Palate Abnormalities Research Articles

Outcome of patients with complete cleft lip and alveolus: 20-year follow-up.

Patients with cleft have functional and aesthetic impairment, and typically require several interventions as they grow. Long-term evaluation following a treatment protocol is essential, but such reports on patients with complete cleft lip and alveolus (CLA) are sparse in the literature. A retrospective review was conducted to all patients with complete CLA born between January 1995 and August 2002 and treated at our center. Patients who received continuous multidisciplinary team care until 20 years of age were included, and patients with cleft palate and syndromic abnormalities were excluded. Facial bone growth was evaluated using cephalometric analysis. Eighty-seven and 11 patients with unilateral and bilateral CLA (UCLA and BCLA) were included respectively. All patients received one-stage cheiloplasty with primary rhinoplasty. Revisional lip/nose surgery was performed in 21.8 and 27.3% during growing age, and in 51.7 and 72.7% after skeletal maturity. Orthognathic surgery was performed in 20.7 and 27.3%. Compared with UCLA patients, BCLA had larger number of operations (3.0 versus 3.7, p = 0.03) and higher chance of receiving alveolar bone grafting twice (1.1% versus 36.4%, p < 0.01). Patients with complete CLA had less hypoplastic maxilla, and received smaller number of operations than complete cleft lip and palate. Complete CLA is a less severe form of cleft, but the patients still require multiple interventions. This review revealed certain suboptimal results, and modifications have been made in the treatment protocol. Longitudinal follow-up and periodic assessment help to establish an ideal therapeutic strategy and improve overall cleft care.

STAC3 disorder: a common cause of congenital hypotonia in Southern African patients.

STAC3 disorder, or Native American myopathy, is characterised by congenital myopathy, hypotonia, musculoskeletal and palatal anomalies, and susceptibility to malignant hyperthermia. A STAC3 c.851 G > C (p.Trp284Ser) pathogenic variant, common in the Lumbee Native American tribe, has been identified in other populations worldwide, including patients of African ancestry. We report on the frequency of STAC3 c.851 G > C in a cohort of 127 patients presenting with congenital hypotonia that tested negative for spinal muscular atrophy and/or Prader-Willi syndrome. We present a clinical retrospective, descriptive review on 31 Southern African patients homozygous for STAC3 c.851 G > C. The frequencies of various phenotypic characteristics were calculated. In total, 25/127 (20%) laboratory-based samples were homozygous for STAC3 c.851 G > C. A carrier rate of 1/56 and a predicted birth rate of 1/12 500 was estimated from a healthy cohort. A common haplotype spanning STAC3 was identified in four patients. Of the clinical group, 93% had a palatal abnormality, 52% a spinal anomaly, 59% had talipes equinovarus deformity/deformities, 38% had arthrogryposis multiplex congenita, and 22% had a history suggestive of malignant hyperthermia. The novel finding that STAC3 disorder is a common African myopathy has important clinical implications for the diagnosis, treatment and genetic counselling of individuals, with neonatal and/or childhood hypotonia with or without arthrogryposis multiplex congenita, and their families. The spread of this variant worldwide and the allele frequency higher in the African/African-American ancestry than the Admixed Americans, strongly indicates that the STAC3 c.851 G > C variant has an African origin which may be due to anancient mutation with migration and population bottlenecks.

Evaluation of the effect of palatoplasty on the quality of life and speech outcomes in patients with velocardiofacial syndrome.

Children diagnosed with velocardiofacial syndrome (VCFS) suffer from various disabilities. Palatal abnormalities, as well as speech and language impairment, adversely affect a child's quality of life (QoL) and are some of the most distressing aspects for the parents of these children. The present study aimed to explore the effect of palatoplasty on the health-related quality of life (HRQoL) and speech outcomes in children with VCFS. The study recruited 20 patients (N = 20) with VCFS and connected speech, aged 3 years or older, having either undiagnosed submucous cleft palate (SMCP) or velopharyngeal insufficiency (VPI), and requiring primary cleft palate surgery or revision surgery. Speech assessment was conducted prior to palatoplasty and 6 months after the surgery. Intelligibility and hypernasality were evaluated using the Cleft Audit Protocol for Speech - Augmented (CAPS-A). The parent proxy-report form of the Pediatric Quality of Life Inventory (PedsQL™) was used to evaluate and compare the HRQoL of the VCFS patients before and after palatoplasty. Significant improvement in the HRQoL scores was achieved after the surgery across all domains (physical, emotional, social, and school functioning), especially in the emotional and social dimensions (p < 0.000). The post-operative speech assessment based on CAPS-A demonstrated improvement in speech intelligibility and hypernasality in the majority of patients. Given that children with VCFS face various medical and social problems, suitable palatal interventions are beneficial, improving both the speech ability and QoL of these children.

