Pigment International

: 2016  |  Volume : 3  |  Issue : 2  |  Page : 102--107

A clinical study of neurofibromatosis-1 at a tertiary health care centre in south India

Aarthi Lakshmanan, Aditya Kumar Bubna, Anandan Sankarasubramaniam, Mahalakshmi Veeraraghavan, Sudha Rangarajan, Murugan Sundaram 
 Department of Dermatology, Sri Ramachandra University, Chennai, Tamil Nadu, India

Correspondence Address:
Dr. Aditya Kumar Bubna
Assistant Professor, Department of Dermatology, Sri Ramachandra University, Porur, Chennai 600 116, Tamil Nadu


Background: Neurofibromatosis (NF)-1 is an autosomal dominant genodermatoses affecting numerous body systems. Though many associations are known, new findings encountered continue to intrigue the medical fraternity. Aim: A clinical study of various manifestations of NF-1. Methods: An observational study that was conducted on 30 patients with NF-1 over a period of 1 year. Results: Café-au-lait macules were identified in 28 (93.3%) patients. A family history of NF-1 was demonstrated in 10 (33.3%) patients. In 4 (13.3%) patients, plexiform neurofibromas were identified. Axillary freckling was seen in 27 (90%) patients and inguinal freckling in 17 (56.1%) patients. Lisch nodules were detected in 28 (93.3%) patients, conjunctival neurofibromas in 2 (6.7%) and conjunctival freckles in 3 (10%) patients. Bone changes were demonstrable in 8 (26.7%) patients. Blood pressure was normal in all our study subjects. Conclusion: In our setting, no gender preponderance of NF-1 was noted. Conjunctival freckling, an ocular pigmentary observation, was a new observation detected in 10% of our study subjects. An association of conjunctival neurofibroma along with cutaneous neurofibromas was seen in 2 (6.7%) patients. Rare radiographic findings like lytic lesions over skull bones and ribboning of metatarsal bones and ribs were detected in 2 (6.7%), 1 (3.3%) and 3 (10%) patients, respectively.

How to cite this article:
Lakshmanan A, Bubna AK, Sankarasubramaniam A, Veeraraghavan M, Rangarajan S, Sundaram M. A clinical study of neurofibromatosis-1 at a tertiary health care centre in south India.Pigment Int 2016;3:102-107

How to cite this URL:
Lakshmanan A, Bubna AK, Sankarasubramaniam A, Veeraraghavan M, Rangarajan S, Sundaram M. A clinical study of neurofibromatosis-1 at a tertiary health care centre in south India. Pigment Int [serial online] 2016 [cited 2022 Aug 13 ];3:102-107
Available from: https://www.pigmentinternational.com/text.asp?2016/3/2/102/196302

Full Text


Neurofibromatosis (NF)-1 is an autosomal dominant disorder affecting many body systems. It is seen to have affected almost 1 in 3500 individuals[1] and has been associated with a wide variety of manifestations with a number of new presentations being discovered.[2],[3],[4],[5] We therefore conducted this study to elaborate the clinical findings encountered in NF-1 and detect whether new features were identifiable amongst our study subjects.


Our study was conducted in the department of Dermatology of Sri Ramachandra University. This was an observational study conducted over a one year period. A total of 30 patients diagnosed with NF-1 after fulfilling the National Institute of Health (NIH) criteria were selected for our study, following a written and informed consent from each participant. From each patient a relevant history was obtained, followed by assessment of vital parameters and performing dermatologic, ophthalmologic, orthopaedic, dental and otorhinolaryngology examinations. After these workups, each patient had a skin biopsy done from the neurofibroma on the skin. Other investigations performed included X-ray skull P-A view, ultrasonography of the abdomen, computerized tomography of the skull in selected patients, orthopentamogram, tuning fork tests and an audiometry test. In patients suspected with kyphoscoliosis and lower limb deformities, X-ray of the spine and lower limbs were also taken. Once all findings were obtained, observations for the same were recorded. As all values were quantitative, they were expressed as percentage values.


Out of the 30 patients, 14 (46.7%) were males and 16 (53.3%) were females. The youngest patient in our series was 8 years old and the oldest patient encountered was aged 77 years. Only 10 (33.3%) patients had a family history of NF-1. The remaining 20 (66.7%) patients were the first affected in the family.

