This association is a non-profitable organization of social utility, addressed to patients with Noonan Syndrome as well as with all related Syndromes (LEOPARD, CFC, Costello), to their families, to the scientific world and to the whole social community to spread available information on these genetic diseases, to foster and support scientific research, to provide support and psychological and social assistance, and to protect and safeguard the rights of affected people.
Noonan Syndrome is a genetic disease, which occurs in approximately 1 in 1,000 to 2,500 people. Mutations in the genes causing Noonan syndrome may happen casually, at the time of conception or they may be inherited from one affected parent.
Diagnosis of Noonan syndrome is made clinically by observation of key features. The main genetic causes of this syndrome have been delineated by progressed research. Approximately 50 percent of individuals with Noonan syndrome have mutations in the PTPN11 gene, which is located in chromosome 12. Mutation affecting the SOS1, RAF1 and KRAS account for approximatly 15%.
This syndrome is inherited in an autosomal dominant pattern, which means that the gene-disease is inherited from one affected parent by half of his/her children, on average, independently from their sex. In more than 50% of the cases, the syndrome results from new mutations in the gamete of a not affected parent.
Clinical Diagnosis of Noonan Syndrome
The main disease characteristics are not always present in all affected persons and they may vary considerably. Noonan syndrome is characterized by congenital heart defect, characteristic facies (hypertelorism, ocular abonormalities such as oblique eyelids rotated downwards and eyelid ptosis, low set and backwards rotated ears with a thick helix), unusual chest shape, broad or webbed neck, kidney malformations, abnormalities in male genitals (undescended testicles or cryptorchidism), short stature, feeding disorders during infancy, bleeding problems for varied coagulation defects, lymphatic dysplasias, developmental delay of variable degree, usually mild. Congenital heart disease occurs in 50% of individuals and the most common heart defects are pulmonary valve stenosis and hypertrophic cardiomyopathy. Additional heart diseases may more rarely be diagnosed.
Clinical Diagnosis of Related Diseases
LEOPARD Syndrome is a multiple lentiginosis disease mostly involving the skin. It is also characterized by congenital heart defect, characteristic facies, short stature, cryptorchidism and sensorineural deafness. Lentiginosis is not usually detected at birth , but may appear progressively at the age of 4-5 years. The most common congenital heart diseases are hypertrophic cardiomyopathy and pulmonary valve stenosis. Also known is the association with heart rhythm defects. LEOPARD syndrome is a genetic disease which is inherited in an autosomal dominant pattern. The disease is mostly caused by mutations in the PTPN11 gene which, however, differ from mutations occurring in Noonan syndrome. A small percentage of cases show mutations in RAF1.
Cardiofaciocutaneous Syndrome (CFC)
The main characteristics of the Cardiofaciocutaneous Syndrome (CFC) are psychomotor and language retardation, feeding disorders in the first years of life, distinctive facial malformations, congenital heart disease and a range of skin abnormalities. A distinctive characteristic is sparse, brittle, curly scalp hair, absent or rare eyebrows and thick, scaly skin, with tendency to eczema and keratosis pilaris. This is an extremely rare disease which is linked to “de novo” mutations in the KRAS, BRAF, MEK1 and MEK2 genes.
This condition is characterized by delayed development and mental retardation, difficulty feeding and slow growth, heart abnormalities like congenital heart disease and very fast heartbeat, distinctive facial features, sparse and thin scalp hair at birth, which becomes frizzy at a later stage, loose folds of extra skin (especially on the hands and feet), and unusually flexible joints, increased risk of developing skin papillomas and cancerous tumors. The most common heart diseases are pulmonary valve stenosis, hypertrophic cardiomyopathy, atrial and ventricular defects often associated with heartbeat disorders like atrial tachycardia. This syndrome is caused by mutations in HRAS.
- dr. Maria Cristina Digilio, Pediatrist Geneticist MD, Bambino Gesú Pediatric Hospital – Rome
- prof. Giovanni Battista Ferrero, Pediatrist, University of Turin
- prof. Bruno Marino, Pediatrist Cardiologist, Policlinico Umberto I – La Sapienza University – Rome
- prof. Laura Mazzanti, Pediatrist Syndromes Expert, Azienda Ospedaliera Universitá S. Orsola – Malpighi – Bologna
- prof. Angelo Selicorni, Pediatrist Geneticist, Fondazione Policlinico – Milan
- prof. Giuseppe Zampino, Pediatrist Geneticist, Università Cattolica del Sacro Cuore – Rome
The ANGELI NOONAN Association is affiliate to:
UNIAMO FIMR, Italian Federation Rare Diseases
EURORDIS, European Federation Rare Diseases