Novel Genetic and Phenotypic Expansion in Ameliorated PUF60-Related Disorders.

Heterozygous variants in the Poly(U) Binding Splicing Factor 60kDa gene (PUF60) have been associated with Verheij syndrome, which has the key features of coloboma, short stature, skeletal abnormalities, developmental delay, palatal abnormalities, and congenital heart and kidney defects. Here, we report five novel patients from unrelated families with PUF60-related disorders exhibiting novel genetic and clinical findings with three truncating variants, one splice-site variant with likely reduced protein expression, and one missense variant. Protein modeling of the patient's missense variant in the PUF60 AlphaFold structure revealed a loss of polar bonds to the surrounding residues. Neurodevelopmental disorders were present in all patients, with variability in speech, motor, cognitive, social-emotional and behavioral features. Novel phenotypic expansions included movement disorders as well as immunological findings with recurrent respiratory, urinary and ear infections, atopic diseases, and skin abnormalities. We discuss the role of PUF60 in immunity with and without infection based on recent organismic and cellular studies. As our five patients showed less-severe phenotypes than classical Verheij syndrome, particularly with the absence of key features such as coloboma or palatal abnormalities, we propose a reclassification as PUF60-related neurodevelopmental disorders with multi-system involvement. These findings will aid in the genetic counseling of patients and families.

Choice of Surgeons in Retractors used in Cleft Lip and Palate Surgery: An Original Research.

To ensure optimal exposure and enable precise tissue manipulation, cleft lip and palate abnormalities require surgical repair utilizing retractors. Different retractors may affect surgical outcomes; however, this is not yet evident. Examining surgeon preferences for retractors in cleft lip and palate surgery and assessing their impact on patient outcomes were the goals of this study. The patients who underwent primary cleft lip and palate repair were retrospectively analyzed. This study evaluated three widely used retractors: the Langenbeck, Gelpi, and Moult Mouth Gag retractors. This study looked at demographic information, surgical results (including scarring, aesthetic outcomes, and wound healing issues), and surgeon preferences for retractors. The study identified differences in surgical outcomes related to various retractor types. Both Group A (Langenbeck retractor) and Group B (Gelpi retractor) demonstrated similar favorable results, such as little wound healing issues, less scarring, and pleasing cosmetic results. The wound healing issues, scarring, and cosmetic outcomes were all worse in Group C (Moult Mouth Gag retractor). Retractors were not always preferred by surgeons doing cleft lip and palate surgery. The type of retractor had an impact on the surgical results; the Moult Mouth Gag retractor performed less well than the Langenbeck and Gelpi retractors. These results highlight the value of using evidence-based criteria to select retractors more effectively and enhance surgical methods for better patient outcomes in cleft lip and palate repair.

Endoscopic septoplasty below the age of 17 years

BackgroundThe claim that septoplasty in children should not be done was raised in the early last century. Pediatric septoplasty is highly controversial. Some surgeons are concerned that early surgical intervention before age 17 can adversely affect the normal growth of the nose and face. On the contrary, there is evidence of significant dental, palatal, and facial abnormalities following traumatic damage to the septal cartilage. Therefore, surgical correction of the deviated nasal septum may be performed regardless of the patient’s age. The recommendation of early surgery is based on the explanation that the earlier the correction of septal deviation, the better the outcome of developing normal breath and acceptable facial growth. This study evaluates the nasal and facial bony growth after endoscopic septoplasty for patients below the age of 17 years.MethodsThis retrospective study reviewed 39 patients who underwent endoscopic septoplasty. The involved patients’ age at surgery was below 17 years old. Postoperative evaluation was done for all patients subjectively using the visual analog scale (VAS) and objectively by endoscopic nose examination. The nasal and facial bony growth were evaluated using lateral cephalometry, which was carried out for each patient when they reached the age of 17.ResultsThirty-nine patients underwent endoscopic septoplasty. The median visual analog scale for nose block and headache significantly declined after the procedure significant differences were observed between patients and controls regarding the following parameters: palatal length, anterior skull base, mid-face protrusion, and mid-face length.ConclusionEarly endoscopic septoplasty below the age of 17 is a safe procedure and does not compromise the nasal or facial growth when indicated for patients with severe persistent nose block and poor quality of life.

