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Year : 2018  |  Volume : 19  |  Issue : 3  |  Page : 263-265

A child with multiple café au lait macules: Rare presentation of plexiform neurofibromatosis with facial dysmorphism, alopecia, proptosis, stridor, and limb length discrepancy

1 Department of Pediatric Medicine, Institute of Child Health, Kolkata, West Bengal, India
2 Department of Pediatric Dermatology, Institute of Child Health, Kolkata, West Bengal, India

Date of Web Publication28-Jun-2018

Correspondence Address:
Dr. Aniruddha Ghosh
Department of Pediatric Medicine, Institute of Child Health, No. 11, Dr. Biresh Guha Street, Kolkata - 700 017, West Bengal
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpd.IJPD_12_17

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Multiple café au lait macules are one of the cornerstones in diagnosing neurofibromatosis Type 1 (NF 1). NF 1 is often a multisystem neurocutaneous disorder, plexiform NF being one of the most important variants of this phacomatosis. Here, a rare case of a 2.5-year-old male child without positive family history has been described who presented with multiple large café au lait spots, alopecia, dysmorphic facies, proptosis, protrusion and deviation of tongue, biphasic stridor, bilateral neck swelling, and abnormal gait due to foreshortened left leg. Magnetic resonance imaging revealed abnormal soft-tissue infiltration of cavernous sinus through sphenoid bone, retro-orbital, retropharyngeal, parapharyngeal spaces, floor of mouth, and encasement of unilateral neck vessels and compression over trachea. Indirect laryngoscopy revealed unilateral vocal cord palsy most likely due to recurrent laryngeal nerve involvement. Biopsy confirmed the diagnosis of NF. Pediatricians and dermatologists should be aware of syndromic causes and their varied presentations while encountering a child with multiple large café au lait spots.

Keywords: Alopecia, café au lait macule, neurofibromatosis Type I, plexiform neurofibroma, proptosis

How to cite this article:
Ghosh A, Kundu P, Dhar S, Bhattacharya A. A child with multiple café au lait macules: Rare presentation of plexiform neurofibromatosis with facial dysmorphism, alopecia, proptosis, stridor, and limb length discrepancy. Indian J Paediatr Dermatol 2018;19:263-5

How to cite this URL:
Ghosh A, Kundu P, Dhar S, Bhattacharya A. A child with multiple café au lait macules: Rare presentation of plexiform neurofibromatosis with facial dysmorphism, alopecia, proptosis, stridor, and limb length discrepancy. Indian J Paediatr Dermatol [serial online] 2018 [cited 2020 Oct 29];19:263-5. Available from: https://www.ijpd.in/text.asp?2018/19/3/263/206057

  Introduction Top

Neurofibromatosis Type 1 (NF1) is a neurocutaneous syndrome first described by Friedrich von Recklinghausen in 1882.[1] This disorder is often progressive and often leads to physical deformities and neurological disabilities. Amid the several variants (around 8) of NF described in literature till date, NF1 or von Recklinghausen's disease is most common and it is characterized by skin changes such as café au lait macules and axillary freckling (Crowe sign) and neurofibromas arising from nonmyelinating type Schwann cells as a result of autosomal dominant or sporadic mutations of NF1 gene located at chromosome 17q11.2.[2] Plexiform neurofibromas, found in 30% cases of NF1, originate from visceral as well as peripheral nerves simultaneously and also infiltrate surrounding tissues and organs often giving a clinical impression of “bags of worms.”[3] We report a rare case of NF1 with several uncommon features.

  Case Report Top

A 2-year, 5-month-old male child, the only offspring born out of a nonconsanguineous marriage, presented with multiple large hyperpigmented skin lesions all over the body and gradual swelling of right side of face and neck since birth, noisy breathing with cough, protrusion of the tongue from oral cavity, and limping while walking for 1 year. All the symptoms were insidious in onset and gradually progressive. The child snored loudly while sleeping, family history, perinatal history – all were normal. There was no history of fever, dysphagia, generalized weakness, bleeding tendency, recurrent infections, blood transfusion, bone/joint pain, etc.

