Pediatric Dermatology Vol. 31 No. 1 e33–e35, 2014
Familial Papular Epidermal Nevus with “Skyline” Basal Cell Layer Abstract: Papular epidermal nevus with “skyline” basal cell layer (PENS), a novel keratinocytic nevus, has recently been described as a mosaic condition with varying presentations. We herein describe typical PENS lesions, which usually occur sporadically, affecting two members of the same family. The concept of paradominant inheritance is proposed to explain the paradox of occasional transmission of normally sporadically occurring traits.
Papular epidermal nevus with “skyline” basal cell layer (PENS) is a newly described keratinocytic nevus occurring in both a randomized pattern and with linear distribution along Blaschko’s lines (1). It appears as single or multiple hyperkeratotic papules with a rough and slightly scaly surface
and variable shape (2) occurring sporadically or in association with neurologic abnormalities, making up PENS syndrome (3). Histopathologic examination shows orthokeratotic hyperkeratosis, acanthosis with broad and rectangular ridges, and a basal layer with a striking palisaded arrangement of basal cell nuclei resembling the peculiar basal cell layer pattern described in Bowen disease (4). Here we describe PENS nevus affecting two members of the same family. CASE REPORTS A 24-year-old woman presented with three asymptomatic cutaneous lesions that had appeared shortly after birth and remained stable over time. The first lesion, on the neck, appeared as an elongated plaque, yellowish in color and with a hyperkeratotic surface (Fig. 1A). The second lesion appeared as an isolated roundish plaque on the left buttock, whitish in color with a shiny surface (Fig. 1B). Several white papules with a rough scaly surface, polycyclic borders, and a tendency to coalescence in one crop were visible on the hypogastric area (Fig. 1C). Her 18-month-old son had a similar cutaneous lesion on the right elbow (Fig. 1D).
B A
C
D
Figure 1. Typical papular epidermal nevus with “skyline” basal cell layer lesions located on the (A) neck, (B) left buttock, and (C) hypogastric area in the mother and (D) on the right arm of her son.
DOI: 10.1111/pde.12251
© 2013 Wiley Periodicals, Inc.
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e34 Pediatric Dermatology Vol. 31 No. 1 January/February 2014
A
B
C
D
Figure 2. Skin biopsy specimens show orthokeratotic hyperkeratosis; acanthosis with broad, rectangular rete ridges; and a “ribbon” of basal keratinocytes with “skyline” pattern in (A–B) a mother and (C–D) son.
Both patients were in good general health, with no extracutaneous anomalies or dysmorphic features reported. Histopathologic examination of both biopsy specimens demonstrated a typical “skyline pattern” (Fig. 2A–D). DISCUSSION All cases of PENS reported in the literature have been sporadic, except for two brothers mentioned by Tadini et al in the description of PENS syndrome (2). In these cases, the boys presented with typical skin lesions, but only the younger sibling had a neurologic disorder, whereas his elder brother was healthy. This occurrence suggests that the mutational event could have affected the germline as a gonadal mosaicism in one of the two unaffected parents, causing transmission of the abnormality to the offspring. We describe PENS nevus also affecting two members of the same family. Happle (5) introduced the concept of paradominant inheritance in 1992 to explain the paradox of the occasional transmission of normally sporadically occurring traits. Individuals who are heterozygous for a paradominant mutation are usually healthy and can transmit the mutation unnoticed over several generations. The trait becomes manifest when an early postzygotic somatic mutation causes a loss of the corresponding wild-type allele
(loss of heterozygosity), resulting in a cell clone that is homozygous or hemizygous for the mutation with a mosaic distribution of affected tissues. A familial aggregation would only be observed when a rare event of postzygotic loss of heterozygosity occurs, during the period of embryogenesis, in several members of a family. In conclusion, we propose that PENS nevus may constitute another example of disease in which paradominant inheritance might explain why it occurs almost always sporadically, with rare cases of familial transmission as reported here. REFERENCES 1. Faure E, Tadini G, Brena M et al. Papular epidermal nevus with “skyline” basal cell layer (PENS) following a Blaschko linear pattern. Pediatr Dermatol 2013 Apr 19. doi: 10.1111/pde.12141 [Epub ahead of print]. 2. Torrelo A, Colmenero I, Kristal L et al. Papular epidermal nevus with “skyline” basal cell layer (PENS). J Am Acad Dermatol 2011;64:888–892. 3. Tadini G, Restano E, Happle R et al. PENS syndrome: a new neurocutaneous phenotype. Dermatology 2012;224:24–30. 4. Saglam O, Salama M, Meier F et al. Immunohistochemical staining of palisading basal cell in Bowen’s disease and basal involvement in actinic keratosis: contrasting staining patterns suggest different cells of origin. Am J Dermatopathol 2008;30:123–126.
Brief Report e35
5. Happle R. Paradominant inheritance: a possible explanation for Becker’s pigmented hairy nevus. Eur J Dermatol 1992;2:39–40. Michela Brena, M.D.* Francesca Besagni, M.D.† Vinicio Boneschi, M.D.* Gianluca Tadini, M.D.*,‡ *Section of Dermatology, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico di Milano, Department of Pathophysiology and Transplantation, University of Milan, Italy, †Section of Dermatology,
Department of Surgical Sciences, Parma University, Parma, Italy, ‡Pediatric Clinic 1, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, Department of Pathophysiology and Transplantation, University of Milan, Italy Address correspondence to Gianluca Tadini, M.D., Section of Dermatology, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico di Milano, Department of Pathophysiology and Transplantation, University of Milan, Via Pace 9, Milan, Italy, or e-mail: [email protected].