THE EFFECT OF PREVENTIVE MEASURES ON THE PROPERTIES OF ORAL FLUID IN CHILDREN AFTER RADICAL URANOPLASTY

Introduction. Among the causes of many functional disorders in cleft palate abnormalities there are imperfections of the anatomical structures of the upper jaw, formed at the stage of facial embryogenesis. Inadequate capacity of protective mechanisms in the oral cavity is manifested by a decrease in the proper functioning of the major and minor salivary glands and changes in the level of biologically active components in the oral fluid that are responsible for maintaining homeostasis, which requires a certain correction.&#x0D; Purpose of this study is to assess the effectiveness of the treatment and preventive measures after radical uranoplasty. Materials and Methods. 23 children aged 4 to 6 years with congenital cleft palate were involved in the study. Salivation rate, physicochemical and biochemical properties of the oral fluid were studied one month after surgery and after the completion of the monthly treatment course and receiving preventive measures.&#x0D; Results. The study has shown a decrease in salivation rate, pH level, and activity of α-amylase in oral fluid compared to the control group. Bilateral cleft defects showed more significant changes in the parameters. After one month of treatment and preventive measures, the salivation rate increased, and the physicochemical and biochemical properties of oral fluid improved. However, all values did not reach the control values, indicating the need for periodic repeated courses of treatment and prevention.&#x0D; Conclusion. Children with congenital cleft palate demonstrate decreased functioning of salivary glands that leads to a deterioration of the mechanical and chemical self-cleaning of the oral cavity. Changes in the physicochemical and biochemical properties of oral fluid disrupt its physiological balance thus, contributing to a deterioration of pH level and metabolic processes. Repeated treatment courses are necessary to maintain proper conditions for the mineralizing potential of oral fluid.

Spondyloepipheseal dysplasia tarda

Skeletal disorders are common entities that we encounter in our daily practice. Their early diagnosis is key to proper management and genetic counselling. Spondyloepiphyseal dysplasia is one such disorder. It is a genetic bone deformity that affects the spine, proximal epiphysis and pelvis. The disease is either manifested at birth or during adolescence therefore given the terms SED congenita or SED tarda. Patients with SED present with variable features including short height, short neck, club foot, cleft palate, kyphoscoliosis or lordotic abnormalities. We also present a case of an 11-year-old boy who presented to us with complaints of stunted growth and abnormal posture and underwent radiological imaging.

Unique Considerations in the Treatment of Psychosis in DiGeorge Syndrome: A Case Report

AbstractIntroductionDiGeorge Syndrome is a microdeletion of chromosome 22q11.2 and is most commonly de novo. Manifestations of DiGeorge are wide-spread including cardiac malformations, palatal abnormalities, intellectual disability, hypocalcemia, dysmorphic facial features, and psychiatric disorders (psychotic disorders, Autism, ADHD, etc). This case report highlights difficulties with diagnosis and treatment of psychosis in DiGeorge. This 29 yo male with history of DiGeorge and associated cardiac anomalies presented to the outpatient clinic with prior diagnoses of schizoaffective disorder, bipolar disorder, DMDD, autism, and ADHD. Patient denied all symptoms, though mother noted hallucinations for 5–6 years. He was previously on aripiprazole and divalproex and developed a resting tremor. With family history of Parkinson’s disease (PD), increased risk of PD in DiGeorge, and no improvement in tremor with dose reduction of aripiprazole or discontinuation of divalproex, neurology diagnosed PD, which was later negated when tremor resolved with complete discontinuation of aripiprazole. In our clinic we slowly increased divalproex and olanzapine, though parent concern of sedation limited higher doses. Patient had moderate improvement in symptoms per parents, but after several months on moderate-dose olanzapine, he developed a tremor. Sensitivity to extrapyramidal symptoms limits medication selection. Furthermore, QT prolongation in a population with cardiac abnormalities poses a unique risk. Given complexity and poor response, we researched pathogenesis and treatment of psychosis in DiGeorge.MethodsWe reviewed literature on PubMed with keywords including “DiGeorge,” “treatment,” “psychosis.” Specifically, we looked at articles addressing treatment response, efficacy, side effects, novel treatments, and the pathogenesis as it relates to treatment.ResultsLiterature indicates that psychotic symptoms are more treatment resistant compared to psychotic disorders not associated with DiGeorge and there is little consensus on which antipsychotics are more effective. The 22q11.2 deletion contains the gene segment for catechol-O-methyltransferase (COMT) and the resulting COMT deficiency leads to excess catecholamines. The presence of the low activity COMT variant on the remaining allele is associated with possibly more severe psychiatric symptoms. Metyrosine may be a potential medication in the treatment of psychosis in DiGeorge by interfering with dopamine synthesis. Overall there is sparse research on treatment of psychosis in DiGeorge and a lack of firm recommendations.ConclusionThis case study exemplifies the need for further research on DiGeorge Syndrome and treatment of psychosis. Treatment is complicated by cardiac abnormalities, comorbid neuropsychiatric conditions confounding diagnosis, and little research on treatments that target the unique pathogenesis. Research is inconsistent concerning recommendations and novel treatments are primarily anecdotal.FundingNo Funding

