Congenital Research Articles

Postpartumzorg in de eerste lijn: samenvatting van een multidisciplinaire richtlijn (deel 1)

Postpartum care in primary care: summary of a multidisciplinary guideline The lying time at the maternity ward for a healthy woman giving birth to a healthy baby is now on average less than 3 days. Therefore, primary care providers have a greater responsibility in the follow-up of the mother and newborn during the postpartum period. This article is a summary of the first part of the multidisciplinary guideline Postpartum care in primary care developed by the national Working Group Development of Primary Care Guidelines (WOREL) according to the internationally recognised methods of guideline development. The guideline formulates recommendations for quality postpartum care in collaboration with all involved healthcare providers with the aim of recognising and addressing complications in the newborn and mother in a timely manner. It is important that healthcare providers know what is normal, which red flags they should not miss, have basic knowledge about conditions and situations, and timely refer the patient to primary or secondary care. The article describes what attitude to adopt in case of life-threatening and serious complications in the maternity woman (postpartum haemorrhage, pre-eclampsia, venous thromboembolism and endometritis) and the newborn (jaundice, neonatal sepsis, congenital heart defect, dehydration, nutritional difficulties and metabolic disorders), as well as in case of less severe complications or complaints in the maternity woman (perineal pain, headache, constipation, haemorrhoids, urinary incontinence, fatigue and back pain) and the baby (gastro-oesophageal reflux, thrush, nappy dermatitis, intestinal cramps, conjunctivitis, cord infections and fever). Finally, specific situations in both the mother (prevention of antibody formation, rubella vaccination, thyroid disorders and gestational diabetes) and the newborn (cord care, prevention of sudden death, vitamin K and vitamin D substitution, and child abuse) are highlighted.

Functional and Genetic Analyses Unveil the Implication of CDC27 in Hemifacial Microsomia.

Hemifacial microsomia (HFM) is a rare congenital genetic syndrome primarily affecting the first and second pharyngeal arches, leading to defects in the mandible, external ear, and middle ear. The pathogenic genes remain largely unidentified. Whole-exome sequencing (WES) was conducted on 12 HFM probands and their unaffected biological parents. Predictive structural analysis of the target gene was conducted using PSIPRED (v3.3) and SWISS-MODEL, while STRING facilitated protein-to-protein interaction predictions. CRISPR/Cas9 was applied for gene knockout in zebrafish. In situ hybridization (ISH) was employed to examine the spatiotemporal expression of the target gene and neural crest cell (NCC) markers. Immunofluorescence with PH3 and TUNEL assays were used to assess cell proliferation and apoptosis. RNA sequencing was performed on mutant and control embryos, with rescue experiments involving target mRNA injections and specific gene knockouts. CDC27 was identified as a novel candidate gene for HFM, with four nonsynonymous de novo variants detected in three unrelated probands. Structural predictions indicated significant alterations in the secondary and tertiary structures of CDC27. cdc27 knockout in zebrafish resulted in craniofacial malformation, spine deformity, and cardiac edema, mirroring typical HFM phenotypes. Abnormalities in somatic cell apoptosis, reduced NCC proliferation in pharyngeal arches, and chondrocyte differentiation issues were observed in cdc27-/- mutants. cdc27 mRNA injections and cdkn1a or tp53 knockout significantly rescued pharyngeal arch cartilage dysplasia, while sox9a mRNA administration partially restored the defective phenotypes. Our findings suggest a functional link between CDC27 and HFM, primarily through the inhibition of CNCC proliferation and disruption of pharyngeal chondrocyte differentiation.

