Hypomelanosis of Ito: A symptom, not a syndrome
Transcript of Hypomelanosis of Ito: A symptom, not a syndrome
Letter to the Editor
Hypomelanosis of Ito: A Symptom, Not a Syndrome
To the Editor:
We would like to comment on the article by Fryburget al. in the American Journal of Medical Genetics [Fry-burg et al., 1996]. In this interesting article, the au-thors state that Hypomelanosis Ito (HI) is a ‘‘well-described neurocutaneous syndrome.’’ We do not thinkthat HI is a single syndrome.
In recent years, several authors have argued that HIis in fact a symptom of a great number of conditions allcharacterized by chromosomal or genetic mosaicism[Donnai et al., 1988; Thomas et al., 1989; Read andDonnai, 1990; Ritter et al., 1990; Ohashi et al., 1992;Sybert, 1994]. The Pallister-Killian syndrome, due toisochromosome 12p mosaicism, is probably the bestknown example [Reynolds et al., 1987]. Recently, wehave surveyed all reports of HI that appeared since thefirst report by Ito (whose patient probably had incon-tinentia pigmenti) [Ito, 1952]. From this survey itemerged that the only constant trait in all reports is adisturbance of pigmentation following the lines of Blas-chko. Such a distribution is caused by cutaneous ge-netic or chromosomal mosaicism [Happle, 1993]. Noother constant abnormalities were found. Although ab-normalities of the central nervous system occur innearly half of all patients, this group of symptoms isitself highly variable. Many different cytogenetic aber-rations have been reported [Donnai et al., 1988; Thom-as et al., 1989 and references therein; Ritter et al.,1990; Ohashi et al., 1992; Sybert, 1994]. Single-geneinheritance has not been demonstrated convincingly[Sybert, 1994]. Considering the above, we think that itis highly unlikely that HI is a syndrome. The hypoth-esis that HI is the cutaneous expression of chromosom-al or genetic mosaicism would seem to be more appro-priate in the light of the available data. The patient ofFryburg et al. has a phenotype suggesting mosaicism:The pigmentary anomalies are in Blaschko lines andthe other abnormalities cluster on the right side of hisbody.
It is still possible that there are single-gene disordersthat cause HI and associated symptoms. However,
these will be hard to find as they will exist in the mo-saic state and not show straightforward AD, AR, orX-linked inheritance. As long as HI is considered a di-agnosis, these cases will be even harder to find, as mo-saicism will be less likely to be searched for when a‘‘diagnosis’’ has already been made.
We think that considering HI as a symptom of mo-saicism would be of great help in recognizing possiblenew conditions that exist only in the mosaic state.
REFERENCES
Donnai D, Read AP, McKeown C, Andrews T (1988): Hypomelanosis of Ito:A manifestation of mosaicism or chimaerism. J Med Genet 25:809–818.
Fryburg JS, Lin KY, Matsumoto J (1996): Abnormal head MRI in a neu-rologically normal boy with hypomelanosis of Ito. Am J Med Genet66:200–203.
Happle R (1993): Mosaicism in human skin. Understanding the patternsand mechanisms. Arch Dermatol 129:1460–1470.
Ito M (1952): Studies on melanin. XI. Incontinentia pigmenti achromians.A singular case of nevus depigmentosus systematicus bilateralis. To-hoku J Exp Med 55 (Suppl):57–59.
Ohashi H, Tsukuhara M, Murano I, Naritomi K, Nishioka K, Miyake S,Kajii T (1992): Pigmentary dysplasias and chromosomal mosaicism:Report of 9 cases. Am J Med Genet 43:716–721.
Read AP, Donnai D (1990): Association of pigmentary anomalies with chro-mosomal and genetic mosaicism and chimerism. Am J Hum Genet47:166–167.
Reynolds JF, Daniel A, Kelly TE, Gollin SM, Stephan MJ, Carey J, AdkinsWN, Webb MJ, Char F, Jimenez JF, Opitz JM (1987): Isochromosome12p mosaicism (Pallister mosaic aneuploidy or Pallister-Killian syn-drome): Report of 11 cases. Am J Med Genet 27:257–274.
Ritter CL, Steele MW, Wenger SL, Cohen BA (1990): Chromosome mosa-icism in hypomelanosis of Ito. Am J Med Genet 35:14–17.
Sybert VP (1994): Hypomelanosis of Ito: A description, not a diagnosis. JInvest Dermatol 103:141S–143S.
Thomas IT, Frias JL, Cantu ES, Lafer CZ, Flannery DB, Graham JG(1989): Association of pigmentary anomalies with chromosomal andgenetic mosaicism and chimerism. Am J Hum Genet 45:193–205.
M.A.M. van Steensel*Department of Human GeneticsUniversity Hospital NijmegenNijmegen, The Netherlands
P.M. SteijlenDepartment of DermatologyUniversity Hospital NijmegenNijmegen, The Netherlands
*Correspondence to: M.A.M. van Steensel, M.D., Dept. of Hu-man Genetics, Clinical Genetics Section, Radboud UniversityHospital Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Neth-erlands. E-mail: [email protected]
Received 26 February 1997; Accepted 24 April 1998
American Journal of Medical Genetics 80:435 (1998)
© 1998 Wiley-Liss, Inc.