On examination, right half of face was swollen with proptosis of right eye [Figure 1] and distorted vertical slit-like small external acoustic meatal opening. Vision, hearing, etc., were clinically normal. There was protrusion of tongue with tip deviated toward left [Figure 1]. To the right side of frenulum of tongue, there was ill-defined swelling. Both sides of the neck were diffusely swollen, but the right side was more prominent extending to right shoulder. All the areas of the swelling were nonpulsatile, noncompressible, nontender, and firm and at places of thick cord-like consistency. No bruit was heard, and transillumination test was negative. There was biphasic stridor at rest and the child had hoarse voice. He had to limp while walking due to limb length discrepancy (left leg longer than right leg by 5 cm). Vital parameters were stable in spite of stridor. There was no organomegaly. Air entry was normal in all the areas of chest and back. Cardiovascular, central nervous system was within normal limits. Development was appropriate for age.
Figure 1: Enlargement of the right side of face and neck with proptosis, protrusion, and deviation of tongue due to mass on the right side of frenulum and alopecia over frontal region of scalp

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Interestingly, the patient had several (>10 in number) well-circumscribed, evenly pigmented macules and patches of >20 cm size over both sides of the neck, trunk, and posterior aspect of left leg and ankle [Figure 2] and [Figure 3]. These were identified as large segmental café au lait macules and patches.
Figure 2: Large segmental café au lait macule with irregular margin on the right side of neck

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Figure 3: Café au lait macule over posterior aspect of lower part of overgrown left leg

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Routine investigations including hematological parameters were within normal ranges. Ophthalmological checkup, brainstem auditory evoked potential test, echocardiography, chest X-ray, and ultrasonogram of abdomen were within normal limits. Indirect laryngoscopy revealed palsy of right vocal cord indicating involvement of right recurrent laryngeal nerve. X-ray of the lower part of left tibia showed cortical thickening corresponding clinically with overlying hyperpigmented patch topographically.

Magnetic resonance imaging of the head and neck including upper part of thorax revealed extensive soft tissue lesion starting below from superior mediastinum compressing over right side of trachea and larynx, encasing right-sided neck vessels, and also infiltrating continuously the para- and retro-pharyngeal spaces including right side of floor of oral cavity proper, right retro-orbital space and extending above up to the right cavernus sinus by destroying part of sphenoid bone. Excision biopsy taken from the right side of neck swelling confirmed diagnosis of NF.

Surgical exploration was attempted to relieve the airway compression, but unfortunately, the patient succumbed after 3 days of operation.

  Discussion Top

NF1 has an incidence of 1:3000.[2] In this disorder, neurofibromin, a protein responsible for retrovirus-associated DNA sequence-mediated cell growth signaling pathway, is not produced as a result of mutation which gives rise to an array of clinical features.[3]

Skin is the most common organ affected in NF1. Café au lait macules, present in nearly 95% NF1 patients since birth,[4] occur in various sizes all over the body. These nests of pigmented melanocytes are of neuroectodermal in origin and often seen in dermatomal distribution.[5] The name comes from their typical coffee and milk hue. There are two subtypes clinically: Most common ones with regular and well-demarcated “Coast of California” margins, with varied sizes and numbers and second, less frequent solitary larger lesions with irregular “Coast of Maine” border.[6] These macules increase in number and size until puberty.[6] Found in 5%–15% normal children, café au lait macules are taken as indicator of NF 1 if six/more macules of size >5 mm (in prepubertal)/>15 mm (in postpubertal) are present.[7] Other syndromes associated with café au lait include McCune–Albright syndrome, Legius syndrome, Noonan syndrome, other neuro-cardio-facial-cutaneous syndromes, ring chromosome syndromes, and constitutional mismatch repair deficiency syndrome.[6] Apart from large multiple café au lait macules of first subtype, our patient also had alopecia over frontal region and temple of the head. Macias et al.[8] speculated that alopecia may occur in NF as dermal infiltration by diffuse neurofibroma surrounds and pushes hair follicles toward upper dermis.

