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Frontiers in Pediatrics 2021Cyproheptadine is a first-generation H1-antihistamine drug first that was distributed in the 1960s. While its orexigenic effect was observed early, cyproheptadine is...
Cyproheptadine is a first-generation H1-antihistamine drug first that was distributed in the 1960s. While its orexigenic effect was observed early, cyproheptadine is not yet authorized for this indication in all countries today. There is an increasing medical interest and demand for the orexigenic effect of cyproheptadine, especially in children with poor appetite. As cyproheptadine might be evaluated in future clinical trials, we wanted to assess its safety profile. Using the French national pharmacovigilance database, we retrospectively analyzed all pediatric and adult reports of adverse effects of cyproheptadine recorded since its first distribution in France. Next, we performed a systematic review of the literature of cyproheptadine adverse effects. Since 1985, 93 adverse effects were reported in the French pharmacovigilance database (adults 81.7%, children 18.3%); these were mainly neurological symptoms ( = 38, adults 71%, children 28.9%), and hepatic complications ( = 15, adults 86.7%, children 13.3%). In the literature, the most frequent adverse effect reported was drowsiness in adults or children, and five case reports noted liver complications in adults. We estimated the frequency of hepatic adverse effects at 0.27 to 1.4/1000, regardless of age. Cyproheptadine can be considered a safe drug. Mild neurological effects appear to be frequent, and hepatotoxicity is uncommon to rare. Randomized controlled trials are needed to evaluate the safety and efficacy of cyproheptadine before authorization for appetite stimulation, especially in young children as studies at this age are lacking. Possible hepatic complications should be monitored, as very rare cases of liver failure have been reported.
PubMed: 34676184
DOI: 10.3389/fped.2021.712413 -
Orphanet Journal of Rare Diseases Oct 2021Pierre Robin sequence (PRS) is a heterogeneous condition involving retro(micro)gnathia, glossoptosis and upper airway obstruction, very often with posterior cleft...
BACKGROUND
Pierre Robin sequence (PRS) is a heterogeneous condition involving retro(micro)gnathia, glossoptosis and upper airway obstruction, very often with posterior cleft palate. Patients with PRS, either isolated or associated with Stickler syndrome have good intellectual prognosis. Nevertheless, the quality of life in adolescence and the phonatory and morphological outcomes are rarely analysed. We assessed the phonatory and morphological outcomes of 72 cognitively unimpaired adolescents with PRS, studied their oral (COHIP-SF19), vocal (VHI-9i) and generic quality of life (QoL; KIDSCREEN-52), and searched for determinants of these outcomes.
RESULTS
Two-thirds of our adolescents retained low or moderate phonation difficulties, but risk factors were not identified. For 14%, morphological results were considered disharmonious, with no link to neonatal retrognathia severity. Only one vs two-stage surgery seemed to affect final aesthetic results. The oral QoL of these adolescents was comparable to that of control patients and was significantly better than that of children with other craniofacial malformations (COHIP-SF19 = 17.5, 15.4 and 25.7, respectively). The oral QoL of the adolescents with non-isolated PRS was significantly worse (COHIP-SF19 = 24.2) than that of control patients and close to that of children with other craniofacial malformations. The vocal QoL of the adolescents (mean [SD] VHI-9i = 7.5 [5.4]) was better than that of patients with other voice pathologies and better when phonation was good. The generic QoL of the adolescents was satisfactory but slightly lower than that of controls, especially in dimensions concerning physical well-being, relationships and autonomy. QoL results were lower for adolescents with non-isolated than isolated PRS. Only non-isolated PRS and low oral QoL affected generic QoL.
CONCLUSION
Morphological or phonatory impairments remain non-rare in adolescents with PRS but do not seem to be directly responsible for altered QoL. These adolescents, especially those with non-isolated PRS, show self-confidence and social-relation fragility. We must focus on long-term functional and psychological results for PRS patients and improve therapy protocols and follow-up, notably those affecting the oral aspects of the disease.
