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THE PHYLLOID HYPOMELANOSIS is a defined as a distinct syndrome consisting of achromic phylloid skin lesions in combination with extracutaneous anomalies such as mental retardation , agenesis of corpus callosum , conductive hearing loss ,coloboma and various skeletal defects[1].

Mosaicism in human skin results in different cutaneous patterns: the narrow lines of Blaschko (type 1a), the broad lines of Blaschko (type 1b), the checkerboard pattern (type 2), the phylloid pattern (type 3), and a patchy pattern without midline separation (type 4) (Happle, 1993). The phylloid pattern is characterized by an arrangement of pigmentary disturbances reminiscent of floral ornamentsor a Jugendstil painting (Happle, 1993). Phylloid hypomelanosis is characterized by congenital hypopigmented macules following the phylloid pattern. This article is protected by copyright. All rights reserved.

Trisomy 13, or Patau syndrome, is a chromosomal disorder that can occur in complete, partial, or mosaic forms. Mosaicism is observed in 6% of individuals with trisomy 13 and, in contrast to the complete form, has wide phenotypic variability, longer survival, and in some patients an unusual skin pigmentary pattern similar to phylloid hypomelanosis. We describe here a 12-year-old girl with trisomy 13 mosaicism (mos 47,XX,+13[9]/46,XX[16]) who had three major malformations, an unusual skin pigmentary pattern, and prolonged survival.

We present a case of an otherwise healthy infant with a localized patch of phylloid hypopigmentation bordered by terminal hairs on the back. We believe that this is a unique clinical entity and propose the term "phylloid terminal hair nevus." We believe that this is a localized form of phylloid hypomelanosis that is not associated with extracutaneous abnormalities.

The mosaic pattern of phylloid hypomelanosis is mostly associated with chromosome 13 abnormalities. Recently, 1 case of hypermelanosis in a phylloid pattern has been described. We describe a 29-year-old Japanese male with mental retardation, phylloid hypermelanosis and histopathologically and ultrastructurally peculiar melanocytic nevi, which were associated with 3 aberrant chromosome 13 cell lines. The karyotyping of 30 peripheral blood lymphocytes showed 46,XY,r(13)(p11.2q34) in 21 cells, 45,XY,–13 in 7 cells and 46,XY,dic r(13)(p11.2q34) in 2 cells. Immunohistochemical staining with HMB45 showed a positive reaction to basal keratinocytes in phylloid hypermelanosis. HMB45 staining reacted to the nevus cells and keratinocytes in the melanocytic nevi. Electron microscopy of a specimen excised from a melanocytic nevus showed an unusual finding of aggregated and disfigured melanosomes in the keratinocytes. This case suggests that chromosome 13 abnormalities may be related to the development of phylloid hypermelanosis and the bizarre melanosomes in the keratinocytes of melanocytic nevi.

Various forms of pigmentary dysplasias have been known to be associated with chromosomal mosaicism. One of these disorders, known as phylloid hypomelanosis, has been found to be predominantly associated with abnormalities in chromosome 13. Most of the reported literature involves mosaic trisomy 13 with clinical evidence of abnormal pigmentation in the form of leaf-like or oblong achromic macules following Blaschko's lines. Here, we report on an 8-year-old girl with phylloid hypomelanosis and precocious puberty who was found to have mosaicism for tetrasomy 13q in the form of inverted dup(13)(q21) on her skin fibroblasts as well as peripheral blood karyotype. A higher resolution (244K) chromosomal microarray was done on DNA from skin fibroblasts confirming the breakpoint and gain of distal 13q, which made her tetrasomic for 13q21-qter. This is the first-ever reported association of tetrasomy 13q with phylloid hypomelanosis and precocious puberty. Our report further emphasizes the need to exclude any type of abnormalities of chromosome 13 in patients with phylloid hypopigmentation.

