Neurovascular phenotypes in hereditary haemorrhagic telangiectasia patients according to age. Review of 50 consecutive patients aged 1 day-60 years

Hereditary haemorrhagic telangiectasia (HHT) is inherited as an autosomal dominant trait with varying penetrance and expressivity. Some of the most devastating consequences of this disease result from cerebral vascular malformations that manifest themselves in either arteriovenous fistulae (AVF), small nidus-type arteriovenous malformations (AVM) or micro-AVMs with a nidus less than 1 cm in size. The purpose of this study was to compare the phenotypes of CNS-manifestations of HHT with the age of the patient. The charts and angiographic films of 50 patients diagnosed with HHT according to the Curacao criteria were retrospectively evaluated concerning age of onset of symptoms, or, if not applicable of first consultation. The files were reviewed for clinical presentation, family and personal history, while the patients' angiograms were analysed with respect to the number of lesions (single and multiple), the location (superficial supratentorial, deep supratentorial, infratentorial, and spinal), and type of lesion (fistulous AVM, nidus-type AVM, and micro-AVM). A total of 75 central nervous system manifestations of HHT were found. Lesions included seven spinal cord AVFs that were all present in the paediatric age group (mean age: 2.2 years), 34 cerebral AV fistulae, all but two affected patients were less than 6 years (mean age 3.0). Sixteen nidus type AVMs (mean age: 23.1 years) and 18 micro-AVMs (mean age: 31.8 years) were found. HHT displays an age-related penetrance of clinical manifestations. Since members of the same family can present with completely different phenotypes of this disease there seems to be no relationship between the type of mutation and the phenotype of the disease. Since there seems to be a continuum of vascular abnormalities (from large fistulous areas to small AVMs and micro-AVMs) associated with HHT, the most likely determinating factor of the HHT phenotype is the timing of the revealing event in relation to the maturity of the vessel. Presumably, the trigger of the quiescent genetical abnormality transforms a ''dormant'' disease into a morphologically and therefore clinically detectable one by impairing a specific vessel segment at a specific (more or less vulnerable) period of time. The nature of this triggering event is, however, as of yet unclear. (orig.)