Topics: Adolescent; Connective Tissue Diseases; Cross-Sectional Studies; Humans; Phonation; Pierre Robin Syndrome; Quality of Life
PubMed: 34670591
DOI: 10.1186/s13023-021-02072-0 -
Korean Journal of Orthodontics Sep 2021To investigate the phenotypes and predominant skeletodental pattern in pre-adolescent patients with Pierre-Robin sequence (PRS).
OBJECTIVE
To investigate the phenotypes and predominant skeletodental pattern in pre-adolescent patients with Pierre-Robin sequence (PRS).
METHODS
The samples consisted of 26 Korean pre-adolescent PRS patients (11 boys and 15 girls; mean age at the investigation, 9.20 years) treated at the Department of Orthodontics, Seoul National University Dental Hospital between 1998 and 2019. Dental phenotypes, oral manifestation, cephalometric variables, and associated anomalies were investigated and statistically analyzed.
RESULTS
Congenitally missing teeth (CMT) were found in 34.6% of the patients (n = 9/26, 20 teeth, 2.22 teeth per patient) with 55.5% (n = 5/9) exhibiting bilaterally symmetric missing pattern. The mandibular incisors were the most common CMT (n = 11/20). Predominant skeletodental patterns included Class II relationship (57.7%), posteriorly positioned maxilla (76.9%) and mandible (92.3%), hyper-divergent pattern (92.3%), high gonial angle (65.4%), small mandibular body length to anterior cranial base ratio (65.4%), linguoversion of the maxillary incisors (76.9%), and linguoversion of the mandibular incisors (80.8%). Incomplete cleft palate (CP) of hard palate with complete CP of soft palate (61.5%) was the most frequently observed, followed by complete CP of hard and soft palate (19.2%) and CP of soft palate (19.2%) ( < 0.05). However, CP severity did not show a significant correlation with any cephalometric variables except incisor mandibular plane angle ( < 0.05). Five craniofacial and 15 extra-craniofacial anomalies were observed (53.8% patients); this implicated the need of routine screening.
CONCLUSIONS
The results might provide primary data for individualized diagnosis and treatment planning for pre-adolescent PRS patients despite a single institution-based data.
PubMed: 34556588
DOI: 10.4041/kjod.2021.51.5.337 -
Seminars in Fetal & Neonatal Medicine Dec 2021
Review
Topics: Airway Obstruction; Child; Humans; Infant; Pierre Robin Syndrome; Quality of Life; Retrospective Studies; Treatment Outcome
PubMed: 34556442
DOI: 10.1016/j.siny.2021.101287 -
Heliyon Sep 2021This case-control study was conducted to determine the distribution of cleft lip and/or palate, its association with family history, syndromes and serous otitis media...
OBJECTIVE
This case-control study was conducted to determine the distribution of cleft lip and/or palate, its association with family history, syndromes and serous otitis media (SOM), and its relation with several risk factors.
METHODS
The case group comprised of 133 children born with cleft lip and/or palate, and the control was 133 non-cleft children born full-term. Data was collected including age, gender, origin and risk factors for cleft lip and palate from patients' files, interviewing supervising doctors, and the patient. Data was then filled out into Excel and underwent statistical analysis using the Goodness of Fit Test and Chi-Square to determine the significance of the results.
RESULTS
Cleft lip and/or palate (CL/P) was slightly higher among males (51.9%). Combined cleft lip and palate (CLP) was the most common presentation (42.1%). Cleft lips (CL) were mostly complete cleft (51,5%) incomplete cleft comprised (41.1%), In the sample 35.4% of the cases were bilateral, 32.3% were right unilateral, 28.3% were left unilateral and 4% were median cleft. Cleft palate (CP) was mostly complete (46.6%) there were incomplete clefts (40%), and the remainder were submucosal (13.4%). Isolated CL and combined CLP were higher in males (51.6%, 62.5% respectively). Both isolated CP and Tessier anomaly were more common in females (64.7% and 58.3% respectively). consanguineous marriages accounted for 36.1% of cases. 21.8% of the sample had a first-degree relative and 24.8% had a second degree relative born with CL/P. There were only 7 cases (0.05%) of syndromic CL/P: Down's (4), Pierre Robin's (2), and Van der Woude Syndrome (1). A relationship was found between CL/P and the risk factors: taking anticonvulsants (without specifying the drug) (p = 0.025, OR = 10.73 C.I. 95%), taking retinoic acid (p-value = 0.049, OR = 4.75 C.I. 95%), not consuming folic acid (p-value = 0.00, OR = 28.23 C.I. 95%), and smoking cigarettes (p-value = 0.046, OR = 2.00 C.I. 95%). There was no relationship with maternal alcohol consumption or maternal diabetes (p-values = 0.652 and 0.210, respectively). SOM was present in 63.2% of patients with CL/P and were mostly isolated CP.
