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A novel PORCN mutation in focal dermal hypoplasia
P2018
P2020
The gray zone Rachel Epstein, DO, Largo Medical Center, Largo, FL, United States
Pseudoxanthoma elasticum Jose Aneiros-Fernandez, MD, San Cecilio Clinical Hospital, Department of Pathology, Granada, Spain; Agustin Buendıa Eisman, PhD, San Cecilio Clinical Hospital, Department of Dermatology, Granada, Spain; Francisco O’Valle, PhD, San Cecilio Clinical Hospital, Department of Pathology, Granada, Spain; Husein Husein-ElAhmed, MD, San Cecilio Clinical Hospital, Department of Dermatology, Granada, Spain; Salvador Arias-Santiago, MD, San Cecilio Clinical Hospital, Department of Dermatology, Granada, Spain Background: Pseudoxanthoma elasticum is an inherited disorder of connective tissue in which the elastic fibers in the skin, eyes, and cardiovascular system gradually become calcified and inelastic. This affectation is also known by the name of elastorrhexis widespread or systemic Gr€ onblandeStrandberg syndrome or syndrome Darier-Gr€ onbland-Strandberg (the latter is applied when there is eye involvement).
Griscelli syndrome (GS) is an autosomal recessive disease characterized by graysilver hair and partial pigmentary dilution of the skin. Fewer than 10 cases have been reported in the United States. Currently, Griscelli syndrome is classified into three subtypes based on genetic and molecular features. We present a rare case of an 8year-old male of Middle Eastern descent who presents with gray-silver hair and hypopigmented macules. In addition, we present the differential diagnosis of a patient who presents with gray-silver hair. Commercial support: None identified.
Case report: An 18-year-old woman presented in a neck injury reticulated appearance, consisting of multiple yellowish papules. In the family history has a sister with the same injury. No personal history of interest. The histopathologic examination showed short, curled, frayed, basophilic elastic fibers in the reticular dermis, particularly in the upper and mid-dermis. The diagnosis is pseudoxanthoma elasticum. Discussion: Pseudoxanthoma elasticum is expressed by mutation of the ABCC6 gene located on chromosome 16q13.1, primarily in the liver and kidney. This mutation affects the transport of anionic peptides, allowing the accumulation of metabolites, leading to progressive calcification of elastic fibers. This disease is divided into four types: two autosomal dominant and two autosomal recessive. They are located in areas of flexion (neck, armpits, inguinal folds and periumbilical area), affecting women, with a mean age of 30 years. The clinical findings are angioid streaks in the fundus, optic nerve drusen in the macula, and injury with the appearance of ‘‘orange peel.’’ Commercial support: None identified.
P2019 A novel PORCN mutation in focal dermal hypoplasia Amy Chen, MD, Wright State University Boonshoft School of Medicine, Department of Dermatology, Dayton, OH, United States; David Carr, MD, Wright State University Boonshoft School of Medicine, Department of Dermatology, Dayton, OH, United States; Julian Trevino, MD, Wright State University Boonshoft School of Medicine, Department of Dermatology, Dayton, OH, United States Focal dermal hypoplasia (FDH; OMIM 305600), also known as Goltz or GoltzeGorlin syndrome is a rare X-linked dominant ectomesodermal dysplasia syndrome. Ninety percent of affected individuals are female and the majority of affected males die in utero. PORCN gene, a homologue of the Drosophila melanogaster porcupine gene, was identified as the molecular basis of FDH in 2007. There are 63 different mutations and 10 microdeletions of PORCN identified in FDH so far. There is no correlation between location of the mutation and phenotypic variability. Some clinical variability can be explained by X chromosome inactivation and postzygotic mosaicism. We present a case of FDH with a novel PORCN mutation. A full-term newborn white female presented for evaluation of multiple linear atrophic plaques. No complications were associated with the pregnancy or delivery except for diet controlled gestational diabetes. The parents denied similar physical findings on themselves and three older children. Parents are not consanguineous. Physical examination revealed linear, pink, and atrophic plaques over the right posterior leg, left abdomen, and right elbow. There was complete syndactyly of the third and fourth digits of the right hand, incomplete syndactyly of the second and third digits of the right foot, and polydactyly of the left foot. A notched deformity of the right nasal ala was noted. There was loss of helical fold of the left ear. Other than excessive tearing from bilateral eyes, the ocular examination was within normal limits. The oral examination was unremarkable. FDH was clinically suspected. PORCN mutational analysis of the proband showed a previously unreported c.556-1 G[C single nucleotide change in the intron 5 splice acceptor site. PORCN encodes a putative O-acyltransferase enzyme which enables the transfer of palmitoleic acid to Wnt protein in the endoplasmic reticulum, facilitating Wnt protein secretion and subsequent membrane signaling in embryonic tissue development. There are 19 different Wnt proteins. It is not yet clear which Wnt proteins are substrates for the acyltransferase encoded by PROCN. All PORCN mutations reported thus far are scattered throughout the entire protein, but a hot region located between amino acids 349 and 365 has been noted. Because c556 encodes a splice acceptor site, a mutation could disrupt normal splicing resulting a defective protein. Our patient was treated supportively and her parents received genetic counseling. Commercial support: None identified.
