Proteus syndrome

Proteus Syndrome: A Rare Condition Characterized by Overgrowth

Proteus syndrome is a rare and complex condition characterized by the overgrowth of various tissues in the body, including skin, bones, fatty tissues, and blood vessels. This condition can manifest at birth or develop later in life, with symptoms varying from person to person.

Key Features:

• Overgrowth: Proteus syndrome is marked by progressive and abnormal growth of body tissues, leading to asymmetrical limb, digital, or cranial overgrowth.
• Disproportionate Growth: The condition often results in disproportionate growth of limbs, hands, feet, or other body parts.
• Multiple Hamartomas: Proteus syndrome can also involve the development of multiple hamartomas, which are benign tumors composed of various types of tissue.

Causes and Risk Factors:

• Genetic Background: Proteus syndrome is believed to have a genetic background, with mutations in certain genes contributing to its development.
• Mosaic Variant: The condition often results from a mosaic variant, where some cells in the body contain the mutated gene while others do not.

Symptoms and Signs:

• Asymmetrical Limb Overgrowth: One of the most common symptoms is asymmetrical limb overgrowth, which can affect hands, feet, or other body parts.
• Skin and Tissue Overgrowth: The condition can also involve the overgrowth of skin, fatty tissues, and blood vessels.
• Vascular Malformations: Proteus syndrome may be associated with vascular malformations, such as hemangiomas.

References:

• [1] Proteus syndrome is a rare condition characterized by overgrowth of the bones, skin, and other tissues. Organs and tissues affected by the ...
• [2] Proteus syndrome is a rare disorder characterized by overgrowth of various tissues of the body.
• [3] Proteus syndrome is a rare syndrome characterized by disproportionate overgrowth of limbs, multiple hamartomas, and vascular malformations.
• [4] Signs and symptoms of Proteus syndrome include asymmetrical limb, digital, or cranial overgrowth when present at birth.
• [5] It is characterized by the progressive and abnormal growth of body tissues, including skin, bones, fatty tissues and blood vessels.
• [6] Proteus syndrome results from assymetric and patchy overgrowth of various tissues including bones and connective tissues.
• [7] This often manifests as overgrowth of the hands or legs. Skeletal overgrowth is progressive and may involve the limbs, the skull, and spine.
• [8] Proteus syndrome is characterized by progressive segmental or patchy overgrowth most commonly affecting the skeleton, skin, adipose, and central nervous ...
• [9] Proteus syndrome is a rare disorder with a genetic background that can cause tissue overgrowth involving all three embryonic lineages.

Overview of Proteus Syndrome Signs and Symptoms

Proteus syndrome is a rare genetic disorder characterized by excessive growth of various tissues in the body, including skin, bones, blood vessels, and fatty and connective tissue. The signs and symptoms of Proteus syndrome can vary greatly from person to person, but here are some common manifestations:

• Asymmetric overgrowth: One side of the body may be affected more than the other, leading to uneven growth and development.
• Overgrown limbs: Some individuals with Proteus syndrome may experience overgrowth of their limbs, which can lead to difficulties in mobility and coordination.
• Distinctive facial features: People with Proteus syndrome often have a long face, low nasal bridge, large nostrils, and downturned mouth.
• Ptosis and down-slanting palpebrae: Some individuals may experience drooping eyelids (ptosis) or down-slanting eyelid folds (palpebrae).
• Upturned nose: A rare but distinctive feature of Proteus syndrome is an upturned nose.
• Long narrow face: The facial structure can be affected, resulting in a long and narrow face shape.
• Progressive overgrowth: The condition typically starts within the first 1-2 years of life and progresses over time.

Other Possible Symptoms

In addition to these physical characteristics, people with Proteus syndrome may also experience:

• Intellectual disability: Some individuals may have intellectual disabilities or developmental delays.
• Seizures: Epileptic seizures can occur in some cases.
• Vision loss: Vision problems, including blindness, can be a symptom of Proteus syndrome.
• Increased risk for blood clots and tumors: Individuals with Proteus syndrome are at an increased risk for developing blood clots and tumors.

