Craniofacial and cutaneous findings in Noonan, Costello and LEOPARD syndromes

Abstract

Noonan, Costello and LEOPARD syndromes belong to a family of cardiofaciocutaneous disorders and share common genetic traits. As they are associated with a germline mutation in genes encoding proteins involved in RAS/MAPK, patients suffering from these syndromes are at a greater risk of cancer and abnormal myelopoiesis in infancy. Patients with cardio faciocutaneous syndromes share some clinically overlapping syndromes, therefore differential diagnosis can be problematic. In this paper we aim at demonstrating distinctive craniofacial and cutaneous manifestations of Noonan, Costello and LEOPARD syndromes which can be useful for clinicians who aim at treatment of children with rare diseases.

RASopathies: Dermatologists’ viewpoints

“…The earlier nomenclature of Noonan syndrome with multiple lentigines was LEOPARD syndrome, (Lentigines, Electrocardiographic abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormal genitalia, Retarded growth and following Deafness) syndrome. 46,47 Specific missense mutation of PTPN11 or RAF1 constitutes an allelic disorder, 23 the second frequent following Noonan syndrome. 47 Facial and other structural anomalies are grossly similar to Noonan syndrome.…”

“…46,47 Specific missense mutation of PTPN11 or RAF1 constitutes an allelic disorder, 23 the second frequent following Noonan syndrome. 47 Facial and other structural anomalies are grossly similar to Noonan syndrome. 23 Hypertelorism is a consistent feature (100%) [Figure 5].…”

“…23 Hypertelorism is a consistent feature (100%) [Figure 5]. 47 Cutaneous features include multiple café au lait macules (>3 in 80% cases) and lentigines. café au lait macules are present since early infancy, typically darker, linear or rhomboid in shape with irregular, ragged borders [Figure 6a] in contrast to the light brown, round or oval café au lait macules of Neurofibromatosis type 1.…”

“…23 Left ventricular hypertrophic cardiomyopathy is more commoner (80% of the cardiac anomalies) than pulmonary stenosis in Noonan syndrome with multiple lentigines. 17,23,47 Hypertrophic cardiomyopathy may be present at birth well before the appearance of skin lesions, symptoms arise over the years and may lead to life-threatening sequelae. 47 Conduction abnormalities may be present in 75% cases detectable by electrocardiography.…”

“…17,23,47 Hypertrophic cardiomyopathy may be present at birth well before the appearance of skin lesions, symptoms arise over the years and may lead to life-threatening sequelae. 47 Conduction abnormalities may be present in 75% cases detectable by electrocardiography. 47 Sensorineural deafness may be a feature in 15-25% affected children warranting specialised care and annual evaluation.…”