Home About us Editorial board Ahead of print Current issue Archives Instructions Submit article Search Subscribe Contacts Login
  • Users Online: 496
  • Home
  • Print this page
  • Email this page


 
 Table of Contents  
CASE REPORT
Year : 2018  |  Volume : 5  |  Issue : 1  |  Page : 50-53

Segmental giant café au lait macule in neurofibromatosis 1


Department of Dermatology, Venereology and Leprology, Government Medical College & Hospital, Nagpur, Maharashtra, India

Date of Web Publication29-May-2018

Correspondence Address:
Kinjal D Rambhia
c/o Dr. Amit Gulati, H. No. 574, Gulati Bhavan, Mukundraj Lane, Walker Road, Mahal, Nagpur, Maharashtra
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/Pigmentinternational. Pigmentinternational

Rights and Permissions
  Abstract 


A 2-year-old male child born of third degree consanguineous marriage was brought to dermatology outpatient department with multiple dark colored flat lesions over body and one large dark colored flat lesion over right side of body since birth. Another prominent feature was proptosis of left eye since 1 month. Cutaneous examination revealed multiple café au lait macules (CALMs) over lower limbs and back and large CALM over right side of back, chest, and upper limb with proptosis of left eye. Histopathological examination of large patch findings was suggestive of CALM. Magnetic resonance imaging (MRI) brain plain and contrast findings were suggestive of plexiform neurofibroma. Based on clinical features and investigations a diagnosis of giant CALM in segmental distribution in a case of neurofibromatosis 1 (NF1) was made. It can be explained on basis of type II segmental manifestation in NF1.

Keywords: Giant segmental cafe au lait macule, neurofibromatosis 1, type II segmental manifestation


How to cite this article:
Supekar BB, Rambhia KD, Mukhi JI, Singh RP. Segmental giant café au lait macule in neurofibromatosis 1. Pigment Int 2018;5:50-3

How to cite this URL:
Supekar BB, Rambhia KD, Mukhi JI, Singh RP. Segmental giant café au lait macule in neurofibromatosis 1. Pigment Int [serial online] 2018 [cited 2018 Dec 17];5:50-3. Available from: http://www.pigmentinternational.com/text.asp?2018/5/1/50/233465




  Introduction Top


Neurofibromatosis 1 (NF1, von Recklinghausen’s neurofibromatosis) is a rare autosomal dominant disorder characterized by café au lait macules (CALMs), cutaneous or extracutaneous neurofibroma, axillary or inguinal freckling, optic glioma, iris lisch nodules, skeletal dysplasia or affected first degree relatives.[1],[2] It is associated with postzygotic mutation in the NF1 gene 1 on the long arm of chromosome 17 leading to somatic mutation.[3]

Happle proposed two forms of segmental manifestations in autosomal dominant disorders namely NF1 and tuberous sclerosis.[4],[5] According to which, in NF1, type I manifestations represents segmental neurofibromatosis (SNF) and type II manifestations represents segmental disease superimposed on classical generalized disease.[4],[5]


  Case report Top


A 2-year-old male child born of third degree consanguineous marriage was brought to dermatology outpatient department with multiple hyperpigmented macules with regular margins over back and thigh since birth [[Figure 1]a and b]. He also had a large hyperpigmented patch with regular border in segmental distribution (>30 cm) over right side of chest and back and right upper limb [[Figure 2]a and b]. There was proptosis of left eye [[Figure 3]a]. Axillary and inguinal freckling, cutaneous neurofibroma were absent. Palms, soles, hair, nails, oral cavity, dentition were normal. Kyphoscoliosis, tibial bowing were absent. No history of mental retardation or seizures. Neurological examination and developmental milestones were normal. None of family members had any findings suggestive of neurofibromatosis.
Figure 1: (a) and (b) Multiple CALMs with regular margins over back and thigh

Click here to view
Figure 2: (a) and (b) A large CALM with regular border in segmental distribution

Click here to view
Figure 3: (a) Proptosis of left eye. (b) MRI brain showing ill-defined area of altered intensity noted over left upper eyelid and extraconal compartment on superotemoral aspect of left orbit with minimal inferior displacement of left eyeball

Click here to view


Considering these clinical features, the differential diagnoses were NF1 and McCune–Albright syndrome.

Routine investigations were normal. On ophthalmic examination, lisch nodules were absent. No X-ray findings suggestive of fibrous dysplasia of bone were noted. Histopathological examination of large patch revealed basal hyperpigmentation with increased focal basal melanocytes which was suggestive of CALM.

Magnetic resonance imaging (MRI) brain, plain and contrast revealed ill-defined area of altered signal intensity noted involving left upper eye lid and extraconal compartment of left orbit with minimal inferior displacement of left eyeball possibly plexiform neurofibroma measuring 0.7 cm × 2 cm × 1.8 cm [[Figure 3]b].

