Understanding Two Rare Vascular Genetic Conditions: What Patients Need to Know
Hereditary hemorrhagic telangiectasia (HHT) causes abnormal, fragile blood vessels that lead to bleeding, while Peutz-Jeghers syndrome (PJS) is marked by intestinal polyps and dark skin spots. Both are genetic, but HHT affects blood vessels, and PJS increases cancer risk.
Genetic disorders affecting the vascular system can significantly impact quality of life, yet many remain poorly understood even among healthcare professionals.
Hereditary Hemorrhagic Telangiectasia (HHT) and Peutz-Jeghers Syndrome (PJS) represent two such conditions that, while sharing some superficial similarities, are fundamentally different in their presentation, complications, and management strategies.
At Vein Center Doctor, our specialists are committed to helping patients understand these rare conditions and providing appropriate care for related vascular manifestations.
Whether you’re a patient recently diagnosed with one of these conditions, a family member seeking information, or someone experiencing concerning symptoms, this article aims to provide clarity on these often-confused disorders.
If you or a loved one is experiencing frequent nosebleeds or visible telangiectasias, contact the Vein Center Doctor today for expert evaluation and personalized care.
Living with unwanted veins is a thing of the past, when you can simply schedule a free consultation with Vein Center Doctor and find your ideal solution today.
What is Hereditary Hemorrhagic Telangiectasia (HHT)?
Hereditary Hemorrhagic Telangiectasia, also known as Osler-Weber-Rendu Syndrome, is a rare genetic disorder that affects approximately 1 in 5,000 to 8,000 people worldwide. HHT primarily impacts the blood vessels, causing them to develop abnormally throughout the body.
The Vascular Abnormalities of HHT
The hallmark of HHT is the development of telangiectasias and arteriovenous malformations (AVMs):
- Telangiectasias are small dilated blood vessels near the surface of the skin or mucous membranes. They appear as red or purplish spots that blanch (temporarily lose color) when pressed. These fragile vessels can rupture easily, leading to bleeding.
- Arteriovenous Malformations (AVMs) are abnormal connections between arteries and veins that bypass the capillary system. Normally, blood flows from arteries to capillaries to veins, but AVMs create a direct connection between the arterial and venous systems. These can develop in various organs, including the lungs, brain, liver, and digestive tract.
Common Symptoms and Manifestations of HHT
HHT presents with a constellation of symptoms, with bleeding being the most prominent:
1. Recurrent Epistaxis (Nosebleeds)
Nosebleeds are often the earliest and most common manifestation of HHT, affecting over 90% of patients by adulthood. These nosebleeds:
- Typically begin before age 20
- Can be frequent (daily in some cases)
- Range from mild to severe (requiring transfusion in extreme cases)
- Often occur spontaneously without trauma
- Can significantly impact quality of life
2. Visible Telangiectasias
Telangiectasias commonly appear on:
- Lips
- Tongue
- Face (especially the cheeks)
- Fingertips
- Inside the mouth (buccal mucosa)
- Conjunctiva of the eyes
These visible manifestations typically develop during adolescence or early adulthood and increase in number with age.
3. Gastrointestinal Bleeding
Approximately 25-30% of HHT patients experience gastrointestinal bleeding, which:
- Usually begins after age 50
- Can be chronic and insidious
- Often leads to iron-deficiency anemia
- May cause fatigue, weakness, and shortness of breath
- Can be life-threatening in severe cases
4. Symptoms Related to Internal AVMs
Depending on their location, AVMs can cause various symptoms:
- Pulmonary AVMs (affecting 15-50% of patients)
- Shortness of breath or decreased exercise tolerance
- Hemoptysis (coughing up blood)
- Hypoxemia (low blood oxygen levels)
- Paradoxical emboli leading to stroke or brain abscess
- Cerebral AVMs (affecting 10-20% of patients)
- Headaches
- Seizures
- Neurological deficits
- Intracranial hemorrhage
- Hepatic AVMs (affecting 30-70% of patients)
- Often asymptomatic
- Can lead to high-output heart failure
- Portal hypertension
- Biliary disease
Genetic Basis of HHT
HHT follows an autosomal dominant inheritance pattern, meaning that a person needs only one copy of the mutated gene to develop the condition. A child of an affected parent has a 50% chance of inheriting the disorder.
Several genes have been identified in HHT:
- ENG gene (on chromosome 9) – associated with HHT type 1
- ACVRL1 gene (on chromosome 12) – associated with HHT type 2
- SMAD4 gene – causes a combined syndrome of HHT and juvenile polyposis
These genes are all involved in the TGF-beta signaling pathway, which is crucial for blood vessel development and maintenance.
