Dermatological manifestations in cardiofaciocutaneous syndrome: a prospective multicentric study of 45 mutation-positive patients.

BACKGROUND: Data on dermatological manifestations of cardiofaciocutaneous syndrome (CFCS) remain heterogeneous and almost without expert dermatological classification. OBJECTIVES: To describe the dermatological manifestations of CFCS; to compare them with the literature findings; to assess those discriminating CFCS from other RASopathies, including Noonan syndrome (NS) and Costello syndrome (CS); and to test for dermatological phenotype-genotype correlations. METHODS: We performed a 4-year, large, prospective, multicentric, collaborative dermatological and genetic study. RESULTS: Forty-five patients were enrolled. Hair abnormalities were ubiquitous, including scarcity or absence of eyebrows and wavy or curly hair in 73% and 69% of patients, respectively. Keratosis pilaris (KP), ulerythema ophryogenes (UO), palmoplantar hyperkeratosis (PPHK) and multiple melanocytic naevi (MMN; over 50 naevi) were noted in 82%, 44%, 27% and 29% of patients, respectively. Scarcity or absence of eyebrows, association of UO and PPHK, diffuse KP and MMN best differentiated CFCS from NS and CS. Oral acitretin may be highly beneficial for therapeutic management of PPHK, whereas treatment of UO by topical sirolimus 1% failed. No significant dermatological phenotype-genotype correlation was determined. CONCLUSIONS: A thorough knowledge of CFCS skin manifestations would help in making a positive diagnosis and differentiating CFCS from CS and NS.

[Use of subcutaneous route for comfort care in neonatal palliative population: Systematic review and survey of practices in France]. / Utilisation de la voie sous-cutanée en soins palliatifs néonatals : revue de la littérature et enquête de pratique en France.

INTRODUCTION: Subcutaneous hydration (hypodermoclysis) and drug administration is a widely used method of analgesic therapy in adult palliative care medicine. Very little is known about its use in neonatal medicine. Evidence-based guidelines do not exist due to a lack of data. In this study, the advantages of subcutaneous analgesic therapy in terms of comfort in neonatal palliative care situations were investigated. METHODS: This report details the results of a systematic review associated with a survey in neonatal intensive care units (NICUs) and pediatric palliative care departments (PPCTs) in France. RESULTS: No article was available in the Medline database. In Google®, we found six guidelines that described the use of the subcutaneous route in the pediatric palliative population. The participation rate in the survey was approximately 83 % for French NICUs and 74 % for PPCTs. Eleven percent of NICUs and 27 % of PPCTs had already used subcutaneous drug administration for palliative care, mainly for analgesia and terminal sedation. Limiting factors of its use were mainly alternative options and the lack of data. Nevertheless, 76 % of NICUs and 73 % of PPCTs expressed an interest in the use of the subcutaneous route in NICUs. Ninety-one percent of French NICUs and 80 % of PPCTs were interested in elaborating a protocol using the subcutaneous route for analgesia, anxiolysis, or terminal sedation. CONCLUSION: The subcutaneous route can be advantageous for comfort care in the neonatal palliative population. Studies are needed to define the modalities, pharmacodynamics, and pharmacokinetics of therapeutics in this population.

[Recombinant human erythropoietin in neonates: guidelines for clinical practice from the French Society of Neonatology]. / L'érythropoïétine humaine recombinante chez le nouveau-né : recommandations pour la pratique clinique de la Société française de néonatologie.

OBJECTIVE: 1/To assess the effectiveness and safety of EPO in reducing red blood cell (RBC) transfusions in preterm infants. 2/To provide guidelines for clinical practice in France. METHODS: 1/This systematic evidence review is based on PubMed search, Cochrane library. 2/Using French National Authority for Health methods concerning guidelines for clinical practice. RESULTS: Early EPO reduced the risk of RBC transfusions, donor exposure, and the number of transfusions in very preterm infants (LE2). Late EPO reduced the risk of RBC transfusions and the number of transfusions in very preterm infants (LE2). There is no difference between the effectiveness of early and late EPO (LE2). There is no difference between high-dose and low-dose EPO (LE2). The level of evidence is too low to recommend the intravenous route. EPO has no impact on the rate of bronchopulmonary dysplasia, necrotizing enterocolitis (LE3), and retinopathy of prematurity (LE2). The level of evidence is too low to recommend EPO for neuroprotection in very preterm or term infants. CONCLUSIONS: EPO to reduce RBC transfusion in very preterm infants is recommended (Level A). The optimal time to start therapy is unknown (Level B). The recommended dose is 750IU/kg/week via three subcutaneous injections for 6weeks (Level B).

Expanding the clinical and neuroradiologic phenotype of primary microcephaly due to ASPM mutations.

OBJECTIVE: To determine the spectrum of clinical, neuropsychological, and neuroradiologic features in patients with autosomal recessive primary microcephaly (MCPH) due to ASPM gene mutations. METHODS: ASPM was sequenced in 52 unrelated MCPH probands. In patients with ASPM mutations, we evaluated the clinical phenotype, cognition, behavior, brain MRI, and family. RESULTS: We found homozygous or compound heterozygous ASPM loss-of-function mutations in 11 (22%) probands and 5 siblings. The probands harbored 18 different mutations, of which 16 were new. Microcephaly was severe after 1 year of age in all 16 patients, although in 4 patients the occipital-frontal circumference (OFC) at birth was decreased by only 2 SD. The OFC Z score consistently decreased after birth. Late-onset seizures occurred in 3 patients and significant pyramidal tract involvement in 1 patient. Intellectual quotients ranged from borderline-normal to severe mental retardation. Mild motor delay was noted in 7/16 patients. Language development was delayed in all patients older than 3 years. Brain MRI (n = 12) showed a simplified gyral pattern in 9 patients and several malformations including ventricle enlargement (n = 7), partial corpus callosum agenesis (n = 3), mild cerebellar hypoplasia (n = 1), focal cortical dysplasia (n = 1), and unilateral polymicrogyria (n = 1). Non-neurologic abnormalities consisted of short stature (n = 1), idiopathic premature puberty (n = 1), and renal dysplasia (n = 1). CONCLUSIONS: We provide a detailed description of features associated with ASPM mutations. Borderline microcephaly at birth, borderline-normal intellectual efficiency, and brain malformations can occur in ASPM-related primary hereditary microcephaly.