ABSTRACT
Noonan syndrome is a genetically heterogeneous disorder caused by mutations in PTPN11, SOS1, RAF1 and less frequently in KRAS, NRAS or SHOC2. Here, we performed mutation analysis of NRAS and SHOC2 in 115 PTPN11, SOS1, RAF1, and KRAS mutation-negative individuals. No SHOC2 mutations were found, but we identified 3 NRAS mutations in 3 probands. One NRAS mutation was novel. The phenotype associated with germline NRAS mutations is variable. Our results confirm that a small proportion of Noonan syndrome patients carry germline NRAS mutations.
ABSTRACT
Noonan syndrome is characterised by distinct facial stigmata, short stature and congenital cardiopathy. It has a high genetic heterogeneity and mutations in six different genes can be involved. We report a patient with Noonan syndrome and a novel KRAS mutation who presents systemic lupus erythematosus.
Subject(s)
Lupus Erythematosus, Systemic/epidemiology , Lupus Erythematosus, Systemic/genetics , Mutation/genetics , Noonan Syndrome/epidemiology , Noonan Syndrome/genetics , Proto-Oncogene Proteins/genetics , ras Proteins/genetics , Adolescent , Comorbidity , Female , Genetic Predisposition to Disease/genetics , Humans , Lupus Erythematosus, Systemic/diagnosis , Noonan Syndrome/diagnosis , Proto-Oncogene Proteins p21(ras)ABSTRACT
OBJECTIVES: The aim of this preliminary study was to evaluate the efficacy of a 40 degrees supine body position on infant regurgitation, reflux-associated symptoms and acid reflux. INTERVENTION: Thirty of 52 consecutive infants presenting with frequent regurgitation and reflux-associated symptoms occurring mainly during feeding were evaluated in the Multicare AR-Bed (Peos, Ninove, Belgium). The Infant-Gastroesophageal Reflux Questionnaire-Revised (I-GERQ-R) and an oesophageal pH monitoring were performed at inclusion and after 1 week. RESULTS: Eight out of 30 (27%) infants did not tolerate the 40 degrees positioning, and had to be taken out of the study within the first 2 days. However, in 22/30 (73%) infants the I-GERQ-R and acid reflux decreased significantly with the Multicare AR-Bed. The mean duration of use of the Multicare AR-Bed was 3.2 months. CONCLUSION: The results of this pilot study suggest that a specially made bed that nurses the infant at 40 degrees supine body position reduces regurgitation, acid reflux and reflux-associated symptoms. However, the intervention was open, the sample size small and the withdrawal rate was substantial. Larger trials are needed.
Subject(s)
Beds , Gastroesophageal Reflux/prevention & control , Infant Care/methods , Breast Feeding , Equipment Design , Esophageal pH Monitoring , Female , Gastroesophageal Reflux/diagnosis , Humans , Infant , Infant Care/instrumentation , Infant, Newborn , Male , Pilot Projects , Posture , Treatment OutcomeABSTRACT
RAS proteins play key roles in normal cell growth, malignant transformation and learning and memory. Somatic mutations in RAS genes and several of their upstream and downstream molecules result in different human malignancies. In recent years germline mutations in genes coding for components of the RAS signalling cascade have been recognised in a group of phenotypically overlapping disorders, referred to as the neuro-cardio-facial-cutaneous syndromes. These present with variable degrees of psychomotor delay, cardiac abnormalities, facial dysmorphism, short stature, skin defects and increased cancer risk. These findings point to important roles for this evolutionary conserved pathway not only in oncogenesis, but also in cognition, growth and development. Other constitutional disorders caused by mutated RAS pathway genes point to involvement of the RAS-MAPK pathway in immune modulation and vascular development.
Subject(s)
Genetic Diseases, Inborn/genetics , Genetic Diseases, Inborn/physiopathology , MAP Kinase Signaling System/genetics , ras Proteins/genetics , Craniofacial Abnormalities/genetics , Female , Growth Disorders/genetics , Heart Defects, Congenital/genetics , Humans , Male , Neoplasms/genetics , Nervous System Diseases/genetics , Skin Abnormalities/genetics , Syndrome , ras Proteins/metabolismSubject(s)
Craniofacial Abnormalities/diagnosis , Ectodermal Dysplasia/diagnosis , Heart Defects, Congenital/diagnosis , Prenatal Diagnosis , Craniofacial Abnormalities/complications , Ectodermal Dysplasia/complications , Failure to Thrive/complications , Female , Growth Disorders/complications , Heart Defects, Congenital/complications , Humans , MAP Kinase Kinase 2/genetics , Male , Mutation, Missense , Nuchal Translucency Measurement , Polyhydramnios , Pregnancy , Proto-Oncogene Proteins B-raf/genetics , Syndrome , Ultrasonography, PrenatalABSTRACT
UNLABELLED: Babies born after in vitro fertilisation (IVF) are increasing in number, and, although these babies are considered as very precious, no data are available regarding their risk for sudden infant death or apnoea. To evaluate the respiratory maturity of IVF babies, we evaluated the incidence of apnoea during an 8-h polysomnography in 50 consecutively presented IVF babies and in a group of 50 unselected naturally conceived babies. All infants were in good health and matched for term (born > 38 weeks of gestation), birth weight, sex and age at the time of investigation (6-11 weeks post term, median 8.0). There were 24 twins in the IVF and 6 twins in the control group. The incidence of obstructive and isolated central apnoea was comparable in the IVF and control group. However, IVF babies had significantly more periodic breathing episodes than control babies (median 2.30 (range 0-15.30) in IVF, and 1.02 (range 0-11.2) in control babies; P < 0.01). This difference was not related to the higher number of twins in the IVF group. Single IVF babies had significantly more short central apnoeas (5-10 s) than IVF twins (5-10 s) (mean 38.80 +/- 18.63 and 22.33 +/- 13.35; P < 0.001). This difference between single and twin babies was not found in the control group. CONCLUSION: IVF babies have more periodic breathing episodes indicating an immature respiratory pattern than normally conceived babies.