AB88
J AM ACAD DERMATOL
P2021 Case report: GAPO syndrome Lien Kim Thi Ha, DDS, National Hospital of Odonto Stomatology, Ho Chi Minh, Vietnam; An Le Pham, MD, PhD, University of Medicine and Pharmacy of Ho Chi Minh City, Vietnam, Ho Chi Minh, Vietnam; Minh Van Hoang, MD, University of Medicine and Pharmacy of Ho Chi Minh City, Vietnam, Ho Chi Minh, Vietnam; Phuong Hoai Lam, MD, PhD, National Hospital of Odonto Stomatology, Ho Chi Minh, Vietnam GAPO syndrome is a very rare disorder characterized by evident growth retardation, alopecia, pseudoanodontia, and optic atrophy. Up to 2010, only 37 cases have been reported in the medical literature. We report a 12-year-old boy of nonconsanguineous parents with GAPO syndrome, except optic atrophy. Mucocutaneous characteristics were universal alopecia, skin redundance, thick eyelid, scalp cafeau-lait macules, and pseudoanodontia. His features are short stature, craniofacial dysmorphia, osteomalacia, depressed nasal bridge, and prominent dilated scalp vein. His mental and motor functional activities were very good. In addition, he got an orchicrypt and temporary bilateral facial nerve paralysis. However, there have been a characteristic that not mentioned in previous papers as low male hormone (testosterone \2.00 ng/dL). The histopathologic pattern of the scalp skin described the epidermis had an atrophic malpighian layer, the epidermal ridges did not descend in the dermis, and there was a dense proliferation of connective tissue admixed with infiltration of chronic inflammatory cell. This is the first case of GAPO syndrome associated with low male hormone. Commercial support: None identified.
FEBRUARY 2011
P2020
The gray zone Rachel Epstein, DO, Largo Medical Center, Largo, FL, United States
Pseudoxanthoma elasticum Jose Aneiros-Fernandez, MD, San Cecilio Clinical Hospital, Department of Pathology, Granada, Spain; Agustin Buendıa Eisman, PhD, San Cecilio Clinical Hospital, Department of Dermatology, Granada, Spain; Francisco O’Valle, PhD, San Cecilio Clinical Hospital, Department of Pathology, Granada, Spain; Husein Husein-ElAhmed, MD, San Cecilio Clinical Hospital, Department of Dermatology, Granada, Spain; Salvador Arias-Santiago, MD, San Cecilio Clinical Hospital, Department of Dermatology, Granada, Spain Background: Pseudoxanthoma elasticum is an inherited disorder of connective tissue in which the elastic fibers in the skin, eyes, and cardiovascular system gradually become calcified and inelastic. This affectation is also known by the name of elastorrhexis widespread or systemic Gr€ onblandeStrandberg syndrome or syndrome Darier-Gr€ onbland-Strandberg (the latter is applied when there is eye involvement).
Griscelli syndrome (GS) is an autosomal recessive disease characterized by graysilver hair and partial pigmentary dilution of the skin. Fewer than 10 cases have been reported in the United States. Currently, Griscelli syndrome is classified into three subtypes based on genetic and molecular features. We present a rare case of an 8year-old male of Middle Eastern descent who presents with gray-silver hair and hypopigmented macules. In addition, we present the differential diagnosis of a patient who presents with gray-silver hair. Commercial support: None identified.
Case report: An 18-year-old woman presented in a neck injury reticulated appearance, consisting of multiple yellowish papules. In the family history has a sister with the same injury. No personal history of interest. The histopathologic examination showed short, curled, frayed, basophilic elastic fibers in the reticular dermis, particularly in the upper and mid-dermis. The diagnosis is pseudoxanthoma elasticum. Discussion: Pseudoxanthoma elasticum is expressed by mutation of the ABCC6 gene located on chromosome 16q13.1, primarily in the liver and kidney. This mutation affects the transport of anionic peptides, allowing the accumulation of metabolites, leading to progressive calcification of elastic fibers. This disease is divided into four types: two autosomal dominant and two autosomal recessive. They are located in areas of flexion (neck, armpits, inguinal folds and periumbilical area), affecting women, with a mean age of 30 years. The clinical findings are angioid streaks in the fundus, optic nerve drusen in the macula, and injury with the appearance of ‘‘orange peel.’’ Commercial support: None identified.
