Cardiac findings in 31 patients with Noonan's syndrome

Bertola, Débora Romeo; Kim, Chong; Sugayama, Sofia Mizuho Miura; Albano, Lilian Maria José; Wagenführ, Jaqueline; Moysés, Regina Lúcia; Gonzalez, Claudette Hajaj

doi:10.1590/s0066-782x2000001100005

Cited by 31 publications

(36 citation statements)

References 8 publications

(12 reference statements)

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“…The type and severity of the cardiac disease can vary from trivial to life-threatening [Burch et al, 1993;Marino et al, 1999;Bertola et al, 2000]. Pulmonic stenosis and HCM are the most common forms of cardiac disease, but a wide range of other lesions, including atrioventricular septal defects and aortic coarctation, are also observed.…”

Section: Clinical Featuresmentioning

confidence: 99%

Noonan Syndrome: Clinical Aspects and Molecular Pathogenesis

2010

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Noonan syndrome (NS) is a relatively common, clinically variable and genetically heterogeneous developmental disorder characterized by postnatally reduced growth, distinctive facial dysmorphism, cardiac defects and variable cognitive deficits. Other associated features include ectodermal and skeletal defects, cryptorchidism, lymphatic dysplasias, bleeding tendency, and, rarely, predisposition to hematologic malignancies during childhood. NS is caused by mutations in the PTPN11, SOS1, KRAS, RAF1, BRAF and MEK1 (MAP2K1) genes, accounting for approximately 70% of affected individuals. SHP2 (encoded by PTPN11), SOS1, BRAF, RAF1 and MEK1 positively contribute to RAS-MAPK signaling, and possess complex autoinhibitory mechanisms that are impaired by mutations. Similarly, reduced GTPase activity or increased guanine nucleotide release underlie the aberrant signal flow through the MAPK cascade promoted by most KRAS mutations. More recently, a single missense mutation in SHOC2, which encodes a cytoplasmic scaffold positively controlling RAF1 activation, has been discovered to cause a closely related phenotype previously termed Noonan-like syndrome with loose anagen hair. This mutation promotes aberrantly acquired N-myristoylation of the protein, resulting in its constitutive targeting to the plasma membrane and dysregulated function. PTPN11, BRAF and RAF1 mutations also account for approximately 95% of LEOPARD syndrome, a condition which resembles NS phenotypically but is characterized by multiple lentigines dispersed throughout the body, café-au-lait spots, and a higher prevalence of electrocardiographic conduction abnormalities, obstructive cardiomyopathy and sensorineural hearing deficits. These recent discoveries demonstrate that the substantial phenotypic variation characterizing NS and related conditions can be ascribed, in part, to the gene mutated and even the specific molecular lesion involved.

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Section: Clinical Featuresmentioning

confidence: 99%

Noonan Syndrome: Clinical Aspects and Molecular Pathogenesis

2010

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“…As there is some phenotypic overlap between the King and Noonan syndromes, the latter a multiple congenital anomaly syndrome inherited in an autosomal dominant pattern, a genetic reIationship between the two syndromes has been supposed 5 . However, Noonan syndrome, that was already reported in Brazilian children [7][8][9] , is not associated with myopathic changes and presents characteristic heart defect in 65% of the patients. The definition that King and Noonan syndromes may represent allelic autosomal dominant entities or be independent and linked to separate loci, depends on further molecular studies 5 .…”

Section: Discussionmentioning

confidence: 93%

King-Denborough Syndrome: report of two Brazilian cases

Reed

Resende

Ferreira

et al. 2002

Arq. Neuro-Psiquiatr.

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-We report on two boys aged 2 and 6 years-old respectively with dysmorphic face, ptosis, downslanting palpebral fissures, hypertelorism, epicanthic folds, low-set ears, malar hypoplasia, micrognathia, high-arched palate, clinodactyly, palmar simian line, pectus excavatum, winging of the scapulae, lumbar lordosis and mild thoracic scoliosis who present congenital hypotonia, slightly delayed motor development, diffuse joint hyperextensibility and mild proximal weakness. The muscle biopsy revealed minimal but identifiable changes represented by size fiber variability, type I fiber predominance and atrophy, perimysial fibrous infiltration and some disarray of the intermyofibrillary network. These cases correspond to the first Brazilian reports of the King-Denborough syndrome and our objective is increasing the awareness of this disorder as these patients are predisposed to developing malignant hyperthermia.KEY WORDS: King-Denborough syndrome, congenital myopathy, malignant hyperthermia. Síndrome de King-Denborough: relato de dois casosRESUMO -Relatamos dois meninos de 2 e 6 anos de idade que apresentam aspectos dismórficos caracterizados por facies alongada, ptose e fenda palpebral anti-mongólica, hipertelorismo, epicanto bilateral, orelhas de implantação baixa, hipoplasia malar, micrognatia, pálato ogival, clinodactilia, prega palmar única, "pectus excavatum", escápulas aladas, lordose lombar e escoliose torácica. Apresentam hipotonia congênita, hiperextensibilidade articular, fraqueza muscular e retardo do desenvolvimento motor. A biópsia muscular revelou em ambos alterações mínimas: variabilidade do tamanho das fibras, predomínio e atrofia de fibras tipo I, discreta infiltração perimisial e desarranjo intermiofibrilar. Os aspectos dismórficos associados à miopatia congênita configuram a síndrome de King-Denborough, da qual acreditamos serem estes os primeiros casos descritos no Brasil. Como a síndrome se acompanha de alto risco de desenvolver hipertermia maligna na indução anestésica, o objetivo deste relato é chamar a atenção para a necessidade do diagnóstico pré-operatório, a fim de evitar esta gravíssima intercorrência. PALAVRAS-CHAVE: síndrome de King-Denborough, miopatia congênita, hipertermia maligna.

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“…The exact pathophysiology of the left QRS axis is still unknown, but a possible explanation could be a counterclockwise rotation of the heart in combination with a conduction defect abnormality [2,3]. There are very few data about the occurrence of one or more of these typical ECG findings in otherwise healthy children.…”

Section: Discussionmentioning

confidence: 99%