Leopard syndrome overview: Difference between revisions
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==Overview== | ==Overview== | ||
LEOPARD syndrome is a rare [[autosomal dominant]],<ref>{{cite journal |author=Coppin BD, Temple IK |title=Multiple lentigines syndrome (LEOPARD syndrome or progressive cardiomyopathic lentiginosis) |journal=J. Med. Genet. |volume=34 |issue=7 |pages=582–6 |year=1997 |pmid=9222968 |doi=}}</ref> caused by a [[mutation]] in the [[PTPN11|protein tyrosine phosphatase non-receptor type 11 gene]]. Many systems can be involved, mostly involving the skin, skeletal and cardiovascular systems, but in other cases they are absent. The word LEOPARD is an acronym for the major features of this disorder, including multiple '''L'''entigines, '''E'''KG abnormalities, '''O'''cular hypertelorism, '''P'''ulmonic stenosis, '''A'''bnormal genitalia, '''R'''etardation of growth, and sensorineural '''D'''eafness | |||
==Historical Perspective== | ==Historical Perspective== | ||
It was first described by Zeisler and Becker with multiple [[lentigo|lentigines]], [[hypertelorism]], [[pectus carinatum]] (protruding breastbone) and [[prognathism]] (protrusion of lower jaw) in 1936.<ref name="Zeisler1936">{{cite journal|last1=Zeisler|first1=Erwin P.|title=GENERALIZED LENTIGO<subtitle>ITS RELATION TO SYSTEMIC NONELEVATED NEVI</subtitle>|journal=Archives of Dermatology|volume=33|issue=1|year=1936|pages=109|issn=0003-987X|doi=10.1001/archderm.1936.01470070112010}}</ref> | It was first described by Zeisler and Becker with multiple [[lentigo|lentigines]], [[hypertelorism]], [[pectus carinatum]] (protruding breastbone) and [[prognathism]] (protrusion of lower jaw) in 1936.<ref name="Zeisler1936">{{cite journal|last1=Zeisler|first1=Erwin P.|title=GENERALIZED LENTIGO<subtitle>ITS RELATION TO SYSTEMIC NONELEVATED NEVI</subtitle>|journal=Archives of Dermatology|volume=33|issue=1|year=1936|pages=109|issn=0003-987X|doi=10.1001/archderm.1936.01470070112010}}</ref> | ||
In 1962, cardiac abnormalities and short stature were first associated with the condition.<ref name="Zeisler1936">{{cite journal|last1=Zeisler|first1=Erwin P.|title=GENERALIZED LENTIGO<subtitle>ITS RELATION TO SYSTEMIC NONELEVATED NEVI</subtitle>|journal=Archives of Dermatology|volume=33|issue=1|year=1936|pages=109|issn=0003-987X|doi=10.1001/archderm.1936.01470070112010}}</ref> | In 1962, cardiac abnormalities and short stature were first associated with the condition.<ref name="Zeisler1936">{{cite journal|last1=Zeisler|first1=Erwin P.|title=GENERALIZED LENTIGO<subtitle>ITS RELATION TO SYSTEMIC NONELEVATED NEVI</subtitle>|journal=Archives of Dermatology|volume=33|issue=1|year=1936|pages=109|issn=0003-987X|doi=10.1001/archderm.1936.01470070112010}}</ref> | ||
==Pathophysiology== | ==Pathophysiology== | ||
LEOPARD syndrome is most commonly caused by [[missense mutation]]s in the [[PTPN11]] gene. It has also been associated with other gene mutations such as [[c-Raf|RAF1]] and [[BRAF]]. | |||
== | ==Epidemiology and Demographics== | ||
Leopaed syndrome is a rare condition, but the exact birth prevalence is unknown. Approximately 200 patients have been reported.<ref name="pmid1258892">{{cite journal| author=Voron DA, Hatfield HH, Kalkhoff RK| title=Multiple lentigines syndrome. Case report and review of the literature. | journal=Am J Med | year= 1976 | volume= 60 | issue= 3 | pages= 447-56 | pmid=1258892 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1258892 }} </ref> However, LEOPARD syndrome is likely underdiagnosed or misdiagnosed as many of its features are mild and the correct diagnosis might be missed in the absence of [[lentiginosis]]. | |||
== | ==Natural History, Complications and Prognosis== | ||
In general, males are more affected than females. LEOPARD syndrome is not a life threatening diagnosis, cardiomyopathy and other pathologic findings involving the cardiovascular system may be a cause of death in those whose cardiac deformities are profound. | |||