Café-au-lait macules (CALMs) were identified in 28 (93.3%) patients [Figure 1]. In all these patients, CALMs were present since birth. In the remaining 2 (6.7%) patients, no CALMs were identified till date.{Figure 1}

Freckling over the body was demonstrable in all patients of our study. The specific location of freckles over the body with their requisite frequencies has been lucidly elucidated in [Table 1].{Table 1}

Cutaneous neurofibromas were encountered in all our patients [Figure 1]. In 26 (86.6%) patients, it was the nodular variety that was elaborated, and in 1 (3.3%) patient, it was the plexiform variant that was seen. In the remaining 3 (10%) patients, both nodular and plexiform types of neurofibromas were demonstrable. Nodular neurofibromas (NN) in our study subjects demonstrated a diffuse distribution over the trunk and extremities. Plexiform neurofibromas (PN) however were more localized. In 2 patients, they were present over the face, and in the remaining 2 patients, trunk involvement was encountered.

Ocular findings encountered in our series included Lisch nodules in 28 (93.3%) patients [Figure 2], conjunctival neurofibromas in 2 (6.7%) patients [Figure 3] and conjunctival freckling in 3 (10%) patients.{Figure 2}{Figure 3}

Blood pressure depicted normal values in all our study subjects.

Kyphoscoliosis was observed in 7 (23.3%) patients, tibial pseudarthrosis in 2 (6.7%) patients and precocious puberty in 2 (6.7%) patients.

Mental retardation (MR) was observed in only 3 (10%) patients of our study. In the remaining 27 (90%) patients, the intelligence quotient was within normal limits.

Oral lesions identified in our study were lip neurofibroma in 3 (10%) patients and neurofibroma on the tongue in 1 (3.3%) patient. In 2 (6.7%) patients, orthopentomogram revealed widening of the mandibular canal. No significant conclusion could be derived regarding the oral hygiene of our study subjects, because even normal individuals belonging to the same socio-economic class (as our study population) present with a substantially poor oral hygiene.

Radiography of the skull demonstrated lytic lesions in 2 (6.7%) patients [Figure 4], ribboning of ribs in 3 (10%) patients [Figure 5] and ribboning of metatarsals in 1 (3.3%) patient [Figure 6].{Figure 4}{Figure 5}{Figure 6}

Other findings encountered were anaemia in 1 (3.3%) patient, systemic lupus erythematosus (SLE) in 1 (3.3%) patient, facial asymmetry in 2 (6.7%) patients and palmoplantar keratoderma (PPK) in 1 (3.3%) patient.


NF-1 is diagnosed by the following criteria enumerated by NIH[1] that include:

Six or more CALMs (>5 mm pre-puberty, >15 mm post-puberty)Two or more neurofibromas of any type, or one or more plexiform neurofibromaFreckling in the axilla or groinOptic gliomaTwo or more Lisch nodulesDysplasia of the sphenoid or thinning of long bone cortexFirst-degree relative with NF-1

For a patient to be considered as having NF-1, at least two or more of these criteria should be present in the patient concerned. In our study, on the basis of the aforementioned criteria, the patients were diagnosed as NF-1.

In NF-1, there usually is no gender predominance.[6] In our study too, no sex was associated with an increased prevalence of NF-1. Even so, the gender characteristics of studies by McKeever et al.[6] and Poyhonen et al.[7] were in consonance with our findings. However, in a Nigerian study,[8] a definitive male preponderance of 70.4% was noted.

CALMs were seen in 93.3% of our participants [Figure 1]. This was at par with almost all prior studies in this regard that demonstrated the occurrence of CALMs in 79–100% of their patients.[9],[10],[11],[12],[13],[14],[15],[16]

Freckling was observed in all patients in our series. Our figures were much higher when compared to the frequency of freckling in previous studies that ranged from 60 to 87%.[9],[10],[11],[12],[13],[14],[15],[16] Apart from cutaneous freckling, conjunctival freckling was also identified in 3 (10%) patients, which is a new finding in our study. Whether the increased frequency of freckling seen in our study subjects had a relationship with the Indian skin type, differing from Caucasian skins in terms of gene penetrance regarding this feature, needs further elaboration.

In our study population, only 33.3% of the patients demonstrated a positive family history of NF-1. The remaining 66.7% patients were the first to be affected in their family. Our values here were significantly lower when compared to previous studies, wherein familial association ranged from 43 to 71%.[15],[16] This reduced association could be linked to under-reporting in our set-up.