CONCLUSION
CL/P was only slightly higher among males. The most common condition was CLP. There was higher incidence of CL/P among second-degree relatives than first degree. Down's, Pierre Robin's, and Van der Woude Syndromes may be associated with CL/P. Taking anticonvulsants, taking retinoic acid, not consuming folic acid, and smoking cigarettes all have a role in the incidence of CL/P. More than half of the sample had an associated SOM.
PubMed: 34541358
DOI: 10.1016/j.heliyon.2021.e07957 -
Molecular Cytogenetics Sep 20214q deletion syndrome is a rare chromosomal disorder that mostly arises de novo. The syndrome is characterized by craniofacial dysmorphism, digital abnormalities,...
BACKGROUND
4q deletion syndrome is a rare chromosomal disorder that mostly arises de novo. The syndrome is characterized by craniofacial dysmorphism, digital abnormalities, skeletal alterations, heart malformations, developmental delay, growth retardation, Pierre Robin sequence, autistic spectrum and attention deficit-hyperactivity disorder, although not every patient shows the same features. Array comparative genomic hybridization (aCGH) use improves the detection of tiny chromosomal deletions and allows for a better understanding of genotype-phenotype correlations in affected patients. We report the case of a 6-year-old female patient showing mild dysmorphic features, mild mental disabilities and a coagulation disorder as a consequence of a de novo del(4)(q34.1) characterized by aCGH.
CASE PRESENTATION
A 6-year-old female patient exhibited special craniofacial features, such as backward-rotated ears, upslanted palpebral fissures, broad nasal bridges, anteverted nares, broad nasal alae, smooth philtrums, smooth nasolabial folds, thin lips, horizontal labial commissures, and retrognathia. In the oral cavity, maxillary deformation, a high arched palate, agenesis of both mandibular canines and fusion of two mandibular incisors were observed. She also displayed bilateral implantation of the proximal thumbs, widely spaced nipples, dorsal kyphosis, hyperlordosis, and clitoral hypertrophy. In addition, the patient presented with coagulopathy, psychomotor delay, attention deficit-hyperactivity disorder, and mild mental disability. A chromosomal study showed the karyotype 46,XX,del(4)(q34.1), while an aCGH analysis revealed an 18.9 Mb deletion of a chromosome 4q subtelomeric region spanning 93 known genes.
CONCLUSION
The clinical manifestations of this patient were similar to those reported in other individuals with 4q deletion syndrome. Although most of the patients with a 4q34 terminal deletion share similarities, variations in phenotype are also common. In general, clinical effects of chromosomal deletion syndromes depend on the length of the deleted chromosomal segment and, consequently, on the number of lost genes; however, in all of these syndromes, there is no simple correlation between the phenotype and the chromosomal region involved, particularly in cases of 4q deletion.
PubMed: 34481514
DOI: 10.1186/s13039-021-00564-z -
Indian Journal of Otolaryngology and... Sep 2021Hereditary hearing loss accounts for nearly 60% of deafness in developed countries and about 30% of them are syndromic. Pierre Robin Syndrome is one such condition. The...
Hereditary hearing loss accounts for nearly 60% of deafness in developed countries and about 30% of them are syndromic. Pierre Robin Syndrome is one such condition. The patient with this syndrome usually presnts with triad of micrognathia, glossoptosis and cleft palate. Hearing loss is mostly conductive but there can be sensorineural hearing loss also. Here we present a case of Pierre Robin Syndrome who presented with congenital hearing loss. He also had bilateral serous otitis media. He underwent cochlear implant surgery and was prescribed antihistaminics and steroid spray for middle ear effusion. Therefore, proper clinical evaluation is required.
