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An Infant With Atrophic and Wrinkled Abdominal Skin

An Infant With Atrophic and Wrinkled Abdominal Skin Case A 7-week-old white male infant born at 37 weeks’ gestation via cesarean delivery owing to maternal hypertension presented to our dermatology clinic for evaluation of white patches and plaques on his abdomen and thighs. The patient’s weight, height, and head circumference were in the 25th to 75th percentiles. Examination revealed hypopigmented atrophic papules and plaques on the lower abdomen and proximal thighs suggestive of sclerodermatous changes. The surrounding skin appeared wrinkled (Figure 1, A). The patient was also noted to have a triangular face, pointed nose, and micrognathia. Figure 1. View LargeDownload A, The patient’s abdomen; B and C, micrographs (hematoxylin-eosin, original magnification ×4, and elastin, original magnification ×20, respectively). Two punch biopsy specimens were taken (Figure 1, A and B). What is your diagnosis? Read the Discussion. Discussion Diagnosis Hutchinson–Gilford progeria syndrome (HGPS) Microscopic Findings and Clinical Course The biopsy specimens demonstrated fibrosis in the papillary dermis and a patchy lymphohistiocytic inflammatory infiltrate. There were thickened collagen bundles with adipocytes situated superficially around the collagen bundles (Figure 1, B). An elastin stain on the specimen showed a diminution of elastic fibers (Figure 1, C). These findings were consistent with sclerodermatous changes. Over the next few months, our patient exhibited other characteristic features of HGPS, including prominent scalp veins, midface hypoplasia, circumoral cyanosis, absent earlobes, and frontal bossing (Figure 2). Genetic testing was performed, and DNA analysis revealed a c.1824C>T mutation in exon 11 of the LMNA gene, confirming the diagnosis of HGPS. Figure 2. View LargeDownload A photograph of the patient. HGPS is a rare premature aging disorder first described in 1886 by Sir Jonathan Hutchinson. The incidence is 1 in 4 to 8 million, most patients being white. The male-to-female ratio is 1.5:1. Patients usually appear normal at birth and then exhibit a characteristic clinical phenotype in the first few years of life. Although children with HGPS develop many attributes of aging, including skin atrophy, osteoporosis, alopecia, arthritis, and loss of subcutaneous fat, other signs of aging, such as cataracts and dementia, do not occur. Accelerated atherosclerosis leads to cerebrovascular accidents, myocardial infarctions, and congestive heart failure in the second decade of life.1 Distinctive dermatologic changes are often the first manifestation and can be critical in establishing the diagnosis. Findings can include sclerodermatous skin changes of the trunk and thighs, circumoral cyanosis, alopecia, nail hypoplasia or dystrophy, easy bruising, decreased sweating secondary to decreased eccrine glands, and prominent scalp veins. Characteristic facial features include midface hypoplasia, micrognathia, prominent eyes, beaklike nose, and absent earlobes. Over the first year, skin becomes thin, tight, and shiny in some areas and loose and wrinkled in others. Irregular hyperpigmentation is often present. The alopecia is characterized by total scalp, eyebrow, and eyelash hair loss with replacement by thin vellus hairs on the scalp. Other features include delayed dentition and high-pitched voice.2-7 Genetic testing can confirm the diagnosis. HGPS is caused by accumulation of a farnesylated form of prelamin A termed progerin. The accumulation results from aberrant processing caused by sporadic autosomal dominant mutations in the LMNA gene located on chromosome 1. Autosomal recessive forms have also been reported.2 When this protein is farnesylated, it is toxic to cells, leading patients to display the phenotype associated with HGPS.8 Trials with farnesyltransferase inhibitors are under way, but treatment remains supportive.9 Back to top Article Information Corresponding Author: Ilene Rothman, MD, Department of Dermatology, State University of New York at Buffalo, Women and Children’s Hospital of Buffalo, 219 Bryant St, Buffalo, NY 14222 (irothman@kaleidahealth.org). Published Online: December 4, 2013. doi:10.1001/jamadermatol.2013.5721. Conflict of Interest Disclosures: None reported. Section Editor: Mary S. Stone, MD; Assistant Section Editors: Soon Bahrami, MD; Carrie Ann R. Cusack, MD; Molly A. Hinshaw, MD; Arni K. Kristjansson, MD; Lori D. Prok, MD. References 1. Badame AJ. Progeria. Arch Dermatol. 1989;125(4):540-544.PubMedGoogle ScholarCrossref 2. Mazereeuw-Hautier J, Wilson LC, Mohammed S, et al. Hutchinson-Gilford progeria syndrome: clinical findings in three patients carrying the G608G mutation in LMNA and review of the literature. Br J Dermatol. 2007;156(6):1308-1314.PubMedGoogle ScholarCrossref 3. Moynahan EJ. Progeria (Hastings Gilford) presenting as scleroderma in early infancy. Proc R Soc Med. 1962;55(3):240.PubMedGoogle Scholar 4. Feingold M, Kidd R. Progeria and scleroderma in infancy. Am J Dis Child. 1971;122(1):61-62.PubMedGoogle Scholar 5. Jansen T, Romiti R. Progeria infantum (Hutchinson-Gilford syndrome) associated with scleroderma-like lesions and acro-osteolysis: a case report and brief review of the literature. Pediatr Dermatol. 2000;17(4):282-285.PubMedGoogle ScholarCrossref 6. Gillar PJ, Kaye CI, McCourt JW. Progressive early dermatologic changes in Hutchinson-Gilford progeria syndrome. Pediatr Dermatol. 1991;8(3):199-206.PubMedGoogle ScholarCrossref 7. Madej-Pilarczyk A, Rosińska-Borkowska D, Rekawek J, et al. Progeroid syndrome with scleroderma-like skin changes associated with homozygous R435C LMNA mutation. Am J Med Genet A. 2009;149A(11):2387-2392.PubMedGoogle ScholarCrossref 8. Merideth MA, Gordon LB, Clauss S, et al. Phenotype and course of Hutchinson-Gilford progeria syndrome. N Engl J Med. 2008;358(6):592-604.PubMedGoogle ScholarCrossref 9. Meta M, Yang SH, Bergo MO, Fong LG, Young SG. Protein farnesyltransferase inhibitors and progeria. Trends Mol Med. 2006;12(10):480-487.PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Dermatology American Medical Association

