Leopard sickness: LEOPARD syndrome Information | Mount Sinai

16.05.202128.07.2023 by alexxlab

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LEOPARD syndrome Information | Mount Sinai

Multiple lentigines syndrome; LEOPARD syndrome; NSML

Noonan syndrome with multiple lentigines (NSML) is a very rare inherited disorder. People with this condition have problems with the skin, head and face, inner ear, and heart. The genitals may also be affected.

Noonan syndrome with multiple lentigines was formerly known as LEOPARD syndrome.

Causes

NSML is inherited as an autosomal dominant trait. This means the person only needs the abnormal gene from one parent in order to inherit the disease.

Symptoms

The former name of NSML of LEOPARD stands for the different problems (signs and symptoms) of this disorder:

Lentigines — large number of brown or black freckle-like skin markings that mainly affect the neck and upper chest but can appear all over the body
Electrocardiograph conduction abnormalities — problems with the electrical and pumping functions of the heart
Ocular hypertelorism — eyes that are spaced wide apart
Pulmonary valve stenosis — narrowing of the pulmonary heart valve, resulting in less blood flow to the lungs and causing shortness of breath
Abnormalities of the genitals — such as undescended testicles
Retardation of growth (delayed growth) — including bone growth problems of the chest and spine
Deafness — hearing loss may vary between mild and severe

NSML is similar to Noonan syndrome. However, the main symptom that tells apart the two conditions is that people with NSML have lentigines.

Exams and Tests

The health care provider will perform a physical exam and listen to the heart with a stethoscope.

Tests that may be done include:

ECG and echocardiogram to check the heart
Hearing test
CT scan of the brain
Skull x-ray
EEG to check the brain’s function
Blood tests to check certain hormone levels
Removing a small amount of skin for examination (skin biopsy)

Treatment

Symptoms are treated as appropriate. A hearing aid may be needed. Hormone treatment may be necessary at the expected time of puberty to cause the normal changes to occur.

Laser, cryosurgery (freezing), or bleaching creams may help lighten some of the brown spots on the skin.

Support Groups

More information and support for people with LEOPARD syndrome and their families can be found at:

National Organization for Rare Disorders – rarediseases.org/rare-diseases/leopard-syndrome
Noonan Syndrome Foundation – www.teamnoonan.org/information
Rasopathies Network – rasopathiesnet.org/

Possible Complications

Complications vary and include:

Deafness
Delayed puberty
Heart problems
Infertility

When to Contact a Medical Professional

Call your provider if there are symptoms of this disorder.

Call for an appointment with your provider if you have a family history of this disorder and plan to have children.

Prevention

Genetic counseling is recommended for people with a family history of NSLM who want to have children.

James WD, Elston DM, Treat JR, Rosenbach MA, Neuhaus IM. Melanocytic nevi and neoplasms. In: James WD, Elston DM, Treat JR, Rosenbach MA, Neuhaus IM, eds. Andrews’ Diseases of the Skin: Clinical Dermatology. 13th ed. Philadelphia, PA: Elsevier; 2020:chap 30.

Paller AS, Mancini AJ. Disorders of pigmentation. In: Paller AS, Mancini AJ, eds. Paller and Mancini – Hurwitz Clinical Pediatric Dermatology. 6th ed. Philadelphia, PA: Elsevier; 2022:chap 11.

Last reviewed on: 4/14/2021

Reviewed by: Elika Hoss, MD, Senior Associate Consultant, Mayo Clinic, Scottsdale, AZ. Also reviewed by David Zieve, MD, MHA, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.

LEOPARD Syndrome: Background, Pathophysiology, Etiology

Denny JW, Krishna S, Valiallah N, Fogo A, Natkunarajah J. Images of the month 2: A leopard never changes its spots. Clin Med (Lond). 2020 Mar. 20 (2):231-232. [QxMD MEDLINE Link].
Li R, Baskfield A, Lin Y, Beers J, Zou J, Liu C, et al. Generation of an induced pluripotent stem cell line (TRNDi003-A) from a Noonan syndrome with multiple lentigines (NSML) patient carrying a p. Q510P mutation in the PTPN11 gene. Stem Cell Res. 2019 Jan. 34:101374. [QxMD MEDLINE Link].
Alfurayh N, Alsaif F, Alballa N, Zeitouni L, Ramzan K, Imtiaz F, et al. LEOPARD Syndrome with PTPN11 Gene Mutation in Three Family Members Presenting with Different Phenotypes. J Pediatr Genet. 2020 Dec. 9 (4):246-251. [QxMD MEDLINE Link].
Duat-Rodriguez A, Hernandez-Martin A. [Update on the treatment of RASopathies]. Rev Neurol. 2017 May 17. 64 (s03):S13-S17. [QxMD MEDLINE Link].
Kim J, Kim MR, Kim HJ, Lee KA, Lee MG. LEOPARD Syndrome with PTPN11 Gene Mutation Showing Six Cardinal Symptoms of LEOPARD. Ann Dermatol. 2011 May. 23(2):232-5. [QxMD MEDLINE Link]. [Full Text].
Motegi SI, Yokoyama Y, Ogino S, Yamada K, Uchiyama A, Takeuchi Y, et al. Pathogenesis of Multiple Lentigines in LEOPARD Syndrome with PTPN11 Gene Mutation. Acta Derm Venereol. 2015 Apr 28. [QxMD MEDLINE Link].
Wu J, Zhang H, Zhao G, Wang R. Allosteric inhibitors of SHP2: an updated patent review (2015-2020). Curr Med Chem. 2020 Sep 28. [QxMD MEDLINE Link].
Noda S, Takahashi A, Hayashi T, Tanuma S, Hatakeyama M. Determination of the catalytic activity of LEOPARD syndrome-associated SHP2 mutants toward parafibromin, a bona fide SHP2 substrate involved in Wnt signaling. Biochem Biophys Res Commun. 2016 Jan 22. 469 (4):1133-9. [QxMD MEDLINE Link].
Ogata T, Yoshida R. PTPN11 mutations and genotype-phenotype correlations in Noonan and LEOPARD syndromes. Pediatr Endocrinol Rev. 2005 Jun. 2(4):669-74. [QxMD MEDLINE Link].
webmd.com”>Hanna N, Montagner A, Lee WH, Miteva M, Vidal M, Vidaud M, et al. Reduced phosphatase activity of SHP-2 in LEOPARD syndrome: consequences for PI3K binding on Gab1. FEBS Lett. 2006 May 1. 580(10):2477-82. [QxMD MEDLINE Link].
Kontaridis MI, Swanson KD, David FS, Barford D, Neel BG. PTPN11 (Shp2) mutations in LEOPARD syndrome have dominant negative, not activating, effects. J Biol Chem. 2006 Mar 10. 281(10):6785-92. [QxMD MEDLINE Link].
Wang Y, Chen C, Wang DW. Leopard syndrome caused by heterozygous missense mutation of Tyr 279 Cys in the PTPN11 gene in a sporadic case of Chinese Han. Int J Cardiol. 2014 Jul 1. 174(3):e101-4. [QxMD MEDLINE Link].
Begic F, Tahirovic H, Kardaševic M, Kalev I, Muru K. Leopard syndrome: a report of five cases from one family in two generations. Eur J Pediatr. 2014 Jun. 173(6):819-22. [QxMD MEDLINE Link].
Tartaglia M, Martinelli S, Stella L, Bocchinfuso G, Flex E, Cordeddu V, et al. Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease. Am J Hum Genet. 2006 Feb. 78(2):279-90. [QxMD MEDLINE Link].
Ucar C, Calyskan U, Martini S, Heinritz W. Acute myelomonocytic leukemia in a boy with LEOPARD syndrome (PTPN11 gene mutation positive). J Pediatr Hematol Oncol. 2006 Mar. 28(3):123-5. [QxMD MEDLINE Link].
Laux D, Kratz C, Sauerbrey A. Common acute lymphoblastic leukemia in a girl with genetically confirmed LEOPARD syndrome. J Pediatr Hematol Oncol. 2008 Aug. 30(8):602-4. [QxMD MEDLINE Link].
Kalidas K, Shaw AC, Crosby AH, Newbury-Ecob R, Greenhalgh L, Temple IK, et al. Genetic heterogeneity in LEOPARD syndrome: two families with no mutations in PTPN11. J Hum Genet. 2005. 50(1):21-5. [QxMD MEDLINE Link].
Writzl K, Hoovers J, Sistermans EA, Hennekam RC. LEOPARD syndrome with partly normal skin and sex chromosome mosaicism. Am J Med Genet A. 2007 Nov 1. 143A(21):2612-5. [QxMD MEDLINE Link].
Lodish MB, Stratakis CA. The differential diagnosis of familial lentiginosis syndromes. Fam Cancer. 2011 Sep. 10(3):481-90. [QxMD MEDLINE Link].
Voron DA, Hatfield HH, Kalkhoff RK. Multiple lentigines syndrome. Case report and review of the literature. Am J Med. 1976 Mar. 60(3):447-56. [QxMD MEDLINE Link].
Lee CL, Tan LTH, Lin HY, Hwu WL, Lee NC, Chien YH, et al. Cardiac manifestations and gene mutations of patients with RASopathies in Taiwan. Am J Med Genet A. 2020 Feb. 182 (2):357-364. [QxMD MEDLINE Link].
Digilio MC, Sarkozy A, de Zorzi A, Pacileo G, Limongelli G, Mingarelli R, et al. LEOPARD syndrome: clinical diagnosis in the first year of life. Am J Med Genet A. 2006 Apr 1. 140(7):740-6. [QxMD MEDLINE Link].
Jurko T, Jurko A Jr, Krsiakova J, Jurko A, Minarik M, Mestanik M. Importance of cardiovascular examination in patients with multiple lentigines: two cases of LEOPARD syndrome with hypertrophic cardiomyopathy. Acta Clin Belg. 2018 May 2. 1-4. [QxMD MEDLINE Link].
Bujaldon AR. LEOPARD syndrome: what are café noir spots?. Pediatr Dermatol. 2008 Jul-Aug. 25(4):444-8. [QxMD MEDLINE Link].
Xing Q, Chen X, Wang M, Bai W, Peng X, Gao R, et al. A locus for familial generalized lentiginosis without systemic involvement maps to chromosome 4q21. 1-q22.3. Hum Genet. 2005 Jul. 117(2-3):154-9. [QxMD MEDLINE Link].
Aragüés IH, Domínguez MC, Blanco VP, Zubicaray BE, Fernández RS. LEOPARD syndrome and multiple granular cell tumors: An underreported association?. Indian J Dermatol Venereol Leprol. 2016 Jan-Feb. 82 (1):77-9. [QxMD MEDLINE Link].
Limongelli G, Sarkozy A, Pacileo G, Calabro P, Digilio MC, Maddaloni V, et al. Genotype-phenotype analysis and natural history of left ventricular hypertrophy in LEOPARD syndrome. Am J Med Genet A. 2008 Mar 1. 146A(5):620-8. [QxMD MEDLINE Link].
Limongelli G, Pacileo G, Marino B, Digilio MC, Sarkozy A, Elliott P, et al. Prevalence and clinical significance of cardiovascular abnormalities in patients with the LEOPARD syndrome. Am J Cardiol. 2007 Aug 15. 100(4):736-41. [QxMD MEDLINE Link].
Nakagama Y, Inuzuka R, Ichimura K, Hinata M, Takehara H, Takeda N, et al. Accelerated Cardiomyocyte Proliferation in the Heart of a Neonate With LEOPARD Syndrome-Associated Fatal Cardiomyopathy. Circ Heart Fail. 2018 Apr. 11 (4):e004660. [QxMD MEDLINE Link].
Yagubyan M, Panneton JM, Lindor NM, Conti E, Sarkozy A, Pizzuti A. LEOPARD syndrome: a new polyaneurysm association and an update on the molecular genetics of the disease. J Vasc Surg. 2004 Apr. 39(4):897-900. [QxMD MEDLINE Link].
Porciello R, Divona L, Strano S, Carbone A, Calvieri C, Giustini S. Leopard syndrome. Dermatol Online J. 2008 Mar 15. 14(3):7. [QxMD MEDLINE Link].
Rudolph G, Haritoglou C, Kalpadakis P, Boergen KP, Meitinger T. [LEOPARD syndrome with iris-retina-choroid coloboma. Discordant findings in monozygotic twins (MIM # 151 100)]. Ophthalmologe. 2001 Nov. 98(11):1101-3. [QxMD MEDLINE Link].
Spatola M, Wider C, Kuntzer T, Croquelois A. PTPN11 mutation manifesting as LEOPARD syndrome associated with hypertrophic plexi and neuropathic pain. BMC Neurol. 2015 Apr 16. 15:55. [QxMD MEDLINE Link]. [Full Text].
García-Gil MF, Álvarez-Salafranca M, Valero-Torres A, Ara-Martín M. Melanoma in Noonan Syndrome With Multiple Lentigines (Leopard Syndrome): A New Case. Actas Dermosifiliogr. 2020 Sep. 111 (7):619-621. [QxMD MEDLINE Link].
Cheng YP, Chiu HY, Hsiao TL, Hsiao CH, Lin CC, Liao YH. Scalp melanoma in a woman with LEOPARD syndrome: possible implication of PTPN11 signaling in melanoma pathogenesis. J Am Acad Dermatol. 2013 Oct. 69(4):e186-7. [QxMD MEDLINE Link].
Jozwiak S, Schwartz RA, Janniger CK. LEOPARD syndrome (cardiocutaneous lentiginosis syndrome). Cutis. 1996 Apr. 57(4):208-14. [QxMD MEDLINE Link].
Jozwiak S, Schwartz RA, Janniger CK, Zaremba J. Familial occurrence of the LEOPARD syndrome. Int J Dermatol. 1998 Jan. 37(1):48-51. [QxMD MEDLINE Link].

Thrombosis, hangover and 5 more reasons why a marble pattern appears on the skin

Health

The skin can become marble on the arms, legs, stomach. Livedo, angiitis or, more simply, marbling of the skin is familiar to many, for example, occurs in children when freezing. We understand when this condition is dangerous.

June 11, 2022

Source:: iStockphoto

Irregular coloration of the skin, resembling a pattern on marble, is called in medicine a fancy term – “livedo”. These are the features of the response of blood vessels in the area of the skin and subcutaneous tissue, arising from disruptions in the functioning of the autonomic nervous system. As a result, some of the vessels are too dilated, there is too much blood inside them, while the neighboring ones are in spasm and are not filled with blood at all.

Outwardly, it looks like patches of pale and red color, cyanotic, purple, reddish-blue, intricately combined with each other. They can be subtle or very pronounced, appear only occasionally or are quite persistent. “Doctor Peter” talked about the reasons for this condition with Nikolai Zherdev, a cardiovascular surgeon at the ABIA clinic.

Not always vasospasm

Skin marbling, also known as livedo reticularis, is commonly thought to be caused by spasm of blood vessels close to the surface of the skin.

But to be more precise, such skin coloration occurs due to impaired blood flow in small and medium-sized vessels – capillaries, arterioles. Changes in skin coloration are formed in conditions of vasculopathy (vascular pathologies) due to:

vasospasm,
hypercoagulable conditions, thrombosis,
increased blood viscosity
or vascular embolism,
and also in combination with existing vasculitis (inflammation of the vascular walls).

Due to disturbances in the normal blood flow within the vessels, the skin, usually on the legs, looks mottled with a purple tint, as if covered with a mesh pattern with clear boundaries.

If it’s cold, spots appear

Often, marbling of the skin appears as a result of simple hypothermia, or vice versa, severe overheating. Surely, many of you have observed marbling of the skin after going to the bath or sauna, and also noticed how the color of the hands changes after a long stay in the cold without gloves or mittens.

In this case, the body reacts in this way to a sharp change in ambient temperature. No action is needed in this case, the marbling resolves spontaneously without any treatment.

Circulatory problems and marbling

Since these are circulatory disorders, one of the leading causes of such a spotted pattern is existing diseases, pathologies and conditions in which blood flow in the veins or arteries is disturbed . In the development of livedo, a decrease in the tone of the veins and stagnation of a small volume of blood in them plays a certain role. Especially often the blood stagnates in the legs and in the area of the saphenous veins. Against the background of low ambient temperatures, an increasingly bright pattern appears on the skin.

More often complaints of spotting or marbling occur in people who suffer from heart failure, have episodes of increased pressure. Local changes in skin color are possible with prolonged standing on your feet, with sedentary work. A sharp change in the color of the limb with the appearance of marbling can give fat or air embolism, thrombosis.

Drank, smoked – turned pale

Against the background of smoking, marbling of the skin on the arms or legs often occurs as a result of the reaction of blood vessels to the effects of toxins – nicotine and combustion products, including carbon monoxide. Therefore, longtime smokers often have pale, marbled skin due to vascular problems.

The intake of alcohol, followed by the formation of its decomposition products, also has a negative effect on blood vessels. Against the background of taking strong drinks, the vessels first expand, but then they can sharply narrow. This gives the effect of marbling. Especially it can be expressed in the morning, against the background of a hangover syndrome.

When should you see a doctor?

There are a number of situations in which you should not delay a visit to the doctor. These are:

Marbling does not disappear after warming or normalizing the temperature around.
Painful lumps and nodules are felt in the skin.
Ulcers began to appear on the skin.
In addition to the marbling of the skin, you have other complaints and symptoms.
You already know that there are some problems with the vessels of the extremities.
You are already seeing a rheumatologist for systemic lupus erythematosus or another systemic disease.

Text author: Alena Paretskaya

Leopard skin | WEBSITE OF THE HERBALIST EFREMOV A.P.

A.P. Efremov

Leopards, like many other cats with spotted coloration, look very impressive and attractive. In addition, the spotted coloration helps them to camouflage themselves well in the environment while hunting. But what is good for leopards is not always good for humans. So the spotty coloration of the skin not only does not decorate a person, but, on the contrary, causes a hostile feeling in many. The culprit of the “leopard skin” in humans is a microscopic yeast fungus Malassezia furfur (aka Pityrosporum orbiculare) , and the disease it provokes is called pityriasis versicolor or sun lichen.

This disease is ubiquitous, but more common in countries with hot and humid climates. They usually get sick at a young age. This fungus lives on the skin of almost all people, but only causes disease in some.

The risk of developing pityriasis versicolor increases in people suffering from excessive sweating, a certain chemical composition of sweat that is favorable for the causative agent pH of the skin, with concomitant diseases: endocrine disorders (diabetes mellitus), chronic diseases of the gastrointestinal tract, and immunodeficiency. In recent years, information has emerged about the genetic predisposition of some people to develop pityriasis versicolor. Often this disease develops against the background of pulmonary tuberculosis, lymphogranulomatosis, since these diseases are often accompanied by excessive sweating.

This disease is not contagious and does not cause any discomfort, except for moral discomfort. However, it can form an inferiority complex in young people, especially girls, and generally affect their behavior and even fate. As a rule, people with such a skin defect are embarrassed to expose their body on the beach, which makes their vacation at sea inferior and does not bring pleasure. And where, if not on the beach, you can still demonstrate your young beautiful body.

One of the common causes of this disease in perfectly healthy people is sunburn of the skin, which leads to a sharp drop in its protective properties. “Lucky” and I was ill with this disease in my younger years. Before the end of military service in Georgia, I decided to get a demobilization tan and lay under the scorching southern sun for almost a whole day. The result was a severe skin burn, after which I turned into a young leopard.

Pityriasis versicolor begins, as a rule, with the appearance of a small, not very inflamed and pink spot that does not rise above the surface of the skin. Sometimes the color may be yellowish or coffee-colored. Gradually, the spot is overgrown with “brothers”, they merge into bizarre outlines, forming “geographical” patterns. Elements of pityriasis versicolor are located on the skin of the chest, upper back, neck, shoulders.

Spots look lighter against the background of tanned skin. Spots tend to merge to form large foci, but can exist in isolation. Inflammatory phenomena are absent, there is a slight pityriasis peeling.

Upon returning home, I had to go to a dermatovenerological dispensary, where I was prescribed an alcohol solution of salicylic acid with resorcinol. A long-term and unsuccessful struggle with lichen began. For a while, there was an improvement, and then the skin was again colored with leopard spots. Years later, when I already became well versed in medicinal plants, I finally found a radical and affordable remedy for pityriasis versicolor, thanks to which I quickly got rid of this disease. It turned out to be hellebore water, which is sold in any pharmacy. Hellebore water is a tincture of hellebore roots Lobel (Veratrum lobelianum).

The treatment is very simple: it is necessary for 10-15 days (3-5 procedures are enough) in the evening with a cotton swab moistened with hellebore water to lubricate the areas of skin affected by lichen.