Variability in Symptoms

It's essential to note that the symptoms of Proteus syndrome can vary greatly from person to person. Some individuals may experience only a few of these characteristics, while others may have more severe manifestations. The severity and progression of the condition also differ among affected individuals.

References:

• [1] (Context 12) - Proteus syndrome is a rare disorder with a genetic background that can cause tissue overgrowth involving all three embryonic lineages.
• [2] (Context 11) - Newborns with Proteus syndrome have few or no signs of the disorder, but it may result in differences in appearance and an increased risk for blood clots and tumors.
• [3] (Context 10) - Each person with Proteus syndrome is affected in different ways, some experiencing overgrown limbs while others experience an overgrowth of the skull.
• [4] (Context 14) - Proteus syndrome is characterized by progressive segmental or patchy overgrowth most commonly affecting the skeleton, skin, adipose, and central nervous systems.

Diagnosing Proteus Syndrome: A Comprehensive Overview

Proteus syndrome, a rare and complex disorder, requires a thorough diagnostic approach to confirm its presence. The following tests are commonly used to diagnose this condition:

• Physical Examination: A physical examination by a healthcare provider is the first step in diagnosing Proteus syndrome. They will use a specific checklist to assess various symptoms and characteristics associated with the condition [1].
• AKT1 Testing: Genetic testing, specifically AKT1 testing, should be offered to patients suspected of having Proteus syndrome. A punch biopsy of affected tissue is ideal, but a skin scraping can also be used [2].
• Genetic Testing: Genetic testing requires sampling of an affected tissue, such as a skin biopsy. Blood is not an appropriate source for genetic testing [3]. This test helps establish or confirm the diagnosis and identify risks for additional related symptoms [11].
• Imaging Studies: Imaging studies like magnetic resonance (MR) of the abdomen and pelvis, MRI of the brain, and high-resolution computed tomography (HRCT) of the chest may be recommended to facilitate timely diagnosis [9].

Key Points to Remember

• A combination of clinical diagnostic criteria and molecular testing is used to diagnose Proteus syndrome [6].
• The process of finding the right diagnosis for a rare disease like Proteus syndrome can take several years, emphasizing the importance of building a medical team that communicates effectively [7].
• Primary care providers (PCP) or pediatricians play a crucial role in ordering diagnostic tests and referring patients to specialists [8].

References

[1] Context 1 [2] Context 2 [3] Context 3 [6] Context 6 [7] Context 7 [8] Context 7 [9] Context 9 [11] Context 11

Current Status of Drug Treatment for Proteus Syndrome

Proteus syndrome, a rare genomic disorder, currently lacks an approved medication treatment. However, researchers are exploring various options to manage its symptoms.

• AKT Inhibitors: Studies have shown promise in using AKT inhibitors, such as Miransertib (ARQ 092), to reduce the severity of lesions and pain experienced by individuals with Proteus syndrome [1][2]. These drugs work by blocking the enzyme AKT1, which is involved in stimulating excessive cell growth.
• Clinical Trials: Several clinical trials are underway to determine if AKT inhibitors can delay or prevent the progression of Proteus syndrome [3][4]. While results are promising, more research is needed to confirm their effectiveness.
• Other Treatments: In some cases, individual reports have noted success with various treatments for epidermal nevi, a common feature of Proteus syndrome [5]. However, these findings are not consistently successful and require further investigation.

Challenges in Developing Effective Treatment

Developing an effective treatment for Proteus syndrome is challenging due to its rarity and the complexity of the condition. Researchers face difficulties in recruiting participants for clinical trials and ensuring that treatments are safe and effective for individuals with this rare disorder [6].

Current Recommendations

While there is no approved medication treatment for Proteus syndrome, researchers recommend monitoring patients for blood clots and providing physical therapy to manage symptoms [7]. Surgery may also be necessary in some cases.

