Craniofacial and oral alterations in patients with Neurofibromatosis 1.

ABTSRACT: Neurofibromatosis type 1 (NF1) is one of the most common inherited syndromes. The literature on craniofacial alterations associated with NF1 has been limited and partially contradictory. This review is based on literature search and the results of the clinical study "Craniofacial and Oral Alterations and Speech in patients with Neurofibromatosis 1", carried out at the University of Turku and Turku University Hospital, Finland in 2006-2012. By the end of 2012, a total of 110 NF1 patients, 54 female and 56 male patients, were examined.A part of our results confirms pre-existing understanding, a part is contradictory to previous considerations based mainly on case reports, and some are entirely novel. Specifically, our results confirmed that enlargement the mandibular canal is the most common abnormality of the mandible in patients with NF1. It should be noted, however, that this finding does not require treatment. Caries was not a major problem. In fact, it was less frequent in NF1 patients compared to reference population. These findings abrogate some previous perceptions. Novel findings of our project include periapical cemental dysplasia in females; short jaws, a finding which usually does not affect bite; and immunohistological analysis of oral mucosal abnormalities. Pioneering study on speech showed that various deviations were very common: As many as 94% of the participants showed some alterations.To conclude, the awareness of craniofacial alterations common in NF1would help avoiding unnecessary and even harmful involvement, e.g. of periapical cemental dysplasia or enlarged mandibular canal which do not require treatment.

Deciduous neonatal line: Width is associated with duration of delivery.

The delivery-related neonatal line (NNL) appears into the enamel of primary teeth and first permanent molars at birth and is a marker of live birth process. It varies in width and its location, is different in each deciduous tooth type, and is indicative of gestation time. It is unclear which triggers determine NNL at birth. Our objective was to investigate the effect of the duration and mode of delivery on NNL width. NNL of 129 teeth, a collection derived from a long-term, prospectively followed population cohort, was measured under light microscope. Altogether, 54 sections with most optimal plane of sectioning were analysed for the duration and mode of delivery. NNL was detected in 98% of the deciduous teeth with the median width of 9.63µm (min 3.16µm, max 27.58µm). A prolonged duration of vaginal delivery was highly significantly associated with a narrower NNL (r=-0.41, p=0.0097). No significant association was found between the width of NNL and mode of delivery (p=0.36). NNL is demonstrable in virtually all deciduous teeth. The width seems to be inversely proportional to the duration of delivery. Causes of the inverse proportion are speculated to result from altered amelogenesis induced by prolonged and intensified delivery-associated stress. Further research is needed to clarify the underlying mechanisms.

Dental age in patients with neurofibromatosis 1.

Neurofibromatosis type 1 (NF1) is a common, hereditary, neurocutaneous skeletal condition with a variety of osseous manifestations. Although NF1 also affects craniofacial structures, the literature has only limited information related to the effect of NF1 on dental development. In this study the dental age of 34 Finnish NF1 patients, 8-17 yr of age, was estimated using the Demirjian & Goldstein method. The dental age of children with NF1 was similar to that of a Finnish control population. The findings suggest that NF1 does not affect the timing of tooth development.

Oral soft tissue alterations in patients with neurofibromatosis.

Our aim was to characterize the type and frequency of oral soft tissue alterations in neurofibromatosis. A total of 103 patients with neurofibromatosis 1 (NF1) and three patients with neurofibromatosis 2 (NF2) were clinically evaluated for their oral soft tissue alterations. Disturbing growths were removed from nine patients with NF1 and from one patient with NF2. The specimens were analyzed using routine histological methods and with immunohistochemistry using antibodies to S100, type IV collagen, CD34, neurofilament, and neuron-specific tubulin (TUBB3). Alterations including oral tumors, overgrowths of gingival soft tissue, and enlarged papillae of the tongue were discovered in 74% of NF1 patients. The results showed that three tumors clinically classified as plexiform neurofibromas and five out of six discrete mucosal tumors displayed histology and immunohistology consistent with that of neurofibroma. The histology of one palatal lesion resembled that of a scar, and the lesion removed from the patient with NF2 was classified as an amyloid tumor. To conclude, oral soft tissue growths are common findings in NF1, but most lesions do not require treatment and the patients may even not be aware of these alterations. Collagen IV, S100, and CD34 are useful biomarkers in the analysis of NF1-related oral soft tissue tumors. The clinicians should recognize that oral soft tissue alterations are relatively common in NF1. Some of the growths are disturbing, and plexiform neurofibromas may bear a risk of malignant transformation.

Radiographic findings in the jaws of patients with neurofibromatosis 1.