Phylloid hypermelanosis is a less clearly defined pigmentary disturbance than its hypopigmented counterpart, phylloid hypomelanosis. We report the case of a 32-month-old boy who had multiple melanotic macules arranged in a typical phylloid pattern since birth. He also had an abnormal facial appearance, with macrocephaly, frontal bossing, hypertelorism, internal strabismus, and auricular deformities. Psychomotor delay, multiple cystic brain lesions, and bilateral sensorineural hearing loss were also found. A review of associated anomalies as described in this and five previously reported patients with phylloid hypermelanosis shows some vague and inconsistent similarities, such as unusual facial appearance, malformed ears, hearing loss, and mental deficiency, but it is likely that phylloid hypermelanosis represents a class of heterogeneous phenotypes. Future clinical and genetic research may show how many distinct entities can be placed in this group of disorders.

The concept of cutaneous mosaicism has today been proven at the cellular level in at least fifteen different skin disorders. We can distinguish five different patterns of mosaicism, including the phylloid pattern and the lateralization pattern. Etiologically, cutaneous mosaics can be divided into two large categories, epigenetic mosaicism and genomic mosaicism. All forms of epigenetic mosaicism known so far, including the various patterns of X-inactivation, appear to be caused by the action of retrotransposons. A new concept is functional autosomal mosaicism transmittable through the action of retrotransposons, which has been described in mice and dogs and may explain, for example, the familial occurrence of pigmentary mosaicism along the Blaschko lines in human skin. Among the examples of mosaicism of autosomal lethal mutations, phylloid hypomelanosis is a recently recognized neurocutaneous entity caused by mosaic trisomy 13. Possible examples of a type 2 segmental manifestation now include at least fifteen different autosomally dominant skin disorders. This phenomenon is most frequently found in glomangiomatosis, cutaneous leiomyomatosis, and disseminated superficial actinic porokeratosis. Recently proposed examples of didymosis (twin spotting) include cutis tricolor, paired patches of excessive or absent involvement in Darier disease, and didymosis aplasticosebacea characterized by coexistent aplasia cutis congenita and nevus sebaceus. To the list of possible examples of paradominant inheritance, cutis marmorata telangiectatica congenita and speckled lentiginous nevus syndrome have now been added. Revertant mosaicism giving rise to unaffected skin areas in autosomally recessive cutaneous traits will certainly likewise be recognized more often when clinicians are bearing this concept in mind. Such cases can be taken as examples of "natural gene therapy".

In this issue, Oiso et al. [1] present an unusual case of pigmentary mosaicism. A 29-year-old man with mental deficiency had hypermelanotic macules arranged in a phylloid pattern. Cytogenetic analysis of peripheral blood lymphocytes showed 3 different aberrant cell types containing either a monocentric or a dicentric ring chromosome 13, or monosomy 13. Remarkably, no normal karyotype could be found in the 30 cells examined. Although the authors did not analyze fibroblasts derived from skin lesions, it is obvious that the phylloid hypermelanosis of this patient reflects cutaneous mosaicism. The cytogenetic findings documented by Oiso et al. [1] are particularly interesting because aberrations involving chromosome 13 have so far not been described in phylloid hyper melanosis, but only in its counterpart, phylloid hypo melanosis, a disorder that can today be taken as a well-established entity reflecting mosaic trisomy 13 [2– 4] . In fact, most cases of phylloid hypomelanosis are caused by mosaic trisomy 13q [2, 5, 6] . Oiso et al. [1] discuss a previous report on phylloid hypermelanosis [7] . Here, I should like to review 2 additional case reports and, at the same time, explain how the story of the phylloid pattern began. Published online: January 26, 2010

Phylloid hypomelanosis is a distinct type of pigmentary mosaicism characterized by congenital hypochromic macules resembling a floral ornament with various elements such as round or oval patches, asymmetrical macules similar to begonia leaves, or oblong lesions. It has been found to be predominantly associated with abnormalities in chromosome 13 and sometimes as-sociated with different extracutaneous abnormalities. Here, we report 2 new cases of phylloid hypomelanosis due to mosaicism involving chromosome 13. The first one is a mosaicism for a supernumerary marker belonging to chromosome 13 and the second one is the first report of phylloid hypomelanosis associated with a mosaic deletion of 13q. Because of the extremely low level of mosaicism in these 2 cases, SNP array analysis on skin fibroblasts was carried out, showing a 13q21.33-q34 duplication (71,024,411-115,103,529) and a 13q13.3-q34 (38,368,012-115,103,529) deletion. Both cases underline on the one hand the strict connection between phylloid hypomelanosis and anomalies of chromosome 13, and on the other hand the relevance of the SNP array analysis on skin fibroblasts in the detection of low-level mosaicism.