Durable cellular immune response against inactivated ZIKV and envelope proteins in ZIKV-infected women during pregnancy

IntroductionZika virus (ZIKV) infection has been associated to Guillain-Barré syndrome in adults and congenital malformations during pregnancy, leading to the manifestation of congenital Zika syndrome (CZS). The ZIKV envelope protein (EZIKV), prominently displayed on the virus surface, is a primary target for the humoral immune response. However, limited information exists regarding its capacity to induce cellular immunity, particularly in pregnant women with a history of ZIKV infection. The EZIKV protein comprises three domains: the central domain (EDI), a dimerization domain (EDII), and a domain responsible for binding to the cell surface receptor (EDIII). To examine the regions of EZIKV targeted by cellular immunity, we examined cellular immune responses in a cohort of mothers infected with ZIKV, whose infants exhibited microcephaly.MethodsTo assess the ZIKV-specific response, we used inactivated virus and different recombinant viral envelope proteins (EZIKV, EDI/IIZIKV and EDIIIZIKV). All women in the study contracted the infection during pregnancy, with 72% experiencing symptoms such as fever, rash, joint pain, and retro-orbital pain. Peripheral blood mononuclear cells (PMBC) were collected post- ZIKV diagnosis confirmation, with a median time of 18 months (IQR 13.5-19) after parturition. Using the ELISpot assay, we quantified specific interferon-gamma (IFNγ) producing cells by stimulating PBMC with either inactivated ZIKV particles or equimolar amounts of recombinant EZIKV, EDI/IIZIKV and EDIIIZIKV.Results and discussionOur findings demonstrate the induction of IFN-γ producing cells in PBMC from ZIKV-convalescent mothers, whose infants manifested microcephaly, upon stimulation with both inactivated ZIKV particles and recombinant proteins. The identification of immunodominant regions within ZIKV can contribute for the development of targeted treatments and vaccine candidates tailored for pregnant women.

Pregnancy in Patients with the Fontan Operation.

Improved survival rates for patients with a Fontan circulation has allowed more women with this complex cardiac physiology to contemplate pregnancy. However, pregnancy in women with a Fontan circulation is associated with a high risk of adverse maternal and fetal outcomes, high rates of miscarriage and preterm delivery. Factors associated with a successful pregnancy outcome are: younger age, normal body weight, absence of significant functional limitation, no Fontan-related complications, and well-functioning single ventricle physiology. Appropriate care with timely preconception counselling and regular, frequent clinical reviews by a multidisciplinary team based at a tertiary centre, improves the chance of a successful pregnancy. Empowerment of patients with education on their specific congenital cardiac condition and its projected trajectory, helps them make informed choices regarding their health, reproductive choices and assists them to achieve their life goals.

Syndromic ciliopathy: a taiwanese single-center study

BackgroundSyndromic ciliopathies are a group of congenital disorders characterized by broad clinical and genetic overlap, including obesity, visual problems, skeletal anomalies, mental retardation, and renal diseases. The hallmark of the pathophysiology among these disorders is defective ciliary functions or formation. Many different genes have been implicated in the pathogenesis of these diseases, but some patients still remain unclear about their genotypes.MethodsThe aim of this study was to identify the genetic causes in patients with syndromic ciliopathy. Patients suspected of or meeting clinical diagnostic criteria for any type of syndromic ciliopathy were recruited at a single diagnostic medical center in Southern Taiwan. Whole exome sequencing (WES) was employed to identify their genotypes and elucidate the mutation spectrum in Taiwanese patients with syndromic ciliopathy. Clinical information was collected at the time of patient enrollment.ResultsA total of 14 cases were molecularly diagnosed with syndromic ciliopathy. Among these cases, 10 had Bardet-Biedl syndrome (BBS), comprising eight BBS2 patients and two BBS7 patients. Additionally, two cases were diagnosed with Alström syndrome, one with Oral-facial-digital syndrome type 14, and another with Joubert syndrome type 10. A total of 4 novel variants were identified. A recurrent splice site mutation, BBS2: c.534 + 1G > T, was present in all eight BBS2 patients, suggesting a founder effect. One BBS2 patient with homozygous c.534 + 1G > T mutations carried a third ciliopathic allele, TTC21B: c.264_267dupTAGA, a nonsense mutation resulting in a premature stop codon and protein truncation.ConclusionsWhole exome sequencing (WES) assists in identifying molecular pathogenic variants in ciliopathic patients, as well as the genetic hotspot mutations in specific populations. It should be considered as the first-line genetic testing for heterogeneous disorders characterized by the involvement of multiple genes and diverse clinical manifestations.