An Infant With Atrophic and Wrinkled Abdominal Skin

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References (10)

Publisher
American Medical Association
Copyright
Copyright © 2014 American Medical Association. All Rights Reserved.
ISSN
2168-6068
eISSN
2168-6084
DOI
10.1001/jamadermatol.2013.5721
pmid
24305757
Publisher site
See Article on Publisher Site

Abstract

Case A 7-week-old white male infant born at 37 weeks’ gestation via cesarean delivery owing to maternal hypertension presented to our dermatology clinic for evaluation of white patches and plaques on his abdomen and thighs. The patient’s weight, height, and head circumference were in the 25th to 75th percentiles. Examination revealed hypopigmented atrophic papules and plaques on the lower abdomen and proximal thighs suggestive of sclerodermatous changes. The surrounding skin appeared wrinkled (Figure 1, A). The patient was also noted to have a triangular face, pointed nose, and micrognathia. Figure 1. View LargeDownload A, The patient’s abdomen; B and C, micrographs (hematoxylin-eosin, original magnification ×4, and elastin, original magnification ×20, respectively). Two punch biopsy specimens were taken (Figure 1, A and B). What is your diagnosis? Read the Discussion. Discussion Diagnosis Hutchinson–Gilford progeria syndrome (HGPS) Microscopic Findings and Clinical Course The biopsy specimens demonstrated fibrosis in the papillary dermis and a patchy lymphohistiocytic inflammatory infiltrate. There were thickened collagen bundles with adipocytes situated superficially around the collagen bundles (Figure 1, B). An elastin stain on the specimen showed a diminution of elastic fibers (Figure 1, C). These findings were consistent with sclerodermatous changes. Over the next few months, our patient exhibited other characteristic features of HGPS, including prominent scalp veins, midface hypoplasia, circumoral cyanosis, absent earlobes, and frontal bossing (Figure 2). Genetic testing was performed, and DNA analysis revealed a c.1824C>T mutation in exon 11 of the LMNA gene, confirming the diagnosis of HGPS. Figure 2. View LargeDownload A photograph of the patient. HGPS is a rare premature aging disorder first described in 1886 by Sir Jonathan Hutchinson. The incidence is 1 in 4 to 8 million, most patients being white. The male-to-female ratio is 1.5:1. Patients usually appear normal at birth and then exhibit a characteristic clinical phenotype in the first few years of life. Although children with HGPS develop many attributes of aging, including skin atrophy, osteoporosis, alopecia, arthritis, and loss of subcutaneous fat, other signs of aging, such as cataracts and dementia, do not occur. Accelerated atherosclerosis leads to cerebrovascular accidents, myocardial infarctions, and congestive heart failure in the second decade of life.1 Distinctive dermatologic changes are often the first manifestation and can be critical in establishing the diagnosis. Findings can include sclerodermatous skin changes of the trunk and thighs, circumoral cyanosis, alopecia, nail hypoplasia or dystrophy, easy bruising, decreased sweating secondary to decreased eccrine glands, and prominent scalp veins. Characteristic facial features include midface