Further characterization of the 9q31 microdeletion phenotype; delineation of a common region of overlap containing ZNF462.

Loss of function variants and whole gene deletions of ZNF462 has been associated with a novel phenotype of developmental delay/intellectual disability and distinctive facial features. Over two dozen cases have been reported to date and the condition is now known as Weiss-Kruszka syndrome (OMIM# 618619). There are several older reports in the literature and DECIPER detailing individuals with interstitial deletions of 9q31 involving the ZNF462 gene. Many of the characteristic facial features described in these microdeletion cases are similar to those who have been diagnosed with Weiss-Kruszka syndrome. We describe three additional patients with overlapping 9q31 deletions and compare the phenotypes of the microdeletion cases reported in the literature to Weiss-Kruszka syndrome. Phenotypic overlap was observed between patients with 9q31 deletions and Weiss-Kruszka syndrome. Several additional features were noted in 9q31 deletion patients, including hearing loss, small head circumference, palate abnormalities and short stature. The common region of overlap of microdeletion cases implicates ZNF462 as the main driver of the recognizable 9q31 microdeletion phenotype. The observation of additional features in patients with 9q31 microdeletions that are not reported in Weiss-Kruszka syndrome further suggests that other genes from the 9q31 region likely act synergistically with ZNF462 to affect phenotypic expression.

130 Surgical Repair of Cleft Lip: Comparison of Neonatal and Standard Time Repair

Abstract Aim Cleft lip and palate (CLP) abnormalities are the most common congenital orofacial anomalies, affecting 1 in 700 live births per year in the United Kingdom. Cleft lip is present in approximately 55% of all CLP deformities. The aim of this study is to compare standard and neonatal cleft lip repair. Method Advanced literature searches were carried out using Medline ALL (1946 to date) and Embase (1974 to date), 11 articles were deemed relevant and included in this study. Results Aesthetic results showed excellent outcomes with neonatal repair with regards to the appearance of the scar, facial (lip and nasal) symmetry but those aesthetic results are no better than those achieved at standard time. Conclusions Early intervention can be beneficial as early repair takes place when the cleft is less severe and when the tissues are more malleable, making the surgery less challenging and when some aspects of foetal scar healing remain. Early repair has a positive impact on the development of the alveolar projections and can assist in reducing an alveolar cleft if present, improving the aesthetic outcome. Neonatal surgery carries with it no greater risk than surgery carried out at 6 months and will allow feeding to begin at an early stage promoting recovery. Early repair also brings with it a positive psychosocial impact where infants and mothers can build a normal relationship from an early stage. Later in life, children and adults will be less self-conscious following good aesthetic repair. In conclusion, neonatal repair may be recommended over standard time repair.

Genipin treatment of equine palatal dysfunction: A preliminary study of safety and efficacy