Phylloid hypermelanosis is a rare form of pigmentary mosaicism that has been reported only a few times in the literature (1–6). While phylloid hypomelanosis is linked to trisomy 13, the cause of phylloid hypermelanosis is more obscure (5, 7–13). We describe here a case of phyl-loid hypermelanosis associated with mild developmental delay, cicatricial alopecia, hearing loss and polythelia. CASE REPORT

Counseling parents of a fetus with trisomy 13 mosaicism remains difficult because of the phenotypic variability associated with the condition; some patients exhibit the typical phenotype of complete trisomy 13 with neonatal death, while others have few dysmorphic features and prolonged survival. This article provides a comprehensive review of the prenatal diagnosis and genetic counseling for mosaic trisomy 13, including confined placental mosaicism 13, mosaic trisomy 13 diagnosed at amniocentesis, and phylloid hypomelanosis in association with mosaic trisomy 13.

Background Phylloid hypomelanosis is a rare neurocutaneous syndrome characterized by a pattern of hypopigmentation consisting of leaflike or oblong macules reminiscent of floral ornaments. Associated extracutaneous anomalies include cerebral, ocular, and skeletal defects. Recently it has been suggested that this phenotype originates from mosaic partial or complete trisomy 13. We report clinical and cytogenetic data for 2 cases. Observations A bizarre pattern of multiple leaflike macules was noted in 2 girls with mental deficiency. In patient 1, additional anomalies included syndactyly, clinodactyly, trichomegaly of the eyelashes, low frontal hairline, and several pale pink telangiectatic macules. In patient 2, epileptic seizures, dental malposition, oligodontia, preauricular fistulas, scoliosis, tethered cord, and syringomyelia were noted. A diagnosis of phylloid hypomelanosis was made in both patients. In both patients, blood lymphocytes showed a normal karyotype 46,XX; however, fibroblasts derived from lesional skin demonstrated tetrasomy of chromosome 13q21-qter in patient 1 and trisomy of 13q22-qter in patient 2. Conclusions These 2 cases lend further support to the concept that phylloid hypomelanosis is a distinct clinicogenetic entity that should no longer be confused with pigmentary mosaicism of the Ito type. From a comparison of our cytogenetic findings with those documented in previous articles, we infer that phylloid hypomelanosis is most likely related to the 13q region.

We report a 12-year-old patient with Patau syndrome, in whom two cell lines were present from birth, one with total trisomy 13 due to isochromosome (13q), and one with partial trisomy 13. A cytogenetic re-evaluation at 9 years of age brought to light in skin fibroblasts a third cell line, partially monosomic for chromosome 13. The derivatives (13) present in the three cell lines were characterized through fluorescence in situ hybridization (FISH) experiments with suitable probes; the results suggested a sequence of rearrangements which beginning from an isochromosome (13q) could have led to the other two derivatives. We report the clinical data at birth and at the age of 12; at this age pigmentary lesions with phylloid pattern were noted. Cytogenetic findings of the chromosomal analyses on different tissues, including skin fibroblasts from differently pigmented areas, are also reported.

© 2010 The Authors. doi: 10.2340/00015555-0810 Journal Compilation © 2010 Acta Dermato-Venereologica. ISSN 0001-5555 Sir, Congenital naevi of the melanocytic system include numerous types, which differ in their clinical appearance, pattern of distribution, and histopathological features (1). Examples are large congenital melanocytic naevus, macular naevus spilus, papular naevus spilus, cafe-aulait macules of neurofibromatosis 1, cafe-au-lait macules arranged in broad bands as noted in McCune-Albright syndrome, partial unilateral lentiginosis, naevus achromicus (naevus depigmentosus), phylloid hypermelanosis, and phylloid hypomelanosis (1–3). We describe here two patients with a systematized pigmentary naevus that differed from all naevi reported so far.