Rehabilitation of mandibular resected patients using fixed immediately loaded corticobasal implant -supported prostheses. A case series

Introduction and importanceAliments such as congenital conditions, pathological, and iatrogenic circumstances may result in mandibular defects that can severely disturb the patients' oral health, functions (mastication, speech), aesthetics, and quality of life and present a rehabilitating challenge. Case presentationwe present a multidisciplinary treatment approach for three cases presented with mandibular resection as a consequence of cystic, benign, and malignant tumour eradication that were rehabilitated with immediately loaded fixed corticobasal implant-supported prostheses and a follow-up period of 5,5 and 4 years.The reported cases present with excellent implant survival, along with healthy peri-implant tissues, stable prostheses, enhanced speech, chewing ability, aesthetics, superior patient satisfaction, and improved overall self-esteem. Clinical discussionA multidisciplinary oral and maxillofacial team is mandatory for the successful rehabilitation of patients with mandibular resection and to restore soft and hard tissue loss. The reported treatment modality offers the patient immediate fixed implant-supported prostheses omitting the need for a bone grafting procedure, with optimum peri-implant tissue health, excellent biomechanical and prosthetic results, and significant improvement in function and satisfaction. ConclusionCorticobasal fixed implant-supported prostheses can be a reliable treatment modality for mandibular resection, resulting in notable enhancements in the patients' oral health, appearance, mastication, speech, and self-esteem.

Klippel-Trénaunay Syndrome and Angiokeratoma: Case Report of a Rare Condition

Introduction: Klippel-Trénaunay syndrome is a rare congenital vascular disorder characterized by a triad of cutaneous capillary malformations, varicosities and hypertrophy of soft tissues and overgrowth bones. Among the cutaneous malformations are angiokeratomas, which appear as a papule from 2 to 10 mm in diameter, usually dark red in color, although they may be blue or black, and their surface is keratotic on palpation. Angiokeratomas pose a therapeutic challenge, especially in cases of multiple or extensive lesions. Laser modalities have demonstrated efficacy and may be successful treatment options. Clinical Case: A 13-year-old male patient with a clinical history of Klippel-Trénaunay syndrome diagnosed at birth. He came to the outpatient services because he presented dermal nodular lesions at the inguinal region, painful on palpation, with a duration of one week. In addition, he had an increase in diameter of the left lower limb with multiple varicose veins, ochre dermatitis on the inner side of his left leg. On the right lower limb there are violaceous patches with the presence of euchromic papules grouped together, of hard consistency at the left knee region. He also presents multiple violaceous keratotic papules on the scrotum, thigh and left knee bleeding on manipulation and trauma. Skin excision was performed in the right inguinal region for biopsy, which reported macroscopically fibrous, multinodular element measuring 0.7x0.5x0.3cm, whitish surface of firm consistency and whitish heterogeneous surface upon sectioning. Microscopic inspection was carried out with hematoxylin and eosin technique, which reported skin with epidermis showing acanthosis, hyperkeratosis, papillary dermis with congestive dilated vessels, negative for malignancy and compatible with angiokeratoma. Among the treatment options, it was decided to initiate CO2 laser therapy with satisfactory results. Conclusions: Klippel-Trénaunay syndrome is an extremely rare vascular pathology ........

Cornelia de Lange syndrome type 4 with a novel heterozygous missense variant in RAD 21 gene

Cornelia de Lange syndrome (CdLS) is a congenital multisystemic disorder characterized by genetic heterogeneity. It presents with features such as growth and cognitive retardation, upper limb deformities, cardiac, ophthalmologic, and genitourinary anomalies, alongside distinctive facial characteristics. The CdLS phenotype represents a spectrum that includes both classic and non-classic phenotypes resulting from pathogenic variants in genes associated with cohesin functioning, including NIBPL, SMC1A, SMC3, RAD21, BRD4, HDAC8, and ANKRD11. Mutations in these genes manifest diverse clinical features, with RAD21 variants accounting for a small percentage of cohesinopathies in humans. RAD21-related cohesinopathy typically exhibits growth retardation, minor skeletal anomalies, and facial features overlapping with CdLS. However, cognitive involvement tends to be milder. Despite this, due to the limited number of reported cases with RAD21 mutations, establishing genotype-phenotype correlations remain challenging. We present the case of an 18-month-old boy exhibiting developmental delay and distinct morphological features including micro-brachycephaly, depressed nasal bridge, upturned nose, long philtrum, low-set ears, mesomelic limb dwarfism, and a complete endocardial cushion defect. Exome sequencing revealed a novel RAD21 variant in this individual.