Discover your genetic risk for HHT—book a genetic counseling session with Vein Center Doctor today to take control of your health.
What is Peutz-Jeghers Syndrome (PJS)?
Peutz-Jeghers Syndrome is a rare genetic disorder characterized by the development of distinctive mucocutaneous pigmentation and hamartomatous polyps throughout the gastrointestinal tract. It affects approximately 1 in 25,000 to 280,000 people worldwide.
Characteristic Features of PJS
PJS has two primary manifestations:
1. Mucocutaneous Pigmentation
The distinctive pigmented macules of PJS:
- Appear as flat, blue to dark brown spots
- Range from 1-5 mm in diameter
- Most commonly occur around the lips, inside the mouth, on the hands, feet, and genital region
- Often develop in early childhood (sometimes present at birth)
- May fade during puberty and adulthood, especially from the lips
2. Hamartomatous Polyps
These distinctive polyps:
- Are benign overgrowths of normal tissue
- Contain well-organized smooth muscle arranged in a characteristic branching pattern
- Primarily affect the small intestine (jejunum and ileum), but can occur throughout the entire gastrointestinal tract
- Usually develop by adolescence
- Can vary in size from a few millimeters to several centimeters
- Can be single or multiple (usually multiple)
Common Symptoms and Manifestations of PJS
PJS presents with various symptoms, primarily related to the polyps in the gastrointestinal tract:
1. Gastrointestinal Symptoms
- Abdominal Pain: Often crampy and intermittent
- Intussusception: The telescoping of one segment of intestine into another, causing obstruction
- Gastrointestinal Bleeding: Usually chronic and occult (hidden), sometimes acute
- Small Bowel Obstruction: Due to large polyps or intussusception
- Iron Deficiency Anemia: Secondary to chronic blood loss
2. Pigmentation-Related Features
- Cosmetic Concerns: Particularly regarding perioral (around the mouth) pigmentation
- Generally asymptomatic physically
3. Cancer-Related Symptoms
Individuals with PJS have a significantly increased risk of developing various cancers, including:
- Colorectal, gastric, and pancreatic cancers
- Breast and ovarian cancers in females
- Sex cord tumors with annular tubules or adenoma malignum of the cervix in females
- Sertoli cell tumors of the testes in males
These cancers can present with symptoms specific to the affected organ systems.
Genetic Basis of PJS
PJS is caused by mutations in the STK11 gene (also known as LKB1), located on chromosome 19p13.3. Like many genetic disorders, PJS follows an autosomal dominant inheritance pattern, meaning a child of an affected parent has a 50% chance of inheriting the condition.
The STK11 gene encodes a tumor suppressor protein that helps regulate cell growth and division. Mutations in this gene disrupt this regulation, leading to the development of hamartomatous polyps and increasing cancer risk.
Key Differences Between HHT and PJS
While both HHT and PJS are rare genetic disorders with some overlapping features, they have distinct characteristics that differentiate them from one another:
1. Primary Manifestations
| HHT | PJS |
| Telangiectasias and arteriovenous malformations (AVMs) | Mucocutaneous pigmentation and hamartomatous polyps |
| Primarily a vascular disorder | Primarily a polyposis syndrome with pigmentation |
| Results in fragile blood vessels prone to rupture and bleeding | Results in polyp formation with potential for obstruction and malignant transformation |
2. Visible Physical Signs
| HHT | PJS |
| Red or purple telangiectasias on skin and mucous membranes | Blue to dark brown pigmented macules (freckle-like spots) |
| Lesions represent dilated blood vessels | Lesions represent melanin deposition in the skin |
| Common on lips, tongue, face, fingertips | Common around lips, inside mouth, hands, feet |
| Increase in number with age | Often appear in childhood, may fade with age |
3. Gastrointestinal Involvement
| HHT | PJS |
| Telangiectasias in GI tract mucosa | Hamartomatous polyps throughout GI tract |
| Bleeding is the primary concern | Polyp-related complications (intussusception, obstruction) and bleeding are concerns |
| No significant polyp formation | Multiple polyps, predominantly in small intestine |
| GI bleeding typically begins after age 50 | GI symptoms can begin in childhood or adolescence |
4. Major Complications
| HHT | PJS |
| Epistaxis (nosebleeds), often severe and recurrent | Intestinal intussusception and obstruction |
| Iron deficiency anemia from chronic bleeding | Iron deficiency anemia from polyp-related bleeding |
| Stroke, brain abscess (from pulmonary AVMs) | Significantly increased cancer risk in multiple organs |
| Organ dysfunction from large AVMs | Generally no organ dysfunction unless cancer develops |
