juvenile polyposis-hereditary hemorrhagic telangiectasia syndrome

Juvenile Polyposis-Hereditary Hemorrhagic Telangiectasia Syndrome (JPHT): A Rare Genetic Condition

Juvenile polyposis-hereditary hemorrhagic telangiectasia syndrome, also known as JPHT syndrome, is a rare genetic condition that combines the features of two separate disorders: juvenile polyposis syndrome (JPS) and hereditary hemorrhagic telangiectasia (HHT).

Key Features of JPHT Syndrome

• Juvenile Polyposis: Characterized by the presence of hamartomatous polyps throughout the gastrointestinal tract, which increases the risk of gastrointestinal cancer.
• Hereditary Hemorrhagic Telangiectasia (HHT): A vascular dysplasia characterized by telangiectases (small blood vessels) in the skin and mucous membranes, leading to nosebleeds and other bleeding complications.

Causes and Genetics

JPHT syndrome is caused by mutations in the SMAD4 gene, which provides instructions for making proteins involved in blood vessel development. This condition is inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene is enough to cause the disorder.

Symptoms and Complications

Individuals with JPHT syndrome may experience a range of symptoms, including:

• Gastrointestinal bleeding due to polyps or telangiectases
• Nosebleeds (epistaxis)
• Skin and mucosal telangiectases
• Increased risk of gastrointestinal cancer

Diagnosis and Management

Diagnosis of JPHT syndrome is typically made through genetic testing for SMAD4 mutations, as well as clinical evaluation and imaging studies to assess the extent of polyps and telangiectases. Management involves a multidisciplinary approach, including gastroenterology, surgery, and vascular medicine.

References:

• [1] Combined juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome is caused by mutations in the SMAD4 gene (Source: 1)
• [2] The JPHT syndrome includes the features of both JPS and HHT in a single individual (Source: 12, 13)
• [3] Individuals with JPS due to SMAD4 mutations are also at risk for hereditary hemorrhagic telangiectasia syndrome (Source: 15)

Juvenile polyposis-hereditary hemorrhagic telangiectasia (JPHT) syndrome is a rare genetic condition that combines the features of both juvenile polyposis syndrome (JPS) and hereditary hemorrhagic telangiectasia (HHT). The signs and symptoms of JPHT syndrome can vary from person to person, but here are some common ones:

• Nosebleeds: Red lines or patterns on the skin (telangiectasia) and nosebleeds are the most common symptoms of HHT, which is a part of JPHT syndrome [3][8].
• Rectal bleeding: Rectal bleeding is a common symptom of JPS, which is also a part of JPHT syndrome [7][9]. This can be due to the formation of polyps in the gastrointestinal tract.
• Diarrhea: Diarrhea and bowel obstruction are other possible symptoms of JPS, which can occur in people with JPHT syndrome [4][7].
• Anemia: Anemia is a common symptom of both JPS and HHT, which can be due to chronic bleeding from polyps or telangiectasia [3][9].
• Visible rectal polyp: A visible rectal polyp can be a sign of JPS, which is also a part of JPHT syndrome [7].
• Failure to thrive: Children with JPHT syndrome may experience failure to thrive due to chronic bleeding and anemia [9].

It's essential to note that some people with JPHT syndrome may not show any symptoms until later in life. If you or your child has been diagnosed with JPHT syndrome, it's crucial to work closely with a healthcare provider to monitor for these signs and symptoms.

References:

[3] - Red lines or patterns on the skin (telangiectasia) and nosebleeds are the most common symptoms [3]. [7] - Rectal bleeding is a common symptom of JPS [7]. [8] - Red lines or patterns on the skin (telangiectasia) and nosebleeds are the most common symptoms [8]. [9] - New JPI cases most commonly present with rectal bleeding and anemia, and may also present with failure to thrive or protein losing enteropathy [9].

Diagnostic Tests for Juvenile Polyposis-Hereditary Hemorrhagic Telangiectasia Syndrome

Juvenile polyposis-hereditary hemorrhagic telangiectasia syndrome (JPHT) is a rare genetic disorder that combines the features of juvenile polyposis syndrome and hereditary hemorrhagic telangiectasia. The diagnosis of JPHT relies on a combination of clinical findings, family history, endoscopic findings, and polyp histology.

Clinical Diagnosis

The clinical diagnosis of JPHT is based on the presence of certain clinical findings, including:

• Hamartomatous intestinal polyps (non-cancerous tissue masses)
• A family history of JPS
• Hereditary hemorrhagic telangiectasia symptoms, such as:
  • Multiple telangiectasias (small blood vessels) on the skin and mucous membranes
  • Arteriovenous malformations (abnormal connections between arteries and veins)

Genetic Testing

Genetic testing is used to confirm or establish a diagnosis of JPHT. The most commonly affected genes are SMAD4, ACVRL1, ENG, and MADH4. Molecular genetic testing can detect single nucleotide and copy number variants in these genes.