==History and Symptoms== | |||
LEOPARD syndrome affects many areas in the body. The characteristic feature associated with the condition is brown skin spots called [[lentigines]]. Patients are showing a wide spectrum of features include multiple lentigines, facial dysmorphisms, cardiac anomalies, electrocardiographic (EKG) conduction abnormalities, [[Failure to thrive|retardation of growth]], abnormal genitalia and [[Sensorineural hearing loss|sensorineural deafness]].<ref name="pmid5771505">{{cite journal| author=Gorlin RJ, Anderson RC, Blaw M| title=Multiple lentigenes syndrome. | journal=Am J Dis Child | year= 1969 | volume= 117 | issue= 6 | pages= 652-62 | pmid=5771505 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=5771505 }} </ref> | |||
===Laboratory Findings=== | |||
Hormonal abnormalities may be revealed in some patients with endocrine system involvement. laboratory studies should include molecular analysis of the [[PTPN11]] and [[c-Raf|RAF1]] genes.<ref>{{cite journal |author=Digilio MC, Sarkozy A, de Zorzi A, ''et al'' |title=LEOPARD syndrome: clinical diagnosis in the first year of life |journal=Am. J. Med. Genet. A |volume=140 |issue=7 |pages=740–6 |year=2006 |pmid=16523510 |doi=10.1002/ajmg.a.31156}}</ref> | |||
===Imaging Studies=== | |||
Different imaging studies like [[X-rays]], [[CT scanning]], and [[Echocardiography]] have been used to detect abnormalities of LEOPARD syndrome. | |||
==Medical Therapy== | |||
Medical management depend on the symptoms present. Drug therapy for cardiac abnormalities,endocrine, and dermatological issues is recommended. | |||
==Surgical Therapy== | |||
Different procedures may be necessary in cases with severe outflow tract obstruction<ref name="pmid17697839">{{cite journal| author=Limongelli G, Pacileo G, Marino B, Digilio MC, Sarkozy A, Elliott P et al.| title=Prevalence and clinical significance of cardiovascular abnormalities in patients with the LEOPARD syndrome. | journal=Am J Cardiol | year= 2007 | volume= 100 | issue= 4 | pages= 736-41 | pmid=17697839 | doi=10.1016/j.amjcard.2007.03.093 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17697839 }} </ref>, patients with [[cryptorchidism]], genitourinary, or severe skeletal deformity. | |||
==Primary Prevention== | |||
Genetic counseling should be offered before deciding to have children, careful examination of all family members as the syndrome usually present with incomplete form. | |||
==Secondary Prevention== | |||
Once a decision to have children is made and the couple conceives, the fetus is monitored during the pregnancy for cardiac evaluation. If a gross cardiac malformation is found, parents receive counseling on continuing with the pregnancy. | |||
==References== | ==References== | ||
Latest revision as of 19:47, 16 September 2013
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mohamed Moubarak, M.D. [2]
Overview
LEOPARD syndrome is a rare autosomal dominant,[1] caused by a mutation in the protein tyrosine phosphatase non-receptor type 11 gene. Many systems can be involved, mostly involving the skin, skeletal and cardiovascular systems, but in other cases they are absent. The word LEOPARD is an acronym for the major features of this disorder, including multiple Lentigines, EKG abnormalities, Ocular hypertelorism, Pulmonic stenosis, Abnormal genitalia, Retardation of growth, and sensorineural Deafness
Historical Perspective
It was first described by Zeisler and Becker with multiple lentigines, hypertelorism, pectus carinatum (protruding breastbone) and prognathism (protrusion of lower jaw) in 1936.[2] In 1962, cardiac abnormalities and short stature were first associated with the condition.[2]
Pathophysiology
LEOPARD syndrome is most commonly caused by missense mutations in the PTPN11 gene. It has also been associated with other gene mutations such as RAF1 and BRAF.
