Authors reply: New clues on the path of understanding unilateral naevoid telangiectasia

Editor We thank Daniele Torchia for his kind evaluation of our article, ‘Unilateral nevoid telangiectasia accompanied by neurological disorders’. We would like to address the comments. Daniele Torchia remarks is that unilateral nevoid telangiectasia (UNT) lesions are distributed in a segmental fashion, which is typical of the block-like (checkerboard) pattern of cutaneous mosaicism. He implies that UNT is actually a naevus (e.g. naevus flammeus and cutis marmorata telengiectatica congenita) or a mosaic manifestation of a disease. In this context, it is well known that some vascular symptoms, especially unilateral signs, are considerable from the standpoint of the neurological involvement. In our case series study, some neurological disorders are accompanied by UNT. Both dermal and neurological involvements are considered; there would be cooperative defect on the neurocutaneous developmental stages during the embryologic life. The onset of the skin signs or neurological disorders would be late during the adult life. Whether our findings are UNT-related or a coincidental observation is difficult to ascertain. However, we noticed that UNT lesions of the presented cases follow dermatomes or Blaschko’s lines. It might indicate the underlying neurological involvement. Because of the association of UNT with ipsilateral central and ⁄ or peripheral nervous system disturbances in our case series, Daniele Torchia thought that UNT might be a true syndrome (not to be confused with previous reports improperly labelling ‘UNT’ as ‘UNT syndrome’) in parallel with other telangiectatic naevi, which can be very well associated with internal malformations (e.g. Sturge-Weber sydrome, Klippel-Trenaunay syndrome, van Lohuizen syndrome etc.). So far, the aetiopathogenesis of UNT is not fully known. The lesions may be congenital or acquired. Hepatitis C, alcoholic cirrhosis, pregnancy, puberty and oral contraceptive drug use are reported among suspecting aetiological factors. There would be increased sensitivity of target organs or tissues towards hormonal agents as in hyperestrogenism or hyperthyroidism. Some authors reported that patients with UNT had no demonstrable underlying disease, condition or oestrogen receptor abnormality. Paradominant inheritance, in which an autosomal mutation results in loss of heterozygosity and gives rise to a mosaic patch or twin spots, may explain the rare occurrence of telangiectatic nevi in several family members. It was also suggested that the disorder would be developed by the increased levels of oestrogen because of the chromosomal mosaicism on the Blascho’s lines location. Daniele Torchia hypothesizes that UNT represents a mosaic manifestation of hereditary haemorrhagic telangiectasia (HHT, Osler-Rendu-Weber syndrome, OMIM #187300). The author specifies similarities in two disorders such as gastrointestinal involvement and neurological disturbances. Therefore, he recommends that UNT cases be tested for gene alterations, which have been shown to cause HHT. To understand this hypothesis, we offer to remember somatic mosaicism in patterned distribution of skin lesions in UNT and HHT. A number of diseases that usually involve the entire surface of the body can more rarely manifest with a patterned distribution. The generalized and patterned forms of the disease share the very same histology as well as a common aetiology in those cases, such as Zosteriform Darier and Darier disease (OMIM 124200) and the segmental and generalized forms of neurofibromatosis (OMIM 162200). In all of these cases, the generalized form of the disease is inherited in an autosomal-dominant fashion. The patterned form of the disorder is the expression of a particular type of mutation that is acquired after fertilization and the formation of the zygote and is known as a somatic mutation, in contrast with a germline mutation that is acquired before gamete fertilization. Any disorders during embriyogenesis or any genetic predispositions may cause UNT and neurological involvement in these patients. Genome analysis and neurological investigation will give us the opportunity to understand the real factors for development of UNT.