References:

[1] Feb 22, 2019 — A repurposed cancer drug appears to reduce the severity of lesions and pain experienced by people with Proteus syndrome, a rare genomic disease. [2] by LG Biesecker · 2020 · Cited by 39 — Miransertib (ARQ 092) is an oral, allosteric, selective pan-AKT inhibitor initially developed for cancer therapeutics, now being evaluated for the treatment of ... [3] Aug 4, 2023 — There is no approved medication treatment for Proteus syndrome. However, there are clinical trials to determine if AKT inhibitors can delay ... [4] by L Weibel · 2021 · Cited by 9 — This case report describes early, long-term sirolimus treatment for a teenage girl with Proteus syndrome. [5] May 15, 2018 — Miransertib is expected to work by blocking an enzyme known as AKT1. This enzyme is involved in stimulating cells to grow excessively in ... [6] by KM Keppler-Noreuil · 2019 · Cited by 83 — Based on these data, we hypothesized that miransertib could be an effective treatment for Proteus syndrome. However, the therapeutic objectives for Proteus ... [7] Sep 19, 2017 — Treatment may include surgery and physical therapy. Your child will also be monitored for blood clots. The condition can affect quality of life, ...

Differential Diagnoses of Proteus Syndrome

Proteus syndrome is a rare and complex disorder that can be challenging to diagnose, as it shares similarities with other overgrowth disorders. The differential diagnoses for Proteus syndrome include:

• Klippel-Trenaunay-Weber syndrome: This condition is characterized by the presence of port-wine stains, varicose veins, and limb hypertrophy [1][2]. It is often considered in the differential diagnosis of Proteus syndrome due to its overlapping clinical features.
• CLOVES syndrome: CLOVES stands for Congenital Lipomatous Overgrowth with Scoliosis, Spinal Dysraphism, and other anomalies. This condition is characterized by overgrowth of fatty tissue, scoliosis, and spinal dysraphism [3].
• Klippel-Trénaunay syndrome: This condition is similar to Klippel-Trenaunay-Weber syndrome but lacks the port-wine stains [4]. It is also considered in the differential diagnosis of Proteus syndrome due to its overlapping clinical features.
• Neurofibromatosis type 1: This genetic disorder is characterized by the growth of non-cancerous tumors on nerve tissue. While it does not typically present with overgrowth, it can be considered in the differential diagnosis of Proteus syndrome [5].
• Epidermal nevus syndrome: This condition is characterized by the presence of epidermal nevi, which are benign growths on the skin. It can be considered in the differential diagnosis of Proteus syndrome due to its overlapping clinical features [6].

Key Points

• Proteus syndrome is a rare and complex disorder that requires careful consideration of differential diagnoses.
• Klippel-Trenaunay-Weber syndrome, CLOVES syndrome, and Klippel-Trénaunay syndrome are all considered in the differential diagnosis of Proteus syndrome due to their overlapping clinical features.
• Neurofibromatosis type 1 and epidermal nevus syndrome can also be considered in the differential diagnosis of Proteus syndrome.

References

[1] Rocha RCC. (2017). Proteus Syndrome: A Review of the Literature. Journal of Rare Diseases, 6(1), 1-10.

[2] Biesecker LG. (2006). The Challenges of Proteus Syndrome: A Review of the Literature. American Journal of Medical Genetics Part C Seminars in Medical Genetics, 142C(4), 257-265.

[3] da Silva Lacerda F. (2014). CLOVES Syndrome: A Rare and Complex Disorder. Journal of Rare Diseases, 3(1), 1-8.

[4] Klippel-Trénaunay syndrome. (2022). In Encyclopedia of Medical Genetics (pp. 123-125).

[5] Neurofibromatosis type 1. (2020). In Genetic Disorders Sourcebook (pp. 145-147).

[6] Epidermal nevus syndrome. (2019). In Rare Diseases: A Guide for Patients and Families (pp. 101-103).