Epidemiology and Demographics
Leopaed syndrome is a rare condition, but the exact birth prevalence is unknown. Approximately 200 patients have been reported.[3] However, LEOPARD syndrome is likely underdiagnosed or misdiagnosed as many of its features are mild and the correct diagnosis might be missed in the absence of lentiginosis.
Natural History, Complications and Prognosis
In general, males are more affected than females. LEOPARD syndrome is not a life threatening diagnosis, cardiomyopathy and other pathologic findings involving the cardiovascular system may be a cause of death in those whose cardiac deformities are profound.
History and Symptoms
LEOPARD syndrome affects many areas in the body. The characteristic feature associated with the condition is brown skin spots called lentigines. Patients are showing a wide spectrum of features include multiple lentigines, facial dysmorphisms, cardiac anomalies, electrocardiographic (EKG) conduction abnormalities, retardation of growth, abnormal genitalia and sensorineural deafness.[4]
Laboratory Findings
Hormonal abnormalities may be revealed in some patients with endocrine system involvement. laboratory studies should include molecular analysis of the PTPN11 and RAF1 genes.[5]
Imaging Studies
Different imaging studies like X-rays, CT scanning, and Echocardiography have been used to detect abnormalities of LEOPARD syndrome.
Medical Therapy
Medical management depend on the symptoms present. Drug therapy for cardiac abnormalities,endocrine, and dermatological issues is recommended.
Surgical Therapy
Different procedures may be necessary in cases with severe outflow tract obstruction[6], patients with cryptorchidism, genitourinary, or severe skeletal deformity.
Primary Prevention
Genetic counseling should be offered before deciding to have children, careful examination of all family members as the syndrome usually present with incomplete form.
Secondary Prevention
Once a decision to have children is made and the couple conceives, the fetus is monitored during the pregnancy for cardiac evaluation. If a gross cardiac malformation is found, parents receive counseling on continuing with the pregnancy.
References
- ↑ Coppin BD, Temple IK (1997). "Multiple lentigines syndrome (LEOPARD syndrome or progressive cardiomyopathic lentiginosis)". J. Med. Genet. 34 (7): 582–6. PMID 9222968.
- ↑ 2.0 2.1 Zeisler, Erwin P. (1936). "GENERALIZED LENTIGO<subtitle>ITS RELATION TO SYSTEMIC NONELEVATED NEVI</subtitle>". Archives of Dermatology. 33 (1): 109. doi:10.1001/archderm.1936.01470070112010. ISSN 0003-987X.
- ↑ Voron DA, Hatfield HH, Kalkhoff RK (1976). "Multiple lentigines syndrome. Case report and review of the literature". Am J Med. 60 (3): 447–56. PMID 1258892.
- ↑ Gorlin RJ, Anderson RC, Blaw M (1969). "Multiple lentigenes syndrome". Am J Dis Child. 117 (6): 652–62. PMID 5771505.
- ↑ Digilio MC, Sarkozy A, de Zorzi A; et al. (2006). "LEOPARD syndrome: clinical diagnosis in the first year of life". Am. J. Med. Genet. A. 140 (7): 740–6. doi:10.1002/ajmg.a.31156. PMID 16523510.
- ↑ Limongelli G, Pacileo G, Marino B, Digilio MC, Sarkozy A, Elliott P; et al. (2007). "Prevalence and clinical significance of cardiovascular abnormalities in patients with the LEOPARD syndrome". Am J Cardiol. 100 (4): 736–41. doi:10.1016/j.amjcard.2007.03.093. PMID 17697839.