SummaryBackgroundPalatal dysfunction is a common cause of poor performance in racehorses. Although conservative management resolves just over 60% of cases, there is a requirement for further intervention in the residual 40% of cases that do not respond. It is proposed that a palatal stiffening technique that is simple to perform, safe, minimally invasive and enables a rapid return to exercise would be an acceptable first intervention. Genipin is a self‐polymerising molecule that bonds to collagen matrices increasing tissue strength, stiffness and resilience. A previous study demonstrated that implanted genipin increased palatal strength and its resistance to deformation and potentially was effective in decreasing likelihood of palatal dysfunction in horses.ObjectivesThe objective of the study was to appraise the safety and feasibility of implanting genipin oligomers into the equine soft palate and to report on racehorse trainers' subjective assessment of its usefulness in management of palatal dysfunction.Study designProspective, non‐randomised, pilot study.MethodsFifty Thoroughbred racehorses diagnosed with palatal dysfunction were implanted transendoscopically with genipin. The horses were monitored for adverse reactions during hospitalisation. A standard questionnaire provided to the horses' trainers was used to record additional adverse reactions and satisfaction with the animals' subsequent performance. Post‐treatment dynamic endoscopy was performed in a subgroup of animals.ResultsOne horse developed adverse clinical signs of pyrexia and reduced appetite, which responded to treatment. Post‐procedural endoscopic examination revealed mild palatal abnormalities in 6 of 50 horses that showed no clinical signs. One horse had mild generalised oedema, four with mild focal swelling and one with a superficial mucosal ulceration at a single site of implantation of the soft palate. Following treatment, 76% of horses were reported to show clinical improvement by their trainers with 24% reported not to show improvement.Main limitationsThe study was not controlled, and outcome measures were mainly subjective.ConclusionsThe procedure was well tolerated, safe, minimally invasive and enabled a rapid return to exercise. Trainer reported improvement was comparable to previously reported palatoplasty procedures.

Natural history of KBG syndrome in a large European cohort.

KBG syndrome (KBGS) is characterized by distinctive facial gestalt, short stature and variable clinical findings. With ageing, some features become more recognizable, allowing a differential diagnosis. We aimed to better characterize natural history of KBGS. In the context of a European collaborative study, we collected the largest cohort of KBGS patients (49). A combined array- based Comparative Genomic Hybridization and next generation sequencing (NGS) approach investigated both genomic Copy Number Variants and SNVs. Intellectual disability (ID) (82%) ranged from mild to moderate with severe ID identified in two patients. Epilepsy was present in 26.5%. Short stature was consistent over time, while occipitofrontal circumference (median value: -0.88 SD at birth) normalized over years. Cerebral anomalies, were identified in 56% of patients and thus represented the second most relevant clinical feature reinforcing clinical suspicion in the paediatric age when short stature and vertebral/dental anomalies are vague. Macrodontia, oligodontia and dental agenesis (53%) were almost as frequent as skeletal anomalies, such as brachydactyly, short fifth finger, fifth finger clinodactyly, pectus excavatum/carinatum, delayed bone age. In 28.5% of individuals, prenatal ultrasound anomalies were reported. Except for three splicing variants, leading to a premature termination, variants were almost all frameshift. Our results, broadening the spectrum of KBGS phenotype progression, provide useful tools to facilitate differential diagnosis and improve clinical management. We suggest to consider a wider range of dental anomalies before excluding diagnosis and to perform a careful odontoiatric/ear-nose-throat (ENT) evaluation in order to look for even submucosal palate cleft given the high percentage of palate abnormalities. NGS approaches, following evidence of antenatal ultrasound anomalies, should include ANKRD11.

Gastrointestinal Features of 22q11.2 Deletion Syndrome Include Chronic Motility Problems From Childhood to Adulthood.

22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion syndrome and has a multisystemic presentation including gastrointestinal features that have not yet been fully described. Our aim was to examine lifetime gastrointestinal problems in a large cohort of patients with 22q11.2DS. All patients followed in the 22q and You Center at the Children's Hospital of Philadelphia (n = 1421) were retrospectively screened for: 1) age ≥ 17 years, 2) documented chromosomal microdeletion within the 22q11.2 LCR22A-LCR22D region, and 3) sufficient clinical data to characterize the adult gastrointestinal phenotype. Gastrointestinal problems in childhood, adolescence, and adulthood were summarized. Statistical association testing of symptoms against other patient characteristics was performed. Included patients (n = 206; 46% female; mean age, 27 years; median follow-up, 21 years) had similar clinical characteristics to the overall cohort. Genetic distribution was also similar, with 96% having deletions including the critical LCR22A-LCR22B segment (95% in the overall cohort). Most patients experienced chronic gastrointestinal symptoms in their lifetime (91%), but congenital gastrointestinal malformations (3.5%) and gastrointestinal autoimmune diseases (1.5%) were uncommon. Chronic symptoms without anatomic or pathologic abnormalities represented the vast burden of illness. Chronic symptoms in adulthood are associated with other chronic gastrointestinal symptoms and psychiatric comorbidities ( P < 0.01) but not with deletion size or physiologic comorbidities ( P > 0.05). One exception was increased nausea/vomiting in hypothyroidism ( P = 0.002). Functional gastrointestinal disorders (FGIDs) are a common cause of ill health in children and adults with 22q11.2DS. Providers should consider screening for the deletion in patients presenting with FGIDs and associated comorbidities such as neuropsychiatric illness, congenital heart disease, and palatal abnormalities.