Based on clinical features and investigations, a diagnosis of NF1 with giant segmental CALM was made. Genetic counseling was advised to parents. Patient was referred to pediatrician and neurologist for examination and was asked to follow up in our Outpatient department (OPD).


  Discussion Top


NF1 (von Recklinghausen disease) is a rare autosomal dominant disorder characterized by CALMs, cutaneous or extracutaneous neurofibroma, axillary or inguinal freckling, optic glioma, iris lisch nodules, skeletal dysplasia or affected first degree relatives.[1],[2]

Multiple CALMs are observed in genetic diseases like NF1, McCune–Albright syndrome and Noonan’s syndrome.[6] CALMs are sharply defined, light-brown patches that vary in size from 0.5 to 50 cm, although the majority are 10 cm or less in size. Giant CALMs larger than 30 cm since birth are not usual.[2]

SNF is defined as CALMs or neurofibromas in a single, unilateral segment of the body.[3],[7] These lesions do not cross midline.[3],[7] There is no family history. Systemic involvement is rare. Type I segmental manifestations of NF1 represent SNF.[5] In SNF, mutation occurs late during the embryonic development that provokes localized disease.[4],[5]

Type II manifestations which occurs due to loss of heterozygosity (LOH) that occurs at an early stage of embryogenesis.[4],[5],[8] It manifests as segmental disease may be superimposed on classical generalized disease. Type II segmental manifestation of autosomal dominant dermatoses characterized by pronounced segmental lesions superimposed on the ordinary nonsegmental phenotype.[4],[5] Type II manifestations have been reported in the form of plexiform neurofibroma and giant CALM in NF1.[9],[10],[11]

LOH is the segmental loss of remaining allele which may give rise to segments of body with exaggerated presentation of autosomal dominant conditions. Patients who present with SNF with axillary freckling, CALMs or lisch nodule are explained on the basis of LOH than mosaicism. The risk of passing gene to child is 50:50.[8]

We describe a case of NF1 in child with a giant CALM. Giant CALM in NF1 can be explained on the basis of type II segmental manifestations of autosomal dominant disorders.

This case describes rare finding of NF1 with additional findings of segmental giant CALM.

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

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Stumpf DA, Alksne JF, Annegers JF, Brown SS, Conneally PM, Housman D et al. NIH consensus development conference: Neurofibromatosis conference statement. Arch Neurol 1988;45:575-83.  Back to cited text no. 1
    
2.
Yang CC, Happle R, Chao SC, Yu-Yun Lee J, Chen W. Giant café-au-lait macule in neurofibromatosis 1: A type 2 segmental manifestation of neurofibromatosis 1? J Am Acad Dermatol 2008;58:493-7.  Back to cited text no. 2
    
3.
Tinschert S, Naumann I, Stegmann E, Buske A, Kaufmann D, Thiel G et al. Segmental neurofibromatosis is caused by somatic mutation of the neurofibromatosis type 1 (NF1) gene. Eur J Hum Genet 2000;8:455-91.  Back to cited text no. 3
    
4.
Happle R. Loss of heterozygosity in human skin. J Am Acad Dermatol 1999;41:143-61.  Back to cited text no. 4
    
5.
Happle R. A rule concerning the segmental manifestation of autosomal dominant skin disorders: Review of case reports providing evidence for dichotomous types of severity. Arch Dermatol 1997;133:1505-9.  Back to cited text no. 5
    
6.
Erdi H, Boyvat A, Calikoglu E. Giant café au lait spot in a patient with neurofibromatosis. Acta Derm Venereol 1999;79:496.  Back to cited text no. 6
    
7.
Ruggieri M, Huson SM. The clinical and diagnostic implications of mosaicism in the neurofibromatoses. Neurology 2000;56:1433-43.  Back to cited text no. 7
    
8.
James WD. Genodermatoses and congenital anomalies. Andrew’s Diseases of the Skin Clinical Dermatology, 11th ed. USA: Elsevier 2011. p. 538.  Back to cited text no. 8
    
9.
Thappa DM, Jeevankumar B, Karthikeyan K. Giant café-au-lait macule in neurofibromatosis type 1. J Dermatol 2001;28:60-1.  Back to cited text no. 9
    
10.
Happle R. Large plexiform neurofibromas may be explained as a type 2 segmental manifestation of neurofibromatosis type 1. Am J Med Genet 2001;98:363-4.  Back to cited text no. 10
    
11.
Archer CB, Glover M, Atherton DJ. Segmental neurofibromatosis with generalized café au lait spots. Br J Dermatol 1988;119(Suppl 33):96.  Back to cited text no. 11
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

 
  In this article
Abstract
Introduction
Case report
Discussion
References
Article Figures

 Article Access Statistics
    Viewed601    
    Printed15    
    Emailed0    
    PDF Downloaded72    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]