In most patients with hypomelanosis of Ito, the hypopigmentation is characterized by narrow bands following the lines of Blaschko. We report a 13-year-old severely retarded girl with leaf-shaped patches of hypopigmentation on the back together with short stature, scoliosis, facial dysmorphism, and asymmetrical leg length. The cytogenetic examination of both lymphocytes and fibroblasts demonstrated a mosaicism of 46,XX/47,XX+13. This result was confirmed by in situ hybridization using a chromosome 13-specific library in interphase cells. The pigmentary disturbance of our patient was similar to the phylloid pattern (type 3) of the classification of pigmentary patterns postulated by Happle. This type has been described in four patients so far, along with additional anomalies and a chromosomal mosaisicm in two patients.

This 18 month old boy presented with a history of hypopigmented macular lesions, mild neurodevelopmental delay and recurrent episodes of acrocyanosis with tachycardia and increased tone. The cutaneous lesions developed from the age of 3 months, affecting the right trunk and right upper and lower limbs. Examination revealed large well-defined hypopigmented macules in a classical phylloid pattern, with a midline cut-off anteriorly and posteriorly on the trunk, compatible with a diagnosis of phylloid hypomelanosis. Mild facial dysmorphism was noted. Neurodevelopmental assessment at the age of 12 months suggested mild global delay; EEG and MRI of the CNS are pending. Cardiovascular examination was normal, however 24 hour ECG revealed non-specific ST segment changes. Ophthalmologic assessment was normal. Array comparative genomic hybridisation on a peripheral blood sample was normal. Karyotyping of affected and unaffected skin fibroblasts is underway. Phylloid hypomelanosis (Greek phyllon = leaf, eidos = form) is characterised by congenital hypopigmented macules resembling a floral ornament, with round, oval or oblong patches (1), distinct from the commoner Blashko-linear distribution. It is a rare but highly specific sign of chromosomal mosaicism, universally associated thus far in the literature with mosaicism for duplications of 13q (1.2). Associated extracutaneous anomalies vary, and can include neurological, ocular, dental and skeletal defects (2). Cardiovascular abnormalities have not been reported thus far, and follow-up in our patient will clarify whether this is an associated or incidental feature. Affected individuals require multi-disciplinary assessment and long-term follow-up. As this is a somatic mosaic condition the possibility of fully affected offspring from the probands should be addressed at an appropriate age. References Phylloid hypomelanosis is closely related to mosaic trisomy 13. Happle R. Eur J Dermatol. 2000 Oct-Nov; 10(7):511–2. Phylloid hypomelanosis and mosaic partial trisomy 13: two cases that provide further evidence of a distinct clinicogenetic entity. Gonzalez-Ensenat MA, Vicente A, Poo P, Catala V, Mar Perez-Iribarne M, Fuster C, Gean E, Happle R. Arch Dermatol. 2009 May; 145(5):576–8.

Background: The skin is especially suitable for the study of mosaicism. In this review, the various genetic mechanisms leading to mosaicism and the resulting cutaneous patterns are considered. Observations: Mosaicism may produce different cutaneous patterns such as the lines of Blaschko, the checkerboard pattern, the phylloid pattern, and a patchy pattern without midline separation. A unique lateralization pattern is observed in the CHILD syndrome. Two major genetic categories are functional mosaics resulting from X inactivation and genomic mosaics caused by autosomal mutations. Functional mosaicism may be caused by either male-lethal or nonlethal X-linked mutations. Similarly, autosomal mutations resulting in genomic mosaicism may be either lethal or nonlethal. Many mosaics are caused by loss of heterozygosity, and uncommonly this mechanism may give rise to twin spots such as vascular twin nevi. Some cutaneous mosaic phenotypes virtually always occur sporadically, but exceptionally may show a familial aggregation. This paradox may be explained by paradominant inheritance. Heterozygous individuals are, as a rule, unaffected, but they express the birthmark when allelic loss occurs during embryogenesis. Conclusions: The concept of cutaneous mosaicism is important for gene mapping because here we have the opportunity to study two populations of cells differing only with regard to the mutation causing mosaicism. Future research will probably show that a specific genetic anomaly, when present as a mosaic, always produces the same type of cutaneous pattern. ( Arch Dermatol. 1993;129:1460-1470)