5. Cancer Risk
| HHT | PJS |
| Generally not associated with significantly increased cancer risk | Substantially increased risk for multiple cancers |
| Some evidence of slightly increased risk of certain cancers | Lifetime cancer risk up to 85% |
| Main health risks are from bleeding and vascular complications | Cancer surveillance is a major component of management |
Diagnosis: How to Identify HHT vs. PJS
Diagnosing HHT
The diagnosis of HHT is typically based on the Curaçao criteria, which include:
- Epistaxis: Spontaneous, recurrent nosebleeds
- Telangiectasias: Multiple, at characteristic sites (lips, oral cavity, fingers, nose)
- Visceral Lesions: Such as gastrointestinal telangiectasias, pulmonary, hepatic, cerebral, or spinal AVMs
- Family History: A first-degree relative with HHT according to these criteria
The diagnosis is:
- Definite: If three or four criteria are present
- Possible or suspected: If two criteria are present
- Unlikely: If fewer than two criteria are present
Genetic testing can confirm the diagnosis by identifying mutations in the ENG, ACVRL1, SMAD4, or GDF2 genes.
Diagnosing PJS
The diagnosis of PJS is typically based on clinical criteria that include:
- Characteristic Mucocutaneous Pigmentation: Especially around the lips and mouth
- Hamartomatous Polyps: In the small intestine, confirmed by histopathology
- Family History: Of PJS
For a definitive diagnosis, at least two of the following are required:
- Two or more histologically confirmed PJS-type hamartomatous polyps
- Characteristic mucocutaneous pigmentation in the patient
- Family history of PJS
Genetic testing for mutations in the STK11 gene can confirm the diagnosis.
Get an accurate diagnosis for HHT or PJS with the trusted expertise of Vein Center Doctor—schedule your evaluation now.
The Role of Vein Specialists in Managing HHT
At Vein Center Doctor, our specialists play a crucial role in the multidisciplinary management of patients with HHT, particularly in addressing the vascular manifestations of the condition:
1. Diagnosis and Assessment
- Identification of cutaneous and mucosal telangiectasias
- Evaluation of vascular malformations
- Assessment of bleeding severity and impact
2. Treatment Options
- Sclerotherapy: An effective treatment for smaller telangiectasias and spider veins where a sclerosing agent is injected directly into the affected vessels, causing them to collapse and gradually fade
- VenaSeal: A cutting-edge adhesive closure system that safely and effectively treats varicose veins by sealing affected vessels with a medical-grade adhesive, offering a comfortable alternative with minimal downtime
- Radiofrequency Ablation (RFA): A minimally invasive procedure that uses heat to close problematic varicose veins and redirect blood flow to healthier vessels, particularly beneficial for patients with recurrent bleeding from larger vascular malformations
- Venous Compression Therapy: The strategic use of compression garments to improve circulation, reduce swelling, and help manage symptoms in patients with vascular abnormalities
3. Collaborative Care
- Coordination with other specialists (ENT, gastroenterology, interventional radiology)
- Referral for genetic testing and counseling
- Family screening recommendations
4. Ongoing Management
- Regular follow-up to monitor progression
- Adjustment of treatment plans as needed
- Education about self-care and prevention of complications
Conclusion
While Hereditary Hemorrhagic Telangiectasia and Peutz-Jeghers Syndrome might initially appear similar due to their genetic inheritance patterns and potential for gastrointestinal bleeding, they represent fundamentally different disorders.
Understanding these differences is crucial for proper diagnosis, management, and long-term care planning. Both conditions require a multidisciplinary approach, regular surveillance, and specialized interventions to minimize complications and improve quality of life.
If you or a family member is experiencing symptoms suggestive of either condition, seeking evaluation from specialists familiar with these rare disorders is essential. At Vein Center Doctor, our team of specialists is experienced in diagnosing and managing vascular abnormalities, including those associated with HHT, and can provide appropriate referrals for comprehensive care.
For more information about our services or to schedule a consultation regarding vascular conditions, please contact the Vein Center Doctor today.
Dr. Sood at Vein Center Doctor is always happy to offer free consultations to anyone looking to understand their vein issues. Don’t spend another day wondering how to make those visible veins go away. Call us at 862-227-1143 today!
