Noonan syndrome (NS) is an autosomal dominant multisystem disorder caused by the dysregulation of several genes belonging to the RAS Mitogen Activated Protein Kinase (MAPK) signaling pathway. Incontinentia Pigmenti (IP) is an X-linked, dominantly inherited multisystem disorder.
This study is the first report of the coexistence of Noonan (NS) and Incontinentia Pigmenti (IP) syndromes in the same patient. We report on the clinical phenotype and molecular characterization of this patient. The patient was examined by a pluridisciplinary staff of clinicians and geneticist. The clinical diagnosis of NS and IP was confirmed by molecular investigations. The newborn girl came to our clinics due to flagrant dysmorphia and dermatological manifestations. The clinical observations led to characterize the Incontinentia Pigmenti traits and a suspicion of a Noonan syndrome association. Molecular diagnosis was performed by Haloplex resequencing of 29 genes associated with RASopathies and confirmed the NS diagnosis. The common recurrent intragenic deletion mutation in IKBKG gene causing the IP was detected with an improved PCR protocol.
This is the first report in the literature of comorbidity of NS and IP, two rare multisystem syndromes.
Turner AM. Noonan syndrome. J Paediatr Child Health. 2014;50:E14–E20.
AAL J, Malaquias AC, IJP A, Mendonca BB. Noonan syndrome and related disorders: a review of clinical features and mutations in genes of the RAS/MAPK pathway. Horm Res. 2009;71:185–93.
Nshuti S, Hategekimana C, Uwineza A, Hitayezu J, Mucumbitsi J, Rusingiza EK, et al. Patients with Noonan Syndrome phenotype : spectrum of clinical features and congenital heart defect. Rwanda Medical Journal 2010;68:26–312010;68:26–31.
Rauen KA, Huson SM, Burkitt-Wright E, Evans DG, Farschtschi S, Ferner RE, et al. Recent developments in neurofibromatoses and RASopathies: management, diagnosis and current and future therapeutic avenues. Am J Med Genet Part A. 2015;167:1–10. CrossRef
Guevara BEK, Hsu CK, Liu L, Feast A, Alabado KLP, Lacuesta MPM, et al. Improved molecular diagnosis of the common recurrent intragenic deletion mutation in IKBKG in a Filipino family with incontinentia pigmenti. Aust J Dermatol. 2016;57:150–3. CrossRef
Kuburović V, Vukomanović V, Carcavilla A, Ezquieta-Zubicaray B, Kuburović N. Two cases of LEOPARD syndrome - RAF1 mutations firstly described in children. Turk J Pediatr. 2011;53:687–91. PubMed
Sana ME, Spitaleri A, Spiliotopoulos D, Pezzoli L, Preda L, Musco G, et al. Identification of a novel de novo deletion in RAF1 associated with biventricular hypertrophy in Noonan syndrome. Am J Med Genet Part A. 2014;164:2069–73. CrossRef
Wu X, Simpson J, Hong JH, Kim K, Thavarajah NK, Backx PH, et al. MEK-ERK pathway modulation ameliorates disease phenotypes in a mouse model of Noonan syndrome associated with the Raf1 L613V mutation. Differences. 2011;121:1009–25.
Zarate YA, Lichty AW, Champion KJ, Clarkson LK, Holden KR, Matheus MG. Unique cerebrovascular anomalies in Noonan syndrome with RAF1 mutation. J Child Neurol. 2013;29:1–6.
- Clinical profile of comorbidity of rare diseases in a Tunisian patient: a case report associating incontinentia pigmenti and Noonan syndrome
Karim Ben Ameur
Annachiara De Sandre-Giovannoli
- BioMed Central
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