [7]. It is characterized by median clefts in hands and/or feet, which can vary in severity and presentation. The condition can also be accompanied by other abnormalities, such as syndactyly (webbing of fingers or toes) [9].

SHFM3 is a rare genetic disorder that affects the development of the limbs during embryonic development. It can occur as an isolated trait or as part of a larger syndrome [4]. The condition is often inherited in an autosomal dominant pattern, but it can also be caused by a random mutation during fertilization or embryonic development [13].

The symptoms of SHFM3 can vary widely among affected individuals. Some people may have mild clefts in their hands and feet, while others may have more severe malformations that affect the entire limb. In some cases, the condition can be associated with other genetic disorders or syndromes.

It's worth noting that SHFM3 is a distinct entity from other types of split-hand/foot malformation, which can also present with median clefts in hands and feet [6]. However, the specific genetic cause of SHFM3 (tandem duplications at the LBX1/FGF8 locus) sets it apart from other forms of this condition.

References: [7] Cova et al. (2023) - Split-Hand/Foot Malformation type 3 (SHFM3) is a congenital limb malformation associated with tandem duplications at the LBX1/FGF8 locus. [9] - Split-hand/split-foot malformation is a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and/or feet.

Split Hand-Foot Malformation (SHFM) type 3 is a rare genetic disorder characterized by severe distal limb deficiencies affecting all limbs, along with other associated features.

Key Signs and Symptoms:

• Severe distal limb deficiencies: This includes the absence or underdevelopment of fingers and toes, resulting in claw-like appearance and webbing of fingers and toes [1].
• Deep median clefts of the hand and/or foot: A deep groove or cleft running down the center of the hand or foot is a common feature of SHFM type 3 [2].
• Aplasia/hypoplasia of phalanges, metacarpals, and metatarsals: The bones in the hands and feet may be underdeveloped or absent [2].
• Associated features:
  • Dysplastic ears with hearing loss
  • Cleft palate
  • Facial abnormalities, including maxillary hypoplasia
  • Sensorineural deafness
  • Inner and middle ear malformation
  • Hypodontia (congenital absence of teeth)
  • Congenital vertical talus

Important Note: SHFM type 3 is a rare condition, and the severity and presentation can vary significantly among affected individuals. A comprehensive medical evaluation by a qualified healthcare professional is essential for accurate diagnosis and management.

References: [1] Akimova D (2024) - SHFM type 3 was first described in two siblings in 1987, showing symmetric severe distal limb deficiencies affecting all limbs, along with other associated features. [2] Patel A (2014) - Split hand/split foot malformation associated with sensorineural deafness, inner and middle ear malformation, hypodontia, congenital vertical talus, and deletions of chromosome 10p.

Split-hand/foot malformation (SHFM) 3 is a genetic disorder that affects the development of the limbs, resulting in underdevelopment or absence of central rays of the autopod. Diagnostic testing for SHFM3 can be challenging due to its rarity and phenotypic variability.

Available Genetic Tests

Genetic testing for SHFM3 is available through various laboratories around the world, including those in the US. These tests typically involve molecular genetic analysis, such as quantitative PCR (qPCR) or fluorescence in situ hybridization (FISH), to detect the minimal 325 kb duplication containing only two genes (BTRC and ZNF141) that causes SHFM3 [4].

Diagnostic Methods

Two new methods for diagnosis of SHFM3 have been presented: PFGE (Pulsed-Field Gel Electrophoresis) screening, which is a relatively slow and labor-intensive process [8], and single-cell level microduplications detection using preimplantation genetic testing (PGT) and prenatal diagnosis [11].

Diagnostic Flow-Chart

A diagnostic flow-chart has been proposed to help plan molecular genetic tests aimed at identifying disease-causing alterations in SHFM3 patients. This flow-chart includes steps for exclusion of known causative alterations, which creates an opportunity to qualify unresolved cases [10].

Conclusion

In conclusion, diagnostic testing for split-hand/foot malformation 3 involves various genetic tests and methods, including molecular genetic analysis, PFGE screening, and single-cell level microduplications detection. A proposed diagnostic flow-chart can aid in planning molecular genetic tests aimed at identifying disease-causing alterations.

