Screening and diagnosis
Relatives of an HHT patient should be screened once; women especially before they become pregnant. Screening of family members, adults as well as children, is strongly advised for three reasons:
- The diagnosis is easily missed by other doctors, because HHT is relatively unknown and because experience is necessary to provide a proper diagnosis. Quite often relatives, who think they do not have HHT, prove to have HHT. And on the other hand, family members, who think they have HHT because of nose bleeds or red dots, sometimes do not have HHT.
- Patients with HHT often have dangerous vascular abnormalities in the lungs and/or the brains without knowing it. These AVMs may cause sudden and serious complications that can be prevented, because the AVMs can be treated effectively.
- Screening is important for future offspring. A child will not be affected by the disease if the parent is not affected, because a generation is never skipped. If the parent is affected, 50% of their children are likely to have the disease.
The screening is performed to confirm or exclude the clinical diagnosis and, if requested, to confirm or exclude a genetic (DNA) diagnosis. A search for the presence of vascular abnormalities in the lung - and sometimes in the brain – will also be done. Examination of the liver is restricted to the testing of liver enzymes in the blood when indicated; these are elevated in case of significant AVM’s. The intestines are not usually examined.
Screening of adults and children
The screening of adults consists of:
- a medical history;
- general physical examination including cappilar microscopy of the finger cuticles;
- examination by the ENT specialist;
- a chest X-ray or (when indicated) CT scan;
- routine laboratory examination and
- the so-called echo bubble test. During the echo bubble test a mixture of physiological saline solution and the patient’s blood, containing tiny air bubbles, is injected into a vein in the arm. The air bubbles will pass through the lung if there is a vascular abnormality and can be visualised in the heart by the cardiologist using echography.
Blood for a DNA test is only taken with permission of the patient (or parent/guardian).
An MRI scan of the brain is only made when the diagnosis of HHT is definite and after giving the patient full information about the consequences.
The screening of children is less extensive and painful examinations such as punctures and taking blood are avoided so as not to frighten the child. There is often some uncertainty regarding the clinical diagnosis, because the typical abnormalities may not appear until later in life. The screening of children is particularly done to detect a pulmonary lesion in time.
The screening of children consists of:
- asking the parent about the child’s/family’s medical history;
- a general physical examination;
- microscopic examination of the cuticles (see symptoms of the skin) and of the nasal mucosa by the ear, nose and throat specialist;
- a chest-X-ray and
- measurement of the oxygen saturation using a cap over the fingertip (oximetry).
Examination of blood and DNA is only done in rare cases.
It is important to realize that the clinical diagnosis of HHT is easily missed in a child. A second and third examination is therefore required after puberty and at the age of 18 years, unless the diagnosis has been ruled out by a DNA test.
A genetic diagnosis (from looking at the person’s DNA) is possible in 95% of the Dutch HHT families.
The clinical diagnosis is made if three of the four "Curacao-criteria" are present. These criteria are:
- There is a first-degree family member with HHT (a parent, sibling or a child).
- Spontaneous, recurrent nose bleeds.
- Telangiectases on the typical sites. A doctor needs experience to recognise them and sometimes a microscope is required to detect them in the nose or nail fold.
- Vascular abnormalities in other organs such as lungs, brains, or liver. Detection requires a radiological or ultrasound examination.
The diagnosis remains questionable when only two criteria are present. This occurs particularly in children, because the vascular abnormalities develop during life. The diagnosis is also more difficult if there is a mutation of ALK-1 (HHT type 2), because this form of the disease has a milder course with few abnormalities in the lung or brain. A second examination when adulthood is reached is necessary if the diagnosis remains uncertain, unless a DNA test can exclude the disease.
DNA research in the Netherlands is advanced: the family mutation is known in 95% of the families. DNA research means that a search is done for the family mutation, usually in the blood. The disease is absent when the mutation is absent. The chance that a family member has another mutation than the family mutation is theoretically present, but extremely small. The disease is present when the mutation is seen, even if there are no symptoms at that time, for instance in a baby.
A DNA test yields definite results in over 95% of individuals.
The presence or absence of HHT can be demonstrated in 95% of the family members of a Dutch patient with HHT, because the causative mutation is known in 95% of Dutch families. However, it is necessary to determine to which family the patient belongs (family lineage or family tree). A new family with HHT also has a 95% chance that the mutation will be found. A DNA test is best done on relatively fresh blood that can be taken in a regular laboratory. It will take several weeks before the results are known.
DNA testing is especially important if HHT is not obviously present or absent in clinical terms. This is often the case in children. The parents have to give written consent for DNA testing of their children and they should realize that a definite, conclusive result follows. This can cause problems in a child that has no clinical symptoms, but is given a genetic diagnosis of HHT. A consultation with a clinical geneticist may be of help in taking decisions about DNA testing. It is also possible to ask for the booklet "Do I really want to know?" ("Wil ik het wel weten?") at the department of Medical Genetics of the UMC Utrecht (see organisations and addresses).
Genealogy (family lineage)
A mutation is usually specific for a particular family. In the Netherlands about 260 different families and over 232 different mutations are known. Some families have the same mutation. The department of Medical Genetics of the UMC Utrecht traces the lineage of these families in order to find out whether there is a common ancestor. So far, several “different” families appear to be related.
- To apply for screening, you can contact Mrs. Liesbeth Dekter at: T 088 320 15 48.
- For urgent questions you can contact our HHT nurses at T 088 320 15 47.
The screening takes place at our outpatient Clinic (polikliniek) for Pulmonary diseases, located at St. Antonius Hospital:
- Koekoekslaan 1, 3435 CM Nieuwegein, the Netherlands.
The hospital can be easily reached by public transport (there is a direct tramline from the central railway station in Utrecht) or by car.