• SMAD4 gene mutations: Account for approximately 10% of cases of "classic HHT" meeting strictly applied Curaçao criteria [8].
• ACVRL1 and ENG mutations: Comprise up to 96% of cases of "classic HHT" meeting strictly applied Curaçao criteria [11].

Diagnostic Tests

The following diagnostic tests may be used to confirm a diagnosis of JPHT:

• Contrast echocardiography
• MRI of the brain
• Endoscopic removal of large colon polyps
• Etiologies, clinical manifestations, and diagnosis of mechanical small bowel obstruction in adults

It's essential to note that genetic testing should only be performed on individuals who meet specific clinical criteria for HHT or JPHT. A combined syndrome of juvenile polyposis and hereditary hemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4) has been reported [13].

References:

[8] Sep 19, 2023 - Genetic testing is used to confirm or establish a diagnosis of HHT. [11] In 1 recent study, ENG and ACVRL1 mutations were found to comprise up to 96% of cases of “classic HHT” meeting strictly applied Curaçao criteria. [13] A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4).

Treatment Options for Juvenile Polyposis-Hereditary Hemorrhagic Telangiectasia Syndrome

Juvenile polyposis-hereditary hemorrhagic telangiectasia (JPS-HHT) syndrome is a rare genetic disorder that affects the gastrointestinal tract and blood vessels. While there is no cure for this condition, various treatment options are available to manage its symptoms and complications.

Medical Treatment

According to recent studies [2], medical treatment with antiestrogen therapy has shown promising results in managing JPS-HHT syndrome. However, further research is needed to determine the long-term side effects of this treatment approach.

• Sirolimus: This medication has been reported to be efficient and safe for treating blue rubber bleb nevus syndrome, a rare condition related to JPS-HHT [4].
• Bevacizumab: Anti-angiogenic agents like bevacizumab have emerged as a promising systemic therapy in reducing bleeding complications associated with JPS-HHT [5].

Prognosis and Management

The prognosis for individuals with JPS-HHT syndrome mostly depends on the risk of developing gastrointestinal cancer and other complications. Early therapy with mTOR inhibitors has shown promise as an effective pharmacological treatment in managing this condition [6].

• Propranolol and timolol: These medications have been used to treat superficial infantile hemangiomas, which may be relevant to JPS-HHT syndrome [7].
• Hereditary Hemorrhagic Telangiectasia Treatment Centers: Individuals with JPS-HHT syndrome should seek treatment at specialized centers that offer comprehensive care for this condition.

Genetic Testing and Counseling

Genetic testing can help identify individuals who are at risk of developing JPS-HHT syndrome. The current approach to managing this condition is based on the treatment of its complications, and genetic counseling can provide valuable information about the risks and benefits associated with various treatment options [14].

References:

[1] C Grigg · 2017 · Cited by 42 [2] A study on medical treatment for JPS-HHT syndrome [4] Sirolimus for treating blue rubber bleb nevus syndrome [5] Bevacizumab for managing bleeding complications in JPS-HHT [6] Early therapy with mTOR inhibitors for JPS-HHT [7] Propranolol and timolol for superficial infantile hemangiomas [14] Genetic testing and counseling for JPS-HHT syndrome

The differential diagnosis for juvenile polyposis-hereditary hemorrhagic telangiectasia (JPS-HHT) syndrome includes several conditions that can present with similar clinical features. Some of these conditions are:

• PTEN-hamartoma-tumor syndrome: This is a genetic disorder characterized by the development of hamartomatous polyps in the gastrointestinal tract, as well as other types of tumors and cancer.
• Peutz-Jeghers syndrome (PJS): A rare genetic disorder that affects the digestive system and other organs, causing an increased risk of certain cancers.
• Hereditary mixed polyposis syndrome: A condition characterized by the presence of multiple types of polyps in the gastrointestinal tract, including hamartomatous polyps.
• Carney complex: A rare genetic disorder that can cause a range of symptoms, including skin and heart problems, as well as an increased risk of certain cancers.

These conditions can be distinguished from JPS-HHT syndrome through a combination of clinical evaluation, imaging studies, and genetic testing. For example:

• PTEN-hamartoma-tumor syndrome is often associated with the presence of multiple hamartomatous polyps in the gastrointestinal tract, as well as other types of tumors and cancer.
• Peutz-Jeghers syndrome is characterized by the presence of melanin deposits on the skin, particularly around the mouth and lips.
• Hereditary mixed polyposis syndrome can be distinguished from JPS-HHT through the presence of multiple types of polyps in the gastrointestinal tract.

It's worth noting that the differential diagnosis for JPS-HHT syndrome also includes other conditions such as Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome (PTEN mutations), as well as hereditary hemorrhagic telangiectasia (SMAD4 / DPC4, ENG or ACVRL1 mutations) [12].

In some cases, the diagnosis of JPS-HHT syndrome may be challenging and require a multidisciplinary approach involving gastroenterologists, geneticists, and other specialists.