hypoplasia, micrognathia, prominent eyes, beaklike nose, and absent earlobes. Over the first year, skin becomes thin, tight, and shiny in some areas and loose and wrinkled in others. Irregular hyperpigmentation is often present. The alopecia is characterized by total scalp, eyebrow, and eyelash hair loss with replacement by thin vellus hairs on the scalp. Other features include delayed dentition and high-pitched voice.2-7 Genetic testing can confirm the diagnosis. HGPS is caused by accumulation of a farnesylated form of prelamin A termed progerin. The accumulation results from aberrant processing caused by sporadic autosomal dominant mutations in the LMNA gene located on chromosome 1. Autosomal recessive forms have also been reported.2 When this protein is farnesylated, it is toxic to cells, leading patients to display the phenotype associated with HGPS.8 Trials with farnesyltransferase inhibitors are under way, but treatment remains supportive.9 Back to top Article Information Corresponding Author: Ilene Rothman, MD, Department of Dermatology, State University of New York at Buffalo, Women and Children’s Hospital of Buffalo, 219 Bryant St, Buffalo, NY 14222 (irothman@kaleidahealth.org). Published Online: December 4, 2013. doi:10.1001/jamadermatol.2013.5721. Conflict of Interest Disclosures: None reported. Section Editor: Mary S. Stone, MD; Assistant Section Editors: Soon Bahrami, MD; Carrie Ann R. Cusack, MD; Molly A. Hinshaw, MD; Arni K. Kristjansson, MD; Lori D. Prok, MD. References 1. Badame AJ. Progeria. Arch Dermatol. 1989;125(4):540-544.PubMedGoogle ScholarCrossref 2. Mazereeuw-Hautier J, Wilson LC, Mohammed S, et al. Hutchinson-Gilford progeria syndrome: clinical findings in three patients carrying the G608G mutation in LMNA and review of the literature. Br J Dermatol. 2007;156(6):1308-1314.PubMedGoogle ScholarCrossref 3. Moynahan EJ. Progeria (Hastings Gilford) presenting as scleroderma in early infancy. Proc R Soc Med. 1962;55(3):240.PubMedGoogle Scholar 4. Feingold M, Kidd R. Progeria and scleroderma in infancy. Am J Dis Child. 1971;122(1):61-62.PubMedGoogle Scholar 5. Jansen T, Romiti R. Progeria infantum (Hutchinson-Gilford syndrome) associated with scleroderma-like lesions and acro-osteolysis: a case report and brief review of the literature. Pediatr Dermatol. 2000;17(4):282-285.PubMedGoogle ScholarCrossref 6. Gillar PJ, Kaye CI, McCourt JW. Progressive early dermatologic changes in Hutchinson-Gilford progeria syndrome. Pediatr Dermatol. 1991;8(3):199-206.PubMedGoogle ScholarCrossref 7. Madej-Pilarczyk A, Rosińska-Borkowska D, Rekawek J, et al. Progeroid syndrome with scleroderma-like skin changes associated with homozygous R435C LMNA mutation. Am J Med Genet A. 2009;149A(11):2387-2392.PubMedGoogle ScholarCrossref 8. Merideth MA, Gordon LB, Clauss S, et al. Phenotype and course of Hutchinson-Gilford progeria syndrome. N Engl J Med. 2008;358(6):592-604.PubMedGoogle ScholarCrossref 9. Meta M, Yang SH, Bergo MO, Fong LG, Young SG. Protein farnesyltransferase inhibitors and progeria. Trends Mol Med. 2006;12(10):480-487.PubMedGoogle ScholarCrossref

Journal

JAMA DermatologyAmerican Medical Association

Published: Feb 1, 2014

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