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Year : 2018  |  Volume : 19  |  Issue : 1  |  Page : 86-88

Legius syndrome

Department of Dermatology, Venereology and Leprology, Government Medical College, Kota, Rajasthan, India

Date of Web Publication28-Dec-2017

Correspondence Address:
Suresh Kumar Jain
Department of Dermatology, Venereology, Leprology, Government Medical College, Kota - 324 001, Rajasthan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpd.IJPD_143_16

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How to cite this article:
Sharma MK, Kumar R, Gupta S, Jain SK. Legius syndrome. Indian J Paediatr Dermatol 2018;19:86-8

How to cite this URL:
Sharma MK, Kumar R, Gupta S, Jain SK. Legius syndrome. Indian J Paediatr Dermatol [serial online] 2018 [cited 2020 Oct 29];19:86-8. Available from: https://www.ijpd.in/text.asp?2018/19/1/86/206072


Legius syndrome, also known as neurofibromatosis (NF) type 1-like syndrome, is a rare, genetic skin pigmentation disorder characterized by multiple café au lait macules (CALMs) with or without axillary or inguinal freckling. Other NF1-associated features such as Lisch nodules, neurofibromas, NF1-specific bone lesions, optic pathway gliomas, and malignant peripheral nerve sheath tumors are absent. Herein, we describe a case of a 16-year-old male presenting with multiple CALMs and axillary freckling.

A 16-year-old male presented to us with multiple hyperpigmented lesions predominantly on the left side of chest and back for the last 2 years. The lesions increased gradually in number. Family history was positive for similar lesions in his mother. On cutaneous examination, the patient had multiple CALMs of approximately size 15 mm, predominantly over the left upper chest, back, and arm [Figure 1]. Furthermore, axillary freckling was present on the left side [Figure 2]. Other features of NF were analyzed. Lisch nodules in iris and neurofibroma were absent. Lisch nodules were examined on slit-lamp examination. Systemic examination revealed no abnormality.
Figure 1: Multiple café au lait macules on the left upper chest

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Figure 2: Axillary freckling

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Routine investigations including complete blood count, liver function tests, renal function tests, and electrocardiogram were normal. Computed tomography (CT) of head and neck was normal.

Other autosomal dominant diseases presenting with CALMs were excluded because of the lack of other associated manifestations. The NF1 was ruled out by the absence of Lisch nodules in iris, neurofibromas, and optic glioma on CT head. NF5 was ruled out by the absence of neurofibroma. NF6 was ruled out by the presence of axillary freckling. NF-6 is characterized by only multiple CALMs. Features of  McCune-Albright syndrome More Details, characterized by multiple endocrinopathies, in particular precocious puberty and polyostotic fibrous dysplasia, were absent. The absence of lentigines ruled out  LEOPARD syndrome More Details. Other features of LEOPARD syndrome are electrocardiography conduction abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retarded growth, and sensorineural deafness. Based on clinical findings of multiple CALMs and axillary freckling along with the lack of other features of NF1, diagnosis of Legius syndrome was made.

Legius syndrome or NF1-like syndrome is a rare, autosomal dominant genetic skin pigmentation disorder. The clinical presentation of Legius syndrome is similar to that of NF1, characterized by multiple CALMs with or without axillary or inguinal freckling. Other NF1-associated features such as Lisch nodules, neurofibromas, NF1-specific bone lesions, optic pathway gliomas, and malignant peripheral nerve sheath tumors are absent. Additional clinical features have been reported in Legius syndrome: pectus excavatum[1],[2],[3],[4] or carinatum and unilateral postaxial polydactyly.[1],[3] Lipomas can present in some individuals with Legius syndrome.[3],[5] Learning disabilities and behavioral problems are also possible manifestations of the disease.[6] The differential diagnosis is shown in [Table 1].
Table 1: Differential diagnosis of legius syndrome

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The syndrome was first described in 2007 by Brems et al.,[7] who identified that a heterozygous mutation in SPRED1 gene was responsible for this mild NF phenotype. Several SPRED1 variants, including sequence-based changes and large deletions/duplications, have been linked to Legius syndrome.[8],[9]

The case is being presented due to its rarity and only a few cases have been reported.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Denayer E, Chmara M, Brems H, Kievit AM, van Bever Y, Van den Ouweland AM, et al. Legius syndrome in fourteen families. Hum Mutat 2011;32:E1985-98.  Back to cited text no. 1
Laycock-van Spyk S, Jim HP, Thomas L, Spurlock G, Fares L, Palmer-Smith S, et al. Identification of five novel SPRED1 germline mutations in Legius syndrome. Clin Genet 2011;80:93-6.  Back to cited text no. 2
Messiaen L, Yao S, Brems H, Callens T, Sathienkijkanchai A, Denayer E, et al. Clinical and mutational spectrum of neurofibromatosis type 1-like syndrome. JAMA 2009;302:2111-8.  Back to cited text no. 3
Spencer E, Davis J, Mikhail F, Fu C, Vijzelaar R, Zackai EH, et al. Identification of SPRED1 deletions using RT-PCR, multiplex ligation-dependent probe amplification and quantitative PCR. Am J Med Genet A 2011;155A: 1352-9.  Back to cited text no. 4
Pasmant E, Sabbagh A, Hanna N, Masliah-Planchon J, Jolly E, Goussard P, et al. SPRED1 germline mutations caused a neurofibromatosis type 1 overlapping phenotype. J Med Genet 2009;46:425-30.  Back to cited text no. 5
Denayer E, Descheemaeker MJ, Stewart DR, Keymolen K, Plasschaert E, Ruppert SL, et al. Observations on intelligence and behavior in 15 patients with Legius syndrome. Am J Med Genet C Semin Med Genet 2011;157C:123-8.  Back to cited text no. 6
Brems H, Chmara M, Sahbatou M, Denayer E, Taniguchi K, Kato R, et al. Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. Nat Genet 2007;39:1120-6.  Back to cited text no. 7
Brems H, Legius E. Legius syndrome, an Update. Molecular pathology of mutations in SPRED1. Keio J Med 2013;62:107-12.  Back to cited text no. 8
Brems H, Pasmant E, Van Minkelen R, Wimmer K, Upadhyaya M, Legius E, et al. Review and update of SPRED1 mutations causing Legius syndrome. Hum Mutat 2012;33:1538-46.  Back to cited text no. 9


  [Figure 1], [Figure 2]

  [Table 1]


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