Familial Papular Epidermal Nevus with “Skyline” Basal Cell Layer Abstract: Papular epidermal nevus with “skyline” basal cell layer (PENS), a novel keratinocytic nevus, has recently been described as a mosaic condition with varying presentations. We herein describe typical PENS lesions, which usually occur sporadically, affecting two members of the same family. The concept of paradominant inheritance is proposed to explain the paradox of occasional transmission of normally sporadically occurring traits.
Papular epidermal nevus with “skyline” basal cell layer (PENS) is a newly described keratinocytic nevus occurring in both a randomized pattern and with linear distribution along Blaschko’s lines (1). It appears as single or multiple hyperkeratotic papules with a rough and slightly scaly surface
and variable shape (2) occurring sporadically or in association with neurologic abnormalities, making up PENS syndrome (3). Histopathologic examination shows orthokeratotic hyperkeratosis, acanthosis with broad and rectangular ridges, and a basal layer with a striking palisaded arrangement of basal cell nuclei resembling the peculiar basal cell layer pattern described in Bowen disease (4). Here we describe PENS nevus affecting two members of the same family. CASE REPORTS A 24-year-old woman presented with three asymptomatic cutaneous lesions that had appeared shortly after birth and remained stable over time. The first lesion, on the neck, appeared as an elongated plaque, yellowish in color and with a hyperkeratotic surface (Fig. 1A). The second lesion appeared as an isolated roundish plaque on the left buttock, whitish in color with a shiny surface (Fig. 1B). Several white papules with a rough scaly surface, polycyclic borders, and a tendency to coalescence in one crop were visible on the hypogastric area (Fig. 1C). Her 18-month-old son had a similar cutaneous lesion on the right elbow (Fig. 1D).
B A
C
D
Figure 1. Typical papular epidermal nevus with “skyline” basal cell layer lesions located on the (A) neck, (B) left buttock, and (C) hypogastric area in the mother and (D) on the right arm of her son.
DOI: 10.1111/pde.12251
© 2013 Wiley Periodicals, Inc.
e33
e34 Pediatric Dermatology Vol. 31 No. 1 January/February 2014
A
B
C
D
Figure 2. Skin biopsy specimens show orthokeratotic hyperkeratosis; acanthosis with broad, rectangular rete ridges; and a “ribbon” of basal keratinocytes with “skyline” pattern in (A–B) a mother and (C–D) son.
Both patients were in good general health, with no extracutaneous anomalies or dysmorphic features reported. Histopathologic examination of both biopsy specimens demonstrated a typical “skyline pattern” (Fig. 2A–D). DISCUSSION All cases of PENS reported in the literature have been sporadic, except for two brothers mentioned by Tadini et al in the description of PENS syndrome (2). In these cases, the boys presented with typical skin lesions, but only the younger sibling had a neurologic disorder, whereas his elder brother was healthy. This occurrence suggests that the mutational event could have affected the germline as a gonadal mosaicism in one of the two unaffected parents, causing transmission of the abnormality to the offspring. We describe PENS nevus also affecting two members of the same family. Happle (5) introduced the concept of paradominant inheritance in 1992 to explain the paradox of the occasional transmission of normally sporadically occurring traits. Individuals who are heterozygous for a paradominant mutation are usually healthy and can transmit the mutation unnoticed over several generations. The trait becomes manifest when an early postzygotic somatic mutation causes a loss of the corresponding wild-type allele
(loss of heterozygosity), resulting in a cell clone that is homozygous or hemizygous for the mutation with a mosaic distribution of affected tissues. A familial aggregation would only be observed when a rare event of postzygotic loss of heterozygosity occurs, during the period of embryogenesis, in several members of a family. In conclusion, we propose that PENS nevus may constitute another example of disease in which paradominant inheritance might explain why it occurs almost always sporadically, with rare cases of familial transmission as reported here. REFERENCES 1. Faure E, Tadini G, Brena M et al. Papular epidermal nevus with “skyline” basal cell layer (PENS) following a Blaschko linear pattern. Pediatr Dermatol 2013 Apr 19. doi: 10.1111/pde.12141 [Epub ahead of print]. 2. Torrelo A, Colmenero I, Kristal L et al. Papular epidermal nevus with “skyline” basal cell layer (PENS). J Am Acad Dermatol 2011;64:888–892. 3. Tadini G, Restano E, Happle R et al. PENS syndrome: a new neurocutaneous phenotype. Dermatology 2012;224:24–30. 4. Saglam O, Salama M, Meier F et al. Immunohistochemical staining of palisading basal cell in Bowen’s disease and basal involvement in actinic keratosis: contrasting staining patterns suggest different cells of origin. Am J Dermatopathol 2008;30:123–126.
Brief Report e35
5. Happle R. Paradominant inheritance: a possible explanation for Becker’s pigmented hairy nevus. Eur J Dermatol 1992;2:39–40. Michela Brena, M.D.* Francesca Besagni, M.D.† Vinicio Boneschi, M.D.* Gianluca Tadini, M.D.*,‡ *Section of Dermatology, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico di Milano, Department of Pathophysiology and Transplantation, University of Milan, Italy, †Section of Dermatology,
Department of Surgical Sciences, Parma University, Parma, Italy, ‡Pediatric Clinic 1, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, Department of Pathophysiology and Transplantation, University of Milan, Italy Address correspondence to Gianluca Tadini, M.D., Section of Dermatology, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico di Milano, Department of Pathophysiology and Transplantation, University of Milan, Via Pace 9, Milan, Italy, or e-mail: [email protected].