PubMed: 34471629
DOI: 10.1007/s12070-020-02331-9 -
Orphanet Journal of Rare Diseases Aug 2021Children with Robin sequence (RS) are at risk of growth failure, mainly due to their increased work of breathing and feeding difficulties. Various conservative and...
BACKGROUND
Children with Robin sequence (RS) are at risk of growth failure, mainly due to their increased work of breathing and feeding difficulties. Various conservative and surgical treatment approaches exist, but their impact on weight gain has not yet been adequately addressed. A functional treatment concept, used in our center for > 20 years, includes a pre-epiglottic baton plate (Tuebingen palatal plate) and intensive feeding training.
OBJECTIVE
To investigate the effect of the Tuebingen treatment protocol on growth and weight trajectories during infancy.
METHODS
This retrospective study analyzed longitudinal data from infants with isolated RS admitted to Tuebingen University Children's Hospital, Germany between 1998 and 2019. Through our electronic patient database, we evaluated anthropometric parameters until reaching 1-year follow-up. Results are shown as median (IQR).
RESULTS
In 307 infants analyzed, median Z-score for weight decreased from - 0.28 at birth to - 1.12 upon admission to our center at a median age of 22 days. Z-score then remained largely unchanged until discharge (Z-score difference, - 0.08), while the proportion of infants receiving tube feedings decreased from 55.1 to 13.7%. Z-score subsequently increased from - 1.17 at discharge to - 0.44 at the 1-year follow-up (p < 0.001).
CONCLUSION
Based on a comparatively large cohort, this functional treatment was associated with better weight gain and improved feeding. As RS infants often show postnatal growth failure, weight monitoring may be a valuable parameter for monitoring treatment effectiveness. Clinical Trial Registration Not necessary due to the retrospective design.
Topics: Child; Hospitalization; Humans; Infant; Infant, Newborn; Palate; Pierre Robin Syndrome; Retrospective Studies; Treatment Outcome
PubMed: 34344420
DOI: 10.1186/s13023-021-01959-2 -
Familial Cancer Oct 2023Pathogenic germline DICER1 variants are associated with pleuropulmonary blastoma, multinodular goiter, embryonal rhabdomyosarcoma and other tumour types, while mosaic...
Pathogenic germline DICER1 variants are associated with pleuropulmonary blastoma, multinodular goiter, embryonal rhabdomyosarcoma and other tumour types, while mosaic missense DICER1 variants in the RNase IIIb domain are linked to cause GLOW (global developmental delay, lung cysts, overgrowth, and Wilms' tumor) syndrome. Here, we report four families with germline DICER1 pathogenic variants in which one member in each family had a more complex phenotype, including skeletal findings, facial dysmorphism and developmental abnormalities. The developmental features occur with a variable expressivity and incomplete penetrance as also described for the neoplastic and dysplastic lesions associated with DICER1 variants. Whole exome sequencing (WES) was performed on all four cases and revealed no further pathogenic or likely pathogenic dominant, homozygous or compound heterozygous variants in three of them. Notably, a frameshift variant in ARID1B was detected in one patient explaining part of her phenotype. This series of patients shows that pathogenic DICER1 variants may be associated with a broader phenotypic spectrum than initially assumed, including predisposition to different tumours, skeletal findings, dysmorphism and developmental abnormalities, but genetic work up in syndromic patients should be comprehensive in order not to miss additional underlying /modifying causes.
Topics: Female; Humans; Germ-Line Mutation; Phenotype; Frameshift Mutation; Cysts; Ribonuclease III; Germ Cells; DEAD-box RNA Helicases
PubMed: 34331184
DOI: 10.1007/s10689-021-00271-z -
American Journal of Physiology. Cell... Sep 2021
Topics: Animals; Cell Differentiation; Cell Fusion; Disease Models, Animal; Humans; Membrane Fusion; Membrane Proteins; Mice; Mice, Knockout; Mobius Syndrome; Muscle Proteins; Muscular Diseases; Mutation, Missense; Myoblasts, Skeletal; Pierre Robin Syndrome; Protein Isoforms; Zebrafish
PubMed: 34288723
DOI: 10.1152/ajpcell.00187.2021