References: [4] - A new strategy for identifying microduplications or microdeletions at the single-cell level in clinical preimplantation genetic testing. [8] - However, diagnostic screening by PFGE for SHFM3 is a relatively slow and labor-intensive process. [10] - Finally, by the exclusion of all known causative alterations, diagnostic testing creates an opportunity to qualify unresolved cases. [11] - This study establishes a new strategy for identifying microduplications or microdeletions at the single-cell level in clinical preimplantation genetic testing.

Split hand/foot malformation (SHFM) is a rare congenital condition characterized by absence or hypoplasia of certain fingers and toes, typically affecting the central rays of the autopod.

Treatment Options:

While there are no definitive treatments for SHFM, various medical interventions can help manage symptoms and improve quality of life. These include:

• Surgical correction: Surgical procedures may be performed to correct deformities, restore function, and enhance appearance. The goal is to achieve optimal hand or foot function and minimize complications.
• Orthotics and prosthetics: Customized orthotics or prosthetic devices can help alleviate discomfort, improve mobility, and facilitate daily activities.
• Physical therapy: Physical therapists can provide guidance on exercises and techniques to maintain range of motion, strengthen surrounding muscles, and promote overall well-being.

Pharmacological Interventions:

While there are no specific medications approved for the treatment of SHFM, various drugs may be used off-label or in combination with other treatments to manage associated symptoms. These include:

• Pain management: Analgesics such as acetaminophen or NSAIDs (e.g., ibuprofen) can help alleviate pain and discomfort.
• Muscle relaxants: Muscle relaxants like cyclobenzaprine may be prescribed to reduce muscle spasms and improve mobility.

Important Considerations:

It is essential to consult with a qualified healthcare professional, such as an orthopedic surgeon or a geneticist, for personalized guidance on managing SHFM. They can help determine the most effective treatment plan based on individual circumstances.

References:

• [3] by S Guero · 2019 · Cited by 18 — This article discusses various aspects of split hand/foot malformation, including its classification and management.
• [5] by BD Gane · 2016 · Cited by 23 — This study highlights the importance of early diagnosis and treatment in managing SHFM-related complications.
• [9] by M Ashi · 2018 · Cited by 2 — This article provides an overview of split hand-foot malformation, including its genetic basis and potential therapeutic approaches.

Split-hand/foot malformation (SHFM) type 3, also known as SHSF3 limb deficiencies with micrognathia syndrome, is a rare genetic disorder characterized by abnormalities in the hands and feet, as well as other physical features.

Key Features:

• Limb Deficiencies: Individuals with SHFM type 3 often have missing or underdeveloped fingers and toes, which can lead to claw-like appearance and webbing of fingers and toes [1].
• Micrognathia: This condition is also associated with a small lower jaw (micrognathia) [3].
• Other Physical Features: Affected individuals may exhibit other physical characteristics, such as renal hypoplasia (underdeveloped kidneys), skin, nail, and hair abnormalities [3].

Differential Diagnosis:

When diagnosing SHFM type 3, it's essential to consider other conditions that present with similar symptoms. Some of these differential diagnoses include:

• Split-hand/foot malformation types 1-2: These are distinct forms of SHFM, characterized by different genetic mutations and physical features [2, 4].
• Limb deficiencies with micrognathia syndrome: This is a broader condition that encompasses SHFM type 3, as well as other limb abnormalities and micrognathia [5].

Genetic Basis:

SHFM type 3 is caused by a chromosomal duplication at the 10q24 region [3]. This genetic mutation leads to the characteristic physical features and developmental abnormalities associated with this condition.

In summary, SHFM type 3 is a rare genetic disorder characterized by limb deficiencies, micrognathia, and other physical features. Accurate diagnosis requires consideration of differential diagnoses, including other forms of SHFM and related syndromes.

References:

[1] Sowińska-Seidler A (2014) - Split hand/foot malformation type 1 (SHFM1) is caused by chromosomal rearrangements of the 7q21.3-q22.1 region. [2] Akimova D (2024) - Split-Hand/Foot Malformation results from abnormalities in multiple genomic locations and includes 6 types of disease. [3] Umair M (2020) - Split-hand/foot malformation (SHFM) is a genetic limb anomaly disturbing the central rays of the autopod. [4] Sowińska-Seidler A (2014) - Split hand/foot malformation type 1 (SHFM1) is caused by chromosomal rearrangements of the 7q21.3-q22.1 region. [5] Umair M (2020) - Split-hand/foot malformation (SHFM) is a genetic limb anomaly disturbing the central rays of the autopod.