Jump to comment:

• Multiple café-au-lait macules and Legius syndrome
  Eric Legius
  Published on: 30 August 2019

• Published on: 30 August 2019

  Multiple café-au-lait macules and Legius syndrome

  • Eric Legius, Clinical geneticist University Hospitals Leuven and University of Leuven, Belgium

  Dear authors,
  I read with great interest your article on multiple café-au-lait macules and movement disorder (1). I want to point out that probably an error happened during formatting of table 1. The term RASopathies is used to refer to a group of diseases caused by a mutation in a gene coding for a key component of the RAS-pathway and resulting in hyperactivation of the pathway. This group commonly includes Noonan syndrome, Neurofibromatosis type 1, Legius syndrome, LEOPARD syndrome (now referred to as Noonan syndrome with multiple lentigines), Costello syndrome, CFC syndrome, hereditary gingival fibromatosis, capillary malformation-arteriovenous malformation and Loh syndrome (2). It is confusing to find RASopathies next to Noonan, Legius and LEOPARD syndrome in the same column of table 1. In the same column Legius syndrome is listed as well as NF-like syndrome. Legius syndrome is listed followed by (PTPN11) and NF-like syndrome is followed by the gene (SPRED1). PTPN11 should be listed after Noonan syndrome because it is the most frequent cause of Noonan syndrome and it is not related to Legius syndrome. Legius syndrome is the same as NF1-like syndrome and only one of the two should be listed followed by (SPRED1). In our first publication (3) we named the condition neurofibromatosis 1-like syndrome but later is was renamed Legius syndrome (4).
  Congenital mismatch repair deficiency (CMMRD) is another autosomal recessive condition with café-au-lait macules and...

  Show More

  Dear authors,
  I read with great interest your article on multiple café-au-lait macules and movement disorder (1). I want to point out that probably an error happened during formatting of table 1. The term RASopathies is used to refer to a group of diseases caused by a mutation in a gene coding for a key component of the RAS-pathway and resulting in hyperactivation of the pathway. This group commonly includes Noonan syndrome, Neurofibromatosis type 1, Legius syndrome, LEOPARD syndrome (now referred to as Noonan syndrome with multiple lentigines), Costello syndrome, CFC syndrome, hereditary gingival fibromatosis, capillary malformation-arteriovenous malformation and Loh syndrome (2). It is confusing to find RASopathies next to Noonan, Legius and LEOPARD syndrome in the same column of table 1. In the same column Legius syndrome is listed as well as NF-like syndrome. Legius syndrome is listed followed by (PTPN11) and NF-like syndrome is followed by the gene (SPRED1). PTPN11 should be listed after Noonan syndrome because it is the most frequent cause of Noonan syndrome and it is not related to Legius syndrome. Legius syndrome is the same as NF1-like syndrome and only one of the two should be listed followed by (SPRED1). In our first publication (3) we named the condition neurofibromatosis 1-like syndrome but later is was renamed Legius syndrome (4).
  Congenital mismatch repair deficiency (CMMRD) is another autosomal recessive condition with café-au-lait macules and similar to ataxia telangiectasia it is important to recognize because it is associated with malignancies (5). I suggest to add CMMRD to table 1.

  References
  1 Madaan P, Mukherjee S, Reddy C, et al. Multiple café-au-lait macules and movement disorder: think beyond neurofibromatosis. Arch Dis Child 2019;0:1. doi:10.1136/archdischild-2019-317497
  2 Aoki Y, Niihori T, Inoue S, Matsubara Y. Recent advances in RASopathies. J Hum Genet 2016 ;61:33-9.
  3 Brems H, Chmara M, Sahbatou M,et al. Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. Nat Genet 2007; 39:1120-26.
  4 Stevenson D, Viskochil D Pigmentary findings in neurofibromatosis type 1-like syndrome (Legius syndrome): potential diagnostic dilemmas. JAMA 2009;19:2150-1.
  5 Suerink M, Ripperger T, Messiaen L et al. Constitutional mismatch repair deficiency as a differential diagnosis of neurofibromatosis type 1: consensus guidelines for testing a child without malignancy. J Med Genet 2019;56:53-62.

  Show Less

  Conflict of Interest:
  None declared.

  • Back to top