PURPOSE: Neurofibromatosis 1 (NF1) is a neurocutaneous-skeletal disorder with variable phenotypic expression and an incidence of 1:3,000 worldwide. The objective was to characterize the NF1-related radiologic alterations found in the jaws of these patients. PATIENTS AND METHODS: In total, 102 patients with NF1 were included in the present study. Six patients had a plexiform neurofibroma in the craniofacial region. RESULTS: Radiologic abnormalities in the jaws were found in 29 of 102 patients with NF1, including 6 patients with plexiform neurofibroma in the head and neck region. The most common radiologic finding was enlargement of the mandibular canal. The most prominent skeletal deformities and alterations of varying severity were detected in the jaws of 6 patients with plexiform neurofibroma. In these patients, the skeletal deformities were seen on the side affected by the tumor and possibly caused by the tumor. In 1 patient, however, the skeletal changes were on the opposite side. CONCLUSIONS: Radiologic abnormalities were found in 29 of 102 patients. The most significant findings were profound deformities of the mandible and maxilla in all 6 patients with plexiform neurofibroma, but not in the other patients. The facial bone deformities found in young patients did not progress markedly at older ages with cessation of the patients' growth.

Short mandible, maxilla and cranial base are common in patients with neurofibromatosis 1.

Neurofibromatosis type 1 (NF1) is an autosomal-dominant neuro-cutaneous-skeletal syndrome. Neurofibromatosis type 1 is one of the Rasopathies, and at the cellular level NF1 results in a hyperactive Ras pathway. In the current investigation, our aim was to study lateral skull X-rays (cephalograms) to assess NF1-related craniofacial morphology. A total of 85 Finnish patients with NF1, including four patients with plexiform neurofibroma of the 5th cranial nerve, and their age- and gender-matched controls, were enrolled in the study. The results showed that patients with NF1 typically had a short mandible, maxilla, and cranial base compared with healthy controls, irrespective of age, but the results were statistically significant only in adults. The length of the mandible, the maxilla and the cranial base correlated with the height of patients under 19 yr of age, but this correlation was absent in adult patients. Thus, a tall adult patient with NF1 may have short jaws and a short cranial base. In conclusion, the NF1 gene apparently influences the growth of craniofacial bones, thus contributing to the craniofacial morphology in NF1.

Neurofibromatosis 1 and dental caries.

A total of 110 patients with neurofibromatosis 1 (NF1) were evaluated for their dental health. Appropriate cohorts from national Finnish databases were used as reference. The results showed that NF1 patients presented lower rate of caries compared to controls in age groups under 35 years. The differences between NF1 patients and the reference population diminished by age. In conclusion, (1) NF1 per se does not predispose to caries; and (2) even if NF1 had an adverse effect on dental health, poor outcome can be counteracted with good personal dental care supported by well organized primary health care. The results of the present study are important to report since a common anecdotal perception is that the rate of caries may be higher in NF1 compared to reference population.

Speech characteristics in neurofibromatosis type 1.

Neurofibromatosis 1 (NF1) is a neurocutaneous-skeletal disorder often accompanied with varying degrees of cognitive and motor problems that potentially affect speech and language. While previous studies have shown that NF1 may be associated with a variety of deviations in the patients' speech, they have not investigated the characteristics in phonetic detail. Our clinical observation that many patients share a distinct voice and manner of speaking led to the primary aim of this study, which was to present a comprehensive description of speech in NF1. A total of 62 patients with NF1 (age range 7-66 years), and a control group of 24 speakers (age range 7-62 years) were evaluated for their speech. The test sessions were recorded and the data were analyzed both by ear and by acoustic measurements. The data were analyzed separately by two trained phoneticians, and a summary was produced after comparing the two independent analyses. Various speech problems were observed among patients with NF1. Individual variation was remarkable, but the deviations were more common and severe in children than in adult patients. In addition, men with NF1 had more speech deviations than women with NF1. Findings include deviations in voice quality, problems in regulating pitch, deviant nasality, misarticulation, and disfluency. We suggest that difficulties in speech, particularly in regulating pitch, may have negative social implications. Our results highlight which components of speech require particular attention in speech therapy for patients with NF1.

Periapical cemental dysplasia is common in women with NF1.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a genetic disorder with skeletal involvement. Periapical cemental dysplasia is a rare finding in the normal population. METHOD: A total of 55 patients with NF1, 29 female and 26 male patients, were evaluated with orthopantomograms, supplemented with periapical radiographs if necessary. The vitality of the teeth was measured by two different testing methods. RESULTS: A novel finding was the occurrence of cemental dysplasia affecting the periapical area of vital mandibular teeth in 8 adult women with NF1. Thus, cemental dysplasia was detected in 34.8% of the adult female NF1 patients, while cemental dysplasia was not present in men or children with NF1. CONCLUSION: Periradicular cemental dysplasia is indeed a new NF1 related bone lesion type. Our finding suggests that this is the first reported sexual dimorphism in the manifestations of NF1. Cemental dysplasia of NF1 patients should not be confused with periapical findings caused by endodontic pathoses. The former do not require active therapy whereas in the latter root canal treatment is necessary.