Literature Review: The Role of RET Gene Mutations in The Emergence of Hirschsprung Disease

Hirschsprung’s disease is a congenital condition characterized by a failure of nerve function along the gastrointestinal (GI) tract, resulting in the absence of enteric ganglia in the most distal segment of the colon. Although the prevalence rate is 1:5000 babies born, Hirschsprung’s disease can have a significant impact on patients, especially in terms of quality of life. One of the main genetic factors often associated with the etiopathogenesis of Hirschsprung’s disease is the RET gene. This study aims to provide scientific insight into advances in the understanding of genetic variants associated with RET gene mutations and their role in causing Hirschsprung disease. The research design used was literature review, articles were collected based on sources derived from Google Scholar, PubMed, and EMBASE which included national and international journals published in the last 10 years. Based on the articles collected, it was found that the RET gene is essential for the growth, migration, and maturation of precursor cells into functional neurons. Mutations in the RET gene can interfere with the normal formation and function of nerve cells, leading to symptoms typical of Hirschsprung’s disease.

Continuous epileptiform discharges are associated with worse neurodevelopmental findings in a congenital Zika syndrome prospective cohort

PurposeThis study aimed to identify continuous epileptiform discharges (CEDs) on electroencephalograms (EEG) and to determine their clinical significance in children with congenital Zika syndrome (CZS). MethodsThis prospective cohort study included 75 children diagnosed with CZS born from March 2015 and followed up until September 2018 (age up to 36 months). EEG was performed to detect CEDs up to 24 months old. Data on obstetric, demographic, and clinical signs; cranial computed tomography (CT); ophthalmology examination; anti-seizure medication; growth; and motor development were collected. Fisher's exact test was used to verify the associations between categorical variables, and the T- test was used to compare the mean z-scores of anthropometric measurements between the groups with and without CED. ResultsCEDs were identified in 41 (54.67 %) children. The mean age of CEDs identification was 12.24 ± 6.86 months. Bilateral CEDs were shown in 62.89 % of EEGs. CEDs were associated with severe congenital microcephaly, defined by z-score >3 standard deviation of head circumference (HC) below the mean for sex and age (p = 0.025), and worse outcomes, including first seizure before 6 months (p = 0.004), drug-resistant epilepsy (p < 0.001), chorioretinal scarring or mottling (p = 0.002), and severe CT findings (p = 0.002). The CED group had lower mean z-scores of HC up to 24 months of age. ConclusionThis is the first description of the prevalence and significance of CEDs that also remains during wakefulness in patients with CZS. New investigations may suggest that it is more appropriate to classify the EEG not as a CED, but as a periodic pattern. Anyway, CEDs may be a marker of neurological severity in children with CSZ.

Sturge-Weber syndrome: an update for the pediatrician.

Sturge-Weber syndrome (SWS) is a rare congenital neurocutaneous disorder characterized by the simultaneous presence of both cutaneous and extracutaneous capillary malformations. SWS usually presents as a facial port-wine birthmark, with a varying presence of leptomeningeal capillary malformations and ocular vascular abnormalities. The latter may lead to significant neurological and ocular morbidity such as epilepsy and glaucoma. SWS is most often caused by a somatic mutation involving the G protein subunit alpha Q or G protein subunit alpha 11 gene causing various alterations in downstream signaling pathways. We specifically conducted a comprehensive review focusing on the current knowledge of clinical practices, the latest pathophysiological insights, and the potential novel therapeutic avenues they provide. A narrative, non-systematic review of the literature was conducted, combining expert opinion with a balanced review of the available literature. A search of PubMed, Google Scholar and Embase was conducted, using keywords "Sturge-Weber Syndrome" OR "SWS", "Capillary malformations", "G protein subunit alpha 11" OR "G protein subunit alpha Q". One of the hallmark features of SWS is the presence of a port-wine birthmarkat birth, andforehead involvement is most indicative for SWS. The most common ocular manifestations of SWS areglaucoma andchoroidal hemangioma.Glaucomapresentsin either in infancy (0-3years of age) or later in life.Neurological complications are common in SWS, occurring in about 70%-80% of patients, with seizures being the most common one.SWS significantly impacts the quality of life for patients and their families, and requires a multidisciplinary approach for diagnosis and treatment. Currently, no disease-modifying therapies exist, andtreatment is mostly focused on symptoms or complications as they arise. CONCLUSIONS: SWS remains a complex and heterogeneous disorder. Further research is needed to optimize diagnostic and therapeutic strategies, and to translate insights from molecular pathogenesis to clinical practice.