The occurrence of PN in our study was 13.3%. This was almost at par with the findings of McGaughran et al.,[15] and Borberg,[9] who depicted PN in 15 and 16% of their patients, respectively. In other studies however, the prevalence ranged from 19 to 34%,[16] except for the study by Odebode et al.,[8] wherein the prevalence of PN in their study subjects was a mere 8.2%.

NN [Figure 1] on the other hand were demonstrated in 96.6% of our study subjects, almost at par with the findings of Wolkenstein et al.,[12] who depicted an occurrence of 91% for NN in their study, and Odebode et al.,[8] who observed a 100% occurrence for the same. Other authors however witnessed NN in 40–83% of their study subjects.[10],[11]

A new finding of the presence of neurofibromas in the palpebral conjunctiva was seen in 2 (6.7%) patients [Figure 2] of our study population. Though isolated conjunctival neurofibromas have been reported in the past,[17],[18],[19] its occurrence in patients with NF-1 has not been previously reported. The authors therefore would like to highlight this new finding.

Iris hamartomas or LN [Figure 3], a characteristic finding of NF-1, was detected by slit lamp examination in 93.3% of our study subjects. Our findings were almost at par with that of a Welsch study,[10] demonstrating LN in 87% of their study subjects. In other studies though the prevalence ranged from 52 to 84%, thereby making us conclude regarding the wide range of the occurrence of LN in patients of NF-1.

Kyphoscoliosis was demonstrated in 7 (23.3%) of our study subjects. Our values here were much higher than the findings of Huson et al.[10] and Poyhonen,[16] who demonstrated kyphoscoliosis to occur in 4 and 2% of their patients, respectively.Tibial pseudarthrosis was seen in 2 (6.7%) patients of our study. Our values were slightly higher when compared to previous studies wherein the occurrence ranged from 2 to 3%.[14],[16] Whether there appears a role of superimposed environmental factors needs further identification, because nearly all previous studies were from western literature with a dramatic difference in the local topography.

Our findings for precocious puberty was 6.7% in our patient series, the value again being higher than those from previous studies by Friedman and Birch[14] and Poyhonen.[16]

MR was seen in 3 (10%) patients. Our values were much higher when compared to the findings of Poyhonen,[16] who demonstrated a value of 5% in their patients, and Huson et al.,[10] in whose study MR was identified in only 3% of their patients.

Bathing trunk melanocytic nevus was observed in 2 (6.7%) patients of our series. This was almost at par with the findings of Wander and Das Gupta.[20]

Sphenoidal bone dysplasia was identified in 4 (13.3%) of our patients. Our values were much higher when compared to the findings of Friedman and Birch,[14] and Poyhonen.[16]

Ribboning of ribs was identified in 3 (10%) patients [Figure 4], ribboning of metatarsals in 1 (3.3%) patient [Figure 5] and lytic lesions over the skull bones in 2 (6.7%) patients [Figure 6] on radiography. These were new findings detected by the authors on radiology in their series. Only further studies in this regard could enable a concrete delineation whether these were coincidental findings or an attribute related to NF-1.

Lastly, we encountered PPK in 1 (3.3%) patient and SLE in 1 (3.3%) patient. Now whether this was a coincidence or a clear-cut association again remains a subject of discussion.


To conclude, we find that there appears to be a wide range of associations related to NF-1. As there in no permanent cure for NF-1, the importance of a proper psychologic counselling cannot be under-estimated along with the introduction of appropriate genetic counselling in all patients planning for future conception. With an increased risk of bony abnormalities and a tendency for developing neurofibrosarcoma in some patients, the need for a proper follow-up needs to be emphasized upon by all clinicians. In our study, we were able to detect a few new features in our NF-1 patients like presence of conjunctival neurofibromas along with cutaneous neurofibromas, conjunctival freckles, lytic lesions over the skull bones and ribboning of the ribs and metatarsals in some of our patients. Therefore, to contemplate, there actually could be many more new features in NF-1 that may require further elucidation. As almost all studies with reference to NF-1 are from western literature and with paucity of literature for the same from India, more studies in relation to NF-1 from the Indian subcontinent would help to further delineate features more common in our set-up and their differences with respect to our Caucasian counterparts.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


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