Craniomaxillofacial plexiform NF has three subtypes: massive plexiform, cranioorbital, and cervical.[9] Clinical features vary widely including ocular involvement hampering eye movement, dyspnea from upper airway obstruction, cranial nerve involvement, and facial disfigurement.[9] Greater wing of sphenoid hypoplasia results into orbital asymmetry and in severe forms, proptosis.[10] Our patient had facial asymmetry, proptosis, airway problem due to unilateral vocal cord paralysis, and tracheal compression from outside.

Skeletal system involvement in NF1 is common and often progressive and is characterized by scoliosis, kyphosis, pseudarthrosis of long bones, sphenoid wing hypoplasia, etc. Unilateral overgrowth, as found in our case, can occur over time involving arms or lower leg.[4]

Diagnosis of NF1 is achieved when patient meets two or more criteria developed by the National Institute of Health.[7] Biopsy, as in our case, is performed to exclude malignant transformation in plexiform NF.

Treatment of plexiform NF is surgery. The aim is to correct deformity and reduce malignant tissue where transformation to malignancy occurs. However, often, these masses are nonresectable and they recur in 20% cases. Some centers prefer interferon alpha over surgery nowadays in nonresectable cases.[9]

Life expectancy is reduced in these patients due to malignant transformation and cardiovascular diseases.[2]

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.


We sincerely thank Dr. Jaydeep Choudhury and Dr. Maya Mukhopadhyay for their valuable help.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Ruggieri M. The different forms of neurofibromatosis. Childs Nerv Syst 1999;15:295-308.  Back to cited text no. 1
Evans DG, Howard E, Giblin C, Clancy T, Spencer H, Huson SM, et al. Birth incidence and prevalence of tumor-prone syndromes: Estimates from a UK family genetic register service. Am J Med Genet A 2010;152A:327-32.  Back to cited text no. 2
Kleihues P, Louis DN, Scheithauer BW, Rorke LB, Reifenberger G, Burger PC, et al. The WHO classification of tumors of the nervous system. J Neuropathol Exp Neurol 2002;61:215-25.  Back to cited text no. 3
Ferrari A, Bisogno G, Macaluso A, Casanova M, D'Angelo P, Pierani P, et al. Soft-tissue sarcomas in children and adolescents with neurofibromatosis type 1. Cancer 2007;109:1406-12.  Back to cited text no. 4
Weston JA. Neural crest cell migration and differentiation. UCLA Forum Med Sci 1971;14:1-22.  Back to cited text no. 5
Aase JM. Diagnostic Dysmorphology. 2nd ed. London, New York: Plenum Medical Book Company; 1990. p. 299.  Back to cited text no. 6
Neurofibromatosis. Conference statement. National Institutes of Health consensus development conference. Arch Neurol 1988;45:575-8.  Back to cited text no. 7
Macias VC, Rafael M, Fernandes C, Rosa JC. Diffuse neurofibroma – An uncommon cause of alopecia. An Bras Dermatol 2013;88 6 Suppl 1:166-9.  Back to cited text no. 8
Citak EC, Oguz A, Karadeniz C, Okur A, Memis L, Boyunaga O. Management of plexiform neurofibroma with interferon alpha. Pediatr Hematol Oncol 2008;25:673-8.  Back to cited text no. 9
Macfarlane R, Levin AV, Weksberg R, Blaser S, Rutka JT. Absence of the greater sphenoid wing in neurofibromatosis type I: Congenital or acquired: Case report. Neurosurgery 1995;37:129-33.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3]


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