Morphological Abnormalities in Schizophrenia: Systematic Review

Schizophrenia is a severe, frequent, heterogeneous, longlasting and disabling chronic mental illness with high social impact, belonging to the group of chronic psychoses. There are several clinical forms and several possible evolutionary modes. Its etiopathogenesis is multifactorial (hereditary, biological, environmental, etc.) but no single cause has been demonstrated up till now. Schizophrenia is a group of disabling heterogeneous disorders that are generally severe, the course of which is chronic and disabling, and the prognosis is poor. Many retrospective studies have attempted to trace the premorbid history of adult subjects who developed schizophrenia. Their results appear to be extremely disparate, due in particular to the heterogeneity of the means of investigation used. In addition, in recent years, many studies have focused on prodromal symptoms occurring during the year preceding the first psychotic episode in late adolescence or early adulthood. Minor physical cranio-cerebral (at the level of the ears, the palate, the cranial perimeter), temporomandibular, dental and palatal abnormalities, dermatoglyphic disturbances or even subtle neurological signs have been frequently found in schizophrenic patients, in particular oral anomalies, more precisely the measurements of the teeth, their vestibulo-lingual and mesio-distal diameters. The objective of our article is to study the morphological abnormalities that exist in the patient with schizophrenia, and to demonstrate whether there is a link between the presence of these physical abnormalities and the occurrence of schizophrenia. This issue has been vaguely mentioned in the literature, but in the Moroccan context, it is a pilot study.

Phenotypic expansion and variable expressivity in individuals with JARID2-related intellectual disability: A case series.

Loss of function variants in JARID2 were recently reported in 16 patients with a neurodevelopmental disorder characterized by delays, intellectual and learning disability, autism, behavioral abnormalities, and dysmorphic features. Most cases were de novo, with only one variant inherited from an affected parent. Here, we present seven additional individuals from five families with pathogenic or likely pathogenic JARID2 variants, confirming this gene-disease association and highlighting palatal abnormalities and heart defects as part of the phenotype. In addition, we report inheritance of JARID2 variants from mildly affected parents, demonstrating the variable expressivity of the disease. We also note the high prevalence of intragenic JARID2 copy number variants, emphasizing the importance of exon-level analysis.

Re-thinking lactation-related nipple pain and damage.

Nipple pain is a common reason for premature cessation of breastfeeding. Despite the benefits of breastfeeding for both infant and mother, clinical support for problems such as maternal nipple pain remains a research frontier. Maternal pharmaceutical treatments, and infant surgery and bodywork interventions are commonly recommended for lactation-related nipple pain without evidence of benefit. The pain is frequently attributed to mammary dysbiosis, candidiasis, or infant anatomic anomaly (including to diagnoses of posterior or upper lip-tie, high palate, retrognathia, or subtle cranial nerve abnormalities). Although clinical protocols universally state that improved fit and hold is the mainstay of treatment of nipple pain and wounds, the biomechanical parameters of pain-free fit and hold remain an omitted variable bias in almost all clinical breastfeeding research. This article reviews the research literature concerning aetiology, classification, prevention, and management of lactation-related nipple–areolar complex (NAC) pain and damage. Evolutionary and complex systems perspectives are applied to develop a narrative synthesis of the heterogeneous and interdisciplinary evidence elucidating nipple pain in breastfeeding women. Lactation-related nipple pain is most commonly a symptom of inflammation due to repetitive application of excessive mechanical stretching and deformational forces to nipple epidermis, dermis and stroma during milk removal. Keratinocytes lock together when mechanical forces exceed desmosome yield points, but if mechanical loads continue to increase, desmosomes may rupture, resulting in inflammation and epithelial fracture. Mechanical stretching and deformation forces may cause stromal micro-haemorrhage and inflammation. Although the environment of the skin of the nipple–areolar complex is uniquely conducive to wound healing, it is also uniquely exposed to environmental risks. The two key factors that both prevent and treat nipple pain and inflammation are, first, elimination of conflicting vectors of force during suckling or mechanical milk removal, and second, elimination of overhydration of the epithelium which risks moisture-associated skin damage. There is urgent need for evaluation of evidence-based interventions for the elimination of conflicting intra-oral vectors of force during suckling.