GFRA4 improves the neurogenic potential of enteric neural crest stem cells via hedgehog pathway.

Hirschsprung disease (HSCR) is a congenital intestinal disease characterised by functional obstruction of the colon. Herein, we investigated the role and mechanism of the gene GFRA4 in HSCR. GFRA4 expression in the ganglionic and aganglionic segment tissues in patients with HSCR and healthy colon tissues were detected using qRT-PCR, western blot, and immunohistochemistry. Cell proliferation, cycle distribution, apoptosis, changes in mitochondrial membrane potential, and differentiation were assessed in mouse enteric neural crest stem cells (ENCSCs) using the CCK-8 assay, EdU staining, flow cytometry, JC-1 probe, and immunofluorescence, respectively. GSEA analysis was performed to screen the signaling pathways regulated by GFRA4. GFRA4 was downregulated in aganglionic segment tissues compared to control and ganglionic segment tissues. GFRA4 overexpression promoted proliferation and differentiation, and inhibited apoptosis in ENCSCs, while GFRA4 down-regulation had the opposite result. GFRA4 activated the hedgehog pathway. GFRA4 overexpression enhanced the expression of key factors of the hedgehog pathway, including SMO, SHH, and GLI1. However, GFRA4 down-regulation reduced their expression. An antagonist of hedgehog pathway, cyclopamine, attenuated the effect of GFRA4 overexpression on proliferation, differentiation, and apoptosis of ENCSCs. GFRA4 promotes proliferation and differentiation but inhibits apoptosis of ENCSCs via the hedgehog pathway in HSCR. This study confirms that GFRA4 improves the proliferation and differentiation of ENCSCs via modulation of the hedgehog pathway. This study for the first time revealed the role and the mechanism of the action of GFRA4 in HSCR, which indicates that GFRA4 may play a role in the pathological development of HSCR. Our findings may lay the foundation for further investigation of the mechanisms underlying HSCR development and into targets of HSCR treatment.

Newly recognized orbital malformations in kabuki syndrome: A case report.

Kabuki syndrome (KS) is a rare congenital disorder with distinctive characteristics. Herein, we describe a KS patient carrying a novel mutation in the KMT2D gene, c.11785C > T (p.Gln3929*). The patient presented with typical eyelid deformities, including eversion of the lateral lower eyelids, long palpebral fissures, hypertelorism, and medial epicanthus. Orbital computed tomography revealed orbital bone malformation with temporally and inferiorly displaced zygomatic bone. The bilateral orbits were shallow with an enlarged angle between the lateral walls. Zygomatic and maxillary bone dysplasia were also observed. Orbital bone anomalies are thought to be one of the characteristics of KS.

SNP and Structural Study of the Notch Superfamily Provides Insights and Novel Pharmacological Targets against the CADASIL Syndrome and Neurodegenerative Diseases.

The evolutionary conserved Notch signaling pathway functions as a mediator of direct cell-cell communication between neighboring cells during development. Notch plays a crucial role in various fundamental biological processes in a wide range of tissues. Accordingly, the aberrant signaling of this pathway underlies multiple genetic pathologies such as developmental syndromes, congenital disorders, neurodegenerative diseases, and cancer. Over the last two decades, significant data have shown that the Notch signaling pathway displays a significant function in the mature brains of vertebrates and