P2019 A novel PORCN mutation in focal dermal hypoplasia Amy Chen, MD, Wright State University Boonshoft School of Medicine, Department of Dermatology, Dayton, OH, United States; David Carr, MD, Wright State University Boonshoft School of Medicine, Department of Dermatology, Dayton, OH, United States; Julian Trevino, MD, Wright State University Boonshoft School of Medicine, Department of Dermatology, Dayton, OH, United States Focal dermal hypoplasia (FDH; OMIM 305600), also known as Goltz or GoltzeGorlin syndrome is a rare X-linked dominant ectomesodermal dysplasia syndrome. Ninety percent of affected individuals are female and the majority of affected males die in utero. PORCN gene, a homologue of the Drosophila melanogaster porcupine gene, was identified as the molecular basis of FDH in 2007. There are 63 different mutations and 10 microdeletions of PORCN identified in FDH so far. There is no correlation between location of the mutation and phenotypic variability. Some clinical variability can be explained by X chromosome inactivation and postzygotic mosaicism. We present a case of FDH with a novel PORCN mutation. A full-term newborn white female presented for evaluation of multiple linear atrophic plaques. No complications were associated with the pregnancy or delivery except for diet controlled gestational diabetes. The parents denied similar physical findings on themselves and three older children. Parents are not consanguineous. Physical examination revealed linear, pink, and atrophic plaques over the right posterior leg, left abdomen, and right elbow. There was complete syndactyly of the third and fourth digits of the right hand, incomplete syndactyly of the second and third digits of the right foot, and polydactyly of the left foot. A notched deformity of the right nasal ala was noted. There was loss of helical fold of the left ear. Other than excessive tearing from bilateral eyes, the ocular examination was within normal limits. The oral examination was unremarkable. FDH was clinically suspected. PORCN mutational analysis of the proband showed a previously unreported c.556-1 G[C single nucleotide change in the intron 5 splice acceptor site. PORCN encodes a putative O-acyltransferase enzyme which enables the transfer of palmitoleic acid to Wnt protein in the endoplasmic reticulum, facilitating Wnt protein secretion and subsequent membrane signaling in embryonic tissue development. There are 19 different Wnt proteins. It is not yet clear which Wnt proteins are substrates for the acyltransferase encoded by PROCN. All PORCN mutations reported thus far are scattered throughout the entire protein, but a hot region located between amino acids 349 and 365 has been noted. Because c556 encodes a splice acceptor site, a mutation could disrupt normal splicing resulting a defective protein. Our patient was treated supportively and her parents received genetic counseling. Commercial support: None identified.
AB88
J AM ACAD DERMATOL
P2021 Case report: GAPO syndrome Lien Kim Thi Ha, DDS, National Hospital of Odonto Stomatology, Ho Chi Minh, Vietnam; An Le Pham, MD, PhD, University of Medicine and Pharmacy of Ho Chi Minh City, Vietnam, Ho Chi Minh, Vietnam; Minh Van Hoang, MD, University of Medicine and Pharmacy of Ho Chi Minh City, Vietnam, Ho Chi Minh, Vietnam; Phuong Hoai Lam, MD, PhD, National Hospital of Odonto Stomatology, Ho Chi Minh, Vietnam GAPO syndrome is a very rare disorder characterized by evident growth retardation, alopecia, pseudoanodontia, and optic atrophy. Up to 2010, only 37 cases have been reported in the medical literature. We report a 12-year-old boy of nonconsanguineous parents with GAPO syndrome, except optic atrophy. Mucocutaneous characteristics were universal alopecia, skin redundance, thick eyelid, scalp cafeau-lait macules, and pseudoanodontia. His features are short stature, craniofacial dysmorphia, osteomalacia, depressed nasal bridge, and prominent dilated scalp vein. His mental and motor functional activities were very good. In addition, he got an orchicrypt and temporary bilateral facial nerve paralysis. However, there have been a characteristic that not mentioned in previous papers as low male hormone (testosterone \2.00 ng/dL). The histopathologic pattern of the scalp skin described the epidermis had an atrophic malpighian layer, the epidermal ridges did not descend in the dermis, and there was a dense proliferation of connective tissue admixed with infiltration of chronic inflammatory cell. This is the first case of GAPO syndrome associated with low male hormone. Commercial support: None identified.
FEBRUARY 2011