Non-balanced translocation between the short arms of chromosomes 8 and 6 associated with type 1 diabetes mellitus.

SummaryWe describe a rare case of a girl with an initial diagnostic hypothesis of chromosome 8 trisomy based on clinical findings and karyotyping, which identified a structural change in the short arm of chromosome 8 (46,XX,add(8)(p23)). At the age of 7, she developed type 1 diabetes mellitus and started insulin therapy with multiple daily doses, and then she started to use a continuous insulin infusion system (pump) at 10 years of age. At the age of 12, she underwent a molecular study that identified an unbalanced translocation between the short arms of chromosomes 6 and 8 – 46,XX,add(8)(p23).ish der(8)t(6;8)(GS-196I5+;RP-11338B22−).Learning pointsPatients with an unbalanced translocation between the short arms of chromosomes 6 and 8 – 46,XX,add(8)(p23).ish der(8)t(6;8)(GS-196I5+;RP-11338B22-) may present syndromic features suggestive of chromosome 8 trisomy.Main characteristics are a prominent forehead, ocular and breast hypertelorism, ocular, external ear and palate abnormalities, a short neck, heart defects, and developmental delay.Patients with 46,XX,add(8)(p23).ish der(8)t(6;8)(GS-196I5+;RP-11338B22-) may present autoimmune type 1 diabetes mellitus.Karyotyping is an essential tool for the diagnosis of chromosomal changes, but it has some limitations.Multiplex ligation-dependent probe amplification, array-single nucleotide polymorphism and fluorescence in situ hybridization can help diagnose genetic syndromes in patients with atypical evolution.

An Extremely Rare Case of Birk-Barel Syndrome With Severe Central Apneas

Birk-Barel syndrome, alternatively known as KCNK9 imprinting syndrome, is caused by a missense mutation in the potassium two pore domain channel subfamily K member 9 (KCNK9) gene on chromosome 8q24.3. This syndrome demonstrates dominant inheritance and is imprinted with paternal silencing, where the paternally inherited allele is silenced, and the maternally inherited allele is active. Congenital hypotonia, palatal abnormalities, intellectual disability, severe feeding difficulties, and dysmorphic facial features characterize this sporadic genetic syndrome. To date, there are approximately 21 molecularly diagnosed individuals worldwide described in the literature. We describe the first known case of Puerto Rican ethnicity, a 16-month-old female born prematurely at 36-weeks with Birk-Barel syndrome, confirmed with whole-exome sequencing, and her response to non-invasive ventilation as a treatment for her sleep breathing disorder.

Congenital Nasal Pyriform Aperture Stenosis: Evidence of Premature Fusion of the Midline Palatal Suture

Various etiologies have been theorized for the development of congenital nasal pyriform aperture stenosis (CNPAS). Imaging possibly implicates abnormal fusion of the midline palatal suture and deficient lateral growth of the midface in affected neonates. A single-center, retrospective study was performed at a tertiary care pediatric hospital involving neonates and infants between 0 and 90 days of life. Maxillofacial CT scans of patients were reviewed. Abnormality of the palatal suture and midface transverse dimensions were measured and analyzed in patients with and without CNPAS. A total of 109 patients between 0 and 90 days of life had maxillofacial CT scans. Thirteen patients were classified as having CNPAS, 27 patients had normal scans (control group), and 69 patients were excluded because of the presence of other craniofacial anomalies. All patients with CNPAS had evidence of abnormal fusion of the midline palatal suture. Zero patients without CNPAS had a midline palatal suture abnormality. The mean widths of the pyriform aperture were 5.7 mm (SD, 1.7) in the CNPAS group and 13.1 mm (SD, 2.7) in the control group (P < .0001). The mean distance between the superior portions of the nasolacrimal ducts was 9.1 mm (SD, 2.1) in the CNPAS group, and the mean of the control group was 13.4 mm (SD, 2.2) (P < .0001). Patients with CNPAS have abnormal fusion of the midline palatal suture and exhibit lateral growth restriction of the midface. This may implicate synostosis of the midline palatal suture and abnormal midface growth.