It Is Not Just the FEV1 That Matters, but the Personal Goals We Reach Along the Way: Qualitative, Multicenter, Prospective, Observational Study.

BACKGROUND: The COVID-19 pandemic has boosted the use of forced expiratory volume in 1 second (FEV1) telemonitoring in pediatric asthma, but a consensus on its most efficient and effective implementation is still lacking. To find answers, it is important to study how such an intervention is perceived, experienced, and used by both patients and health care professionals (HCPs). OBJECTIVE: The aim of this study was to provide perspectives on how FEV1 home monitoring should be used in pediatric asthma. METHODS: This is a qualitative, multicenter, prospective, observational study which included patients with asthma aged 6-16 and HCPs. Primary outcomes were results of 2 surveys that were sent to all participants at study start and after 3-4 months. Secondary outcomes consisted of FEV1 device usage during 4 months after receiving the FEV1 device. RESULTS: A total of 39 participants (26 patients and 13 HCPs) were included in this study. Survey response rates were 97% (38/39) at the start and 87% (34/39) at the end of the study. Both patients and HCPs were receptive toward online FEV1 home monitoring and found it contributive to asthma control, self-management, and disease perception. The main concerns were about reliability of the FEV1 device and validity of home-performed lung function maneuvers. FEV1 devices were used with a median frequency of 7.5 (IQR 3.3-25.5) during the 4-month study period. CONCLUSIONS: Patients and HCPs are receptive toward online FEV1 home monitoring. Frequency of measurements varied largely among individuals, yet perceived benefits remained similar. This emphasizes that online FEV1 home monitoring strategies should be used as a means to reach individual goals, rather than being a goal on their own.

First-year growth in children with Noonan syndrome: Associated with feeding problems?

Children with Noonan syndrome show rapid decline of growth in the first year of life and feeding problems are present in over 50%. The aim of this study was to explore whether growth decelerates because of feeding problems or other Noonan syndrome-related factors. We performed a retrospective, longitudinal cohort study of clinically and genetically diagnosed subjects with Noonan syndrome (n = 143). Questionnaires about the phenotypic-genotypic profile and reported feeding problems were sent to eligible subjects. Data on first-year growth was obtained from growth charts. Ninety-one participants were excluded because of different criteria. A total of 52 subjects with Noonan syndrome were included. The largest decline in weight and length standard deviation score (SDS) occurred in the first 2.5 months after birth (-1.93 and -1.15, respectively), with feeding problems causing a decline of 0.57 SDS in the remaining months. At 1 year, children with feeding problems were on average 290 g lighter and 0.8 cm shorter than children without feeding problems. Weight gain was also negatively influenced by having a PTPN11 mutation (n = 39) and a higher gestational age, whereas children of parents with Noonan syndrome and with a higher birth weight gained more weight. Growth in length was reduced by having cardiac surgery and a higher gestational age, but positively influenced by birth length and maternal height. Growth in children with Noonan syndrome is impaired right after birth and only partially associated with feeding problems. In addition, several specific Noonan syndrome-related factors seem to influence growth in the first year.

Motor performance in children with Noonan syndrome.

Although problems with motor performance in daily life are frequently mentioned in Noonan syndrome, the motor performance profile has never been systematically investigated. The aim of this study was to examine whether a specific profile in motor performance in children with Noonan syndrome was seen using valid norm-referenced tests. The study assessed motor performance in 19 children with Noonan syndrome (12 females, mean age 9 years 4 months, range 6 years 1 month to 11 years and 11 months, SDS 1 year and 11 months). More than 60% of the parents of the children reported pain, decreased muscle strength, reduced endurance, and/or clumsiness in daily functioning. The mean standard scores on the Visual Motor Integration (VMI) test and Movement Assessment Battery for Children 2, Dutch version (MABC-2-NL) items differed significantly from the reference scores. Grip strength, muscle force, and 6 min Walking Test (6 MWT) walking distance were significantly lower, and the presence of generalized hypermobility was significantly higher. All MABC-2-NL scores (except manual dexterity) correlated significantly with almost all muscle strength tests, VMI total score, and VMI visual perception score. The 6 MWT was only significantly correlated to grip strength. This is the first study that confirms that motor performance, strength, and endurance are significantly impaired in children with Noonan syndrome. Decreased functional motor performance seems to be related to decreased visual perception and reduced muscle strength. Research on causal relationships and the effectiveness of interventions is needed. Physical and/or occupational therapy guidance should be considered to enhance participation in daily life.

Perceived motor problems in daily life: Focus group interviews with people with Noonan syndrome and their relatives.

Studies from a patient perspective on motor performance problems in Noonan syndrome in daily life are lacking. The aims of this study were to provide insight into the motor performance problems that people with Noonan syndrome and/or their relatives experienced, the major consequences they suffered, the benefits of interventions they experienced, and the experiences with healthcare professionals they mentioned. We interviewed 10 adults with Noonan syndrome (two were joined by their parent), and 23 mothers (five of whom had Noonan syndrome), nine fathers (one of whom had Noonan syndrome) and one cousin who reported on 28 children with Noonan syndrome. People with Noonan syndrome reported particular problems related to pain, decreased muscle strength, fatigue, and clumsiness, which had an evident impact on functioning in daily life. Most participants believed that problems with motor performance improved with exercise, appropriate physiotherapy guidance, and other supportive interventions. Nevertheless, people with Noonan syndrome and/or their relatives did not feel heard and supported and experienced no understanding of their problems by healthcare professionals. This was the first study from a patient perspective that described the motor performance problems in people with Noonan syndrome, the major consequences in daily life, the positive experiences of interventions and the miscommunication with healthcare professionals. To achieve optimal support, healthcare professionals, as well as people with Noonan syndrome and/or their relatives themselves, should be aware of these frequently presented problems with motor performance. Research on these different aspects is needed to better understand and support people with Noonan syndrome.© 2016 Wiley Periodicals, Inc.

Electrocardiography in Noonan syndrome PTPN11 gene mutation--phenotype characterization.

Noonan syndrome is a developmental disorder with distinctive facial features, short stature and cardiac abnormalities. In this cross-sectional study, we evaluated characteristic electrocardiographic (ECG) findings and cardiac abnormalities in 84 patients with Noonan syndrome, 56 (67%) of who were positive for a PTPN11 mutation. As reported previously, pulmonary stenosis was the most common cardiac abnormality, followed by atrial septal defect and hypertrophic cardiomyopathy. The ECG showed at least one characteristic finding in 50% of cases including left axis deviation in 38 (45%), small R waves in the left precordial leads in 20 (24%) and an abnormal Q wave in 5 (6%) patients with Noonan syndrome. A wide QRS complex was not detected in any of these patients. The characteristic ECG findings of Noonan syndrome patients were not associated with a PTPN11 gene mutation, or with a (specific) cardiac anomaly. We conclude that there are characteristic ECG findings in Noonan syndrome, but the ECG pattern is neither a useful tool for the phenotype characterization of a PTPN11 mutation, nor for the presence or type of cardiac abnormality.

External ear anomalies and hearing impairment in Noonan Syndrome.

OBJECTIVE: This is the first cohort in which hearing impairment and external ear anomalies in Noonan Syndrome are described extensively. METHODS: Retrospective analysis of the otorhinolaryngological and clinical genetic data from 97 Noonan Syndrome (NS) patients. Forty-four NS patients were seen by an otorhinolaryngologist for the analysis of hearing impairment. In our cohort 80 of the 97 patients were genetically tested. In 71 of these mutations were found: in 48 patients a mutation in PTPN11, in 10 patients in SOS1, in 5 patients in SHOC2, in 5 patients in RAF1, in 1 patient in MAP2K2, in 1 patient in KRAS and in 1 patient in A2ML1. RESULTS: External ear anomalies were reported in 75 NS patients (77%). In 69 patients the ears were low-set, 28 patients had posteriorly rotated ears, 14 patients showed protruding ears and 18 had thickened helices. Hearing impairment was detected in 34 NS patients. Nine patients had sensorineural hearing impairment, two a permanent conductive hearing impairment, two other patients had mixed hearing impairment and 20 patients had conductive hearing impairment in the past, caused by otitis media with effusion. Their temporary conductive hearing impairment resolved between the ages of 2 and 18 years. Sensorineural hearing impairment varied between mild high-frequency hearing impairment and profound (uni- and bilateral) hearing impairment and was progressive in three patients. Four NS patients received cochlear implants for their severe sensorineural hearing impairment. The cohort is small for genotype-phenotype correlations, but sensorineural hearing impairment, especially the bilateral severe hearing impairment, was only seen in patients with a PTPN11 mutation. CONCLUSION: NS is characterized by dysmorphic external ear anomalies and both sensorineural and conductive hearing impairment. Audiological examinations are recommended in all patients with Noonan Syndrome.

Prenatal diagnostic testing of the Noonan syndrome genes in fetuses with abnormal ultrasound findings.

In recent studies on prenatal testing for Noonan syndrome (NS) in fetuses with an increased nuchal translucency (NT) and a normal karyotype, mutations have been reported in 9-16% of cases. In this study, DNA of 75 fetuses with a normal karyotype and abnormal ultrasound findings was tested in a diagnostic setting for mutations in (a subset of) the four most commonly mutated NS genes. A de novo mutation in either PTPN11, KRAS or RAF1 was detected in 13 fetuses (17.3%). Ultrasound findings were increased NT, distended jugular lymphatic sacs (JLS), hydrothorax, renal anomalies, polyhydramnios, cystic hygroma, cardiac anomalies, hydrops fetalis and ascites. A second group, consisting of anonymized DNA of 60 other fetuses with sonographic abnormalities, was tested for mutations in 10 NS genes. In this group, five possible pathogenic mutations have been identified (in PTPN11 (n=2), RAF1, BRAF and MAP2K1 (each n=1)). We recommend prenatal testing of PTPN11, KRAS and RAF1 in pregnancies with an increased NT and at least one of the following additional features: polyhydramnios, hydrops fetalis, renal anomalies, distended JLS, hydrothorax, cardiac anomalies, cystic hygroma and ascites. If possible, mutation analysis of BRAF and MAP2K1 should be considered.