Noonan syndrome.

Jan 2013

Roberts AE, Allanson JE, Tartaglia M, Gelb BD.

Source

Department of Cardiology and Division of Genetics, Children's Hospital Boston, Boston, MA 02115, USA. amy.roberts@cardio.chboston.org

Abstract

Noonan syndrome is a genetic multisystem disorder characterised by distinctive facial features, developmental delay, learning difficulties, short stature, congenital heart disease, renal anomalies, lymphatic malformations, and bleeding difficulties. Mutations that cause Noonan syndrome alter genes encoding proteins with roles in the RAS-MAPK pathway, leading to pathway dysregulation. Management guidelines have been developed. Several clinically relevant genotype-phenotype correlations aid risk assessment and patient management. Increased understanding of the pathophysiology of the disease could help development of pharmacogenetic treatments.

Science Direct

See also:

Noonan's Syndrome

Common acute lymphoblastic leukemia in a girl with genetically confirmed LEOPARD syndrome.

Common acute lymphoblastic leukemia in a girl with genetically confirmed LEOPARD syndrome.
J Pediatr Hematol Oncol. 2008 Aug
Laux D, Kratz C, Sauerbrey A.
Pediatric Hematology and Oncology Unit, Department of Pediatrics, HELIOS Klinikum Erfurt, Erfurt, Germany. danilaux@yahoo.de

Germline mutations in PTPN11 gene cause Noonan syndrome and the clinically similar LEOPARD syndrome (LS). LS is a rare congenital developmental disorder characterized by multiple lentigines, cardiac abnormalities, facial dysmorphism, retardation of growth, and deafness. Mutations in exons 7 and 12 of the PTPN11 gene can be identified in nearly 90% of patients with LS. PTPN11 gene encodes for an ubiquitously expressed protein tyrosine phosphatase SHP-2 involved in a variety of intracellular signaling processes in development and hematopoiesis. Somatic PTPN11 mutations contribute to leukemogenesis in children with hematologic malignancies including juvenile myelomonocytic leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, and myelodysplasia. Two cases of leukemia (acute myeloid leukemia) have been reported in children with LS. The authors describe for the first time a girl with genetically confirmed LEOPARD syndrome presenting with common acute lymphoblastic leukemia.

PMID: 18799937 [PubMed - indexed for MEDLINE]

New Treatment for Noonan Syndrome

FDA OK's DRUG FOR NOONAN SYNDROME

June 1, 2007

WASHINGTON, June 1 (UPI) -- The U.S. Food and Drug Administration Friday approved Copenhagen-based Novo Nordisk's Norditropin for children with Noonan syndrome.

The genetic disorder is characterized by short stature, congenital heart defects and unique facial features, notably widely set eyes.

The use of Norditropin -- somatropin injection -- is aimed at treatment of short stature in these individuals.

Fewer than 200,000 people have the condition, prompting the FDA to give Norditropin an orphan drug designation. No other treatment for short stature in these patients is available.

The prevalence of Noonan syndrome has not been determined accurately to date, but most authors report 1 in 1,000 to 1 in 2,500 live births, affecting males and females equally. In addition to heart abnormalities and short stature -- affecting 80 percent of people with Noonan syndrome -- patients may also have visual and hearing deficits, bleeding abnormalities and lack muscle tone.

"Noonan syndrome is a heterogeneous genetic condition in which the clinical features are quite variable," said Alicia Romano, a pediatric endocrinologist at the New York Medical College, in a statement issued by Novo Nordisk.

"Short stature, which can be severe, is one of the most common characteristics. Treatment with Norditropin may help children with Noonan syndrome improve one of the most concerning physical features of the condition."

Norditropin is also approved for treatment of children with growth failure due to inadequate secretion of endogenous growth hormone and for replacement of endogenous growth hormone in adults with growth hormone deficiency.

United Press International

Lymphstasis in a boy with Noonan syndrome: implication for the development of skeletal features.

Lymphstasis in a boy with Noonan syndrome: implication for the development of skeletal features.

Endocr J. 2003 Jun

Ogata T,
Sato S,
Hasegawa Y,
Kosaki K.
Department of Endocrinology and Metabolism, National Research Institute for Child Health and Development, Setagaya, Tokyo 154-8567, Japan.

We report on a Japanese boy with Noonan syndrome who had short stature, bilateral cryptorchidism, poor pubertal development, mild mental retardation, complex cardiac lesions consisting of hypertrophic cardiomyopathy, mitral valve stenosis and insufficiency, subvalvular aortic stenosis, and single coronary artery, and various dysmorphic features including hypertelorism, epicanthic folds, low set malrotated ears, high arched palate, micrognathia, webbed neck, low posterior hairline, shield chest, pectus excavatum, cubitus valgus, borderline short metatarsals, lymphedema, redundant skin, and nail dysplasia.

Because of marked lymphedema in the bilateral lower legs, lymphatic scintigraphy was carried out at 13.3 years of age, indicating extreme lymphstasis in the lower extremities, severe lymphstasis in the forearm, the elbow, and the axillary regions, moderate lymphstasis around the ascending aorta, and mild lymphstasis in the bilateral lungs.

The results, in conjunction with those suggested in Turner syndrome, imply that lymphatic hypoplasia/dysplasia and resultant distended lymphatics and lymphedema are relevant to the development of not only soft tissue and visceral anomalies but also skeletal anomalies in Noonan syndrome.

Endocrine Journal

Mutational Analysis of PTPN11 Gene in Taiwanese Children with Noonan Syndrome

Mutational Analysis of PTPN11 Gene in Taiwanese Children with Noonan Syndrome

Key Words: mutation analysis, Noonan syndrome, PTPN11, SHP-2

Noonan syndrome (NS) is an autosomal dominant disorder presenting with characteristic facies, short stature, skeletal anomalies, and congenital heart defects. Mutations in protein-tyrosine phosphatase, nonreceptor-type 11 (PTPN11), encoding SHP-2, account for 33–50% of NS. This study screened for mutations in the PTPN11 gene in 34 Taiwanese patients with NS. Mutation analysis of the 15 coding exons and exon/intron boundaries was performed by polymerase chain reaction and direct sequencing of the PTPN11 gene.

We identified 10 different missense mutations in 13 (38%) patients, including a novel missense mutation (855T>G, F285L). These mutations were clustered in exon 3 (n = 6) encoding the N-SH2 domain, exon 4 (n = 2) encoding the C-SH2 domain, and in exons 8 (n = 2) and 13 (n = 3) encoding the PTP domain. In conclusion, this study provides further support that PTPN11 mutations are responsible for Noonan syndrome in Taiwanese patients.

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