The case of 17-year-old male with LEOPARD syndrome

Abstract

a b s t r a c t LEOPARD syndrome is a phenotypic expression of mutations in several genes: PTPN11, RAF1, and BRAF. All these genes are responsible for Ras/MARK signaling pathway, which are important for cell cycle regulation, differentiation, growth, and aging. Mutations result in anomalies of skin, skeletal, and cardiovascular systems. The LEOPARD syndrome means lentigines, electrocardiographic conducting abnormalities, ocular hypertelorism, pulmonary stenosis, abnormal genitalia, retarded growth, and deafness. Mutations affect tyrosine proteases, which are included in the signal pathway between the cell membrane and the nucleus. This rare autosomal dominant disorder is characterized by high variability of clinical manifestations. Usually only lentigines are common. Clinical diagnosis is based on lentigines and 2 other symptoms; in cases without lentigines -3 symptoms and at least one affected first-line relative. Herein, we report the case of 17-year-old male who had idiopathic hypertrophic cardiomyopathy with left ventricular obstruction, and supraventricular and ventricular extasystoles, class IVa, left bundle branch block, as a life-threatening manifestation of LEOPARD syndrome. For the treatment of cardiac manifestations of this syndrome, the patient underwent two interventions: (1) mitral valve replacement by mechanical valve Optiform number 27 with surgical resection of left ventricular outflow tract and subaortic membrane excision; (2) implantable cardioverter-defibrillator therapy. <Learning objective: Explain the abbreviation L.E.O.P.A.R.D. (Lentigines, Electrocardiographic conducting abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormal genitalia, Retarded growth, and Deafness). Suspect the signs of L.E.O.P.A.R.D.-syndrome. Realize the etiology. Evaluate probability of this congenital disease on the ground of the clinical manifestations and laboratory data. Measure the significance for health of changes of organs and systems. Choose the main and dangerous manifestation of L.E.O.P.A.R.D.-syndrome. Select the best way for treatment such patients.>

Biventricular Hypertrophic Cardiomyopathy in a Child with LEOPARD Syndrome: a Case Report

“…4 In 90% of the cases, LS occurs due to a missense type of mutation in PTPN11 gene, other involved genes being RAF1 and BRAF, each implicated in less than 5% of cases. 1 In our case a missense-type mutation in PTPN11 gene was also found.…”

“…LS is a rare "neuro-cardio-facial-cutaneous" genetic syndrome, first described by Zeisler and Becker in 1936, in a woman aged 24 years, who presented generalized lentigines, hypertelorism, pectus carinatus, and prognathism. 1 In 1962, Moynahan described the syndrome in association with cardiac anomalies and short stature. 1 LS is more frequently inherited as an autosomal dominant trait, but sporadic cases are also described.…”

“…1 In 1962, Moynahan described the syndrome in association with cardiac anomalies and short stature. 1 LS is more frequently inherited as an autosomal dominant trait, but sporadic cases are also described. 4 In 90% of the cases, LS occurs due to a missense type of mutation in PTPN11 gene, other involved genes being RAF1 and BRAF, each implicated in less than 5% of cases.…”

“…LEOPARD syndrome (LS) is an uncommon genetic autosomal dominant disease that includes the following entities: Lentigines, Electrocardiographic abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormal genitalia, Retarded growth, and Deafness. 1 Th e prevalence of this rare syndrome is not known precisely, though a minimum of 200 patients have been reported. 2,3 LS is the result of diff erent missense-mutations in one of 3 genes -PTPN11 = 90%, RAF1 <5%, BRAF <5%.…”

“…2,3 LS is the result of diff erent missense-mutations in one of 3 genes -PTPN11 = 90%, RAF1 <5%, BRAF <5%. 1 Cardiac abnormalities found in patients with LS include electrocardiographic abnormalities and anatomical malformations, hypertrophic cardiomyopathy (HCM) being currently described as the most frequent abnormality (in up to 80% of cases). 1…”