Marsili syndrome

Marsili syndrome, also known as MARSIS, is an extremely rare genetic disorder characterized by symptoms similar to those reported in individuals with congenital insensitivity to pain [1]. It is an autosomal dominant pain insensitivity disorder, which means that a single copy of the mutated gene is enough to cause the condition [2][3].

Individuals with Marsili syndrome have a lowered ability to sense pain, experience temperature, and sweat. This can lead to difficulties in detecting and responding to painful stimuli, as well as other sensory-related issues [4]. The mutation responsible for this condition affects the ZFHX2 gene, which plays a crucial role in regulating various physiological processes [5].

It's worth noting that Marsili syndrome is considered a benign disease with a good prognosis. A definitive diagnosis can help avoid ineffective treatment and its associated complications [6].

Marsili Syndrome Signs and Symptoms

Marsili syndrome, also known as Congenital Insensitivity to Pain with Anhidrosis (CIPA), is a rare genetic disorder characterized by a lack of sensitivity to pain. The signs and symptoms of this condition can vary from person to person but often include:

• Reduced or absent pain sensation: People with Marsili syndrome may not feel pain, even in situations where it would normally be expected, such as broken bones or burns.
• Temperature insensitivity: Affected individuals may not be able to sense temperature extremes, such as hot or cold.
• Anhidrosis: Some people with Marsili syndrome may experience a lack of sweating, which can make them more susceptible to heat-related illnesses.
• Painless injuries: Individuals with this condition may not feel pain when they are injured, which can lead to unnoticed and untreated injuries.
• Fragility and fractures: As seen in the case of Ludovico Marsili (son of Letizia Marsili), individuals with Marsili syndrome may experience fragility and fractures due to their inability to sense pain.

It's essential to note that while people with Marsili syndrome may not feel pain, they can still experience other sensations, such as touch, pressure, or visceral pain (e.g., during childbirth). However, the severity of these symptoms can vary greatly from person to person.

References:

• [1] Amromin describes a 2-generation family with symptoms characteristic of Marsili syndrome.
• [3] People with this condition can feel the difference between sharp and dull but cannot sense pain.
• [5] Marsili syndrome is characterized by severe signs and symptoms of HSAN5.
• [13] Affected individuals do not perceive broken bones and burns as painful, and have lowered sensitivity to capsaicin.

Marsili syndrome, also known as congenital insensitivity to pain, is a rare genetic disorder that affects an individual's ability to perceive physical pain. Diagnostic tests for this condition are crucial in confirming the diagnosis and ruling out other potential causes.

Electrophysiologic studies: These tests measure the electrical activity of the nervous system and can help identify abnormalities in nerve function [12]. Skin biopsy, whole exome sequencing, animal behavior tests, and in vivo electrophysiology are some of the diagnostic tests used to study this condition [13].

Diagnostic tests for Marsili syndrome: The following tests may be used to diagnose Marsili syndrome:

• Electrophysiologic studies: These tests can help identify abnormalities in nerve function.
• Skin biopsy: This test involves taking a sample of skin tissue to examine for any abnormalities.
• Whole exome sequencing: This genetic test analyzes the entire genome to identify any mutations that may be causing the condition.
• Animal behavior tests: These tests assess an individual's ability to perceive pain and respond accordingly.
• In vivo electrophysiology: This test measures the electrical activity of the nervous system in real-time.

Other diagnostic tests: The following tests may also be used to diagnose Marsili syndrome:

• Clinical trials: Participating in clinical trials can provide access to new and innovative treatments for this condition.
• Biobanks: These are collections of biological samples that can be used for research purposes.
• Patient registries: These registries collect data on individuals with specific conditions, including Marsili syndrome.

Genetic tests: Genetic tests may also be used to diagnose Marsili syndrome. These tests can identify any genetic mutations that may be causing the condition [10].

Please note that these diagnostic tests are not exhaustive and may vary depending on individual circumstances. It's essential to consult a healthcare professional for accurate diagnosis and treatment options.

References: [10] - Genetic Tests for Marsili Syndrome. [12] - Diagnostic tests. Laboratories · Diagnostic tests. Research and trials. Research project(s) · Clinical trial(s) · Biobanks · Patient registries · Platforms. [13] - by AM Habib · 2018 · Cited by 53 — Study subjects · Sensory phenotype assessment methods · Skin biopsy · Whole exome sequencing · Animal behaviour tests · In vivo electrophysiology.

Current Status of Drug Treatment for Marsili Syndrome

Marsili syndrome, a rare genetic disorder characterized by pain insensitivity, temperature insensitivity, and reduced sweating, has no effective genetic therapy available as of 2022 [4]. Researchers are actively seeking treatments for chronic pain associated with this condition.

Potential Therapeutic Approaches

One possible treatment strategy is gene therapy, which aims to mimic the specific gene mutation causing pain insensitivity in individuals with Marsili syndrome [7][8]. This approach involves overexpressing the mutated gene to replicate the phenotype. However, more research is needed to explore the feasibility and effectiveness of this method.

Challenges and Future Directions

The development of effective treatments for Marsili syndrome faces significant challenges due to its rarity and the complexity of the underlying genetic mutation [4][9]. Further studies are required to identify potential drug targets that could lead to improved treatment options for individuals with this condition.

References:

• [4] To our knowledge, there is currently no effective genetic therapy for this disease.
• [7] "One possible treatment may be a gene therapy strategy, if we could find a way to mimic the Marsili phenotype by overexpressing the mutated ...
• [8] Scientists have identified a mysterious genetic mutation that effectively negates the sensation of pain, enabling people with the rare anomaly ...
• [9] ... treatment of chronic pain. Keywords: pain ... It was called Marsili syndrome, from the name of the family. ... drug targets that could lead to ...

Marsili syndrome, also known as MARSIS, is an autosomal dominant pain insensitivity disorder characterized by a lowered ability to sense pain, temperature, and sweat. When considering the differential diagnosis for Marsili syndrome, several conditions should be taken into account.

• Familial amyloidotic polyneuropathy: This is a rare genetic disorder that affects the nerves and can cause pain insensitivity, among other symptoms [3].
• Fabry disease: Another rare genetic disorder that can cause pain insensitivity, as well as other systemic symptoms [3].
• Neuropathic osteoarthropathy: A condition characterized by joint and bone abnormalities, which can be associated with pain insensitivity in some cases [1].
• Congenital insensitivity to pain with anhidrosis: A rare genetic disorder that is similar to Marsili syndrome in its symptoms, including pain insensitivity and lack of sweating [10].

It's worth noting that the differential diagnosis for Marsili syndrome can be challenging due to the rarity of the condition. However, a comprehensive diagnostic panel, such as the one described in [6], can help guide the diagnostic process.

In addition, genetic testing may be necessary to confirm the diagnosis of Marsili syndrome, particularly if there is a family history of the condition [11].

References: [1] Neuropathic osteoarthropathy: diagnostic dilemmas and differential diagnosis. [3] by JJ Cox · 2020 · Cited by 5 — In the differential diagnosis particularly two monogenic pain disorders, i. e., familial amyloidotic polyneuropathy and Fabry disease, have ... [6] Comprehensive differential diagnostic panel for Neuropathy, hereditary sensory and autonomic type 2 comprising 18 guideline-curated and altogether 20 ... [10] Marsili syndrome is an extremely rare genetic disorder which is characterized by symptoms similar to those reported on individuals with congenital insensitivity to pain with anhidrosis. [11] Conclusions: Marsili syndrome is an autosomal dominant genetic disease. It is extremely rare worldwide. In clinical practice, when a patient presents with unexplained recurrent fever and poor effect of non-steroidal anti-inflammatory drugs, especially with the symptoms of no sweating and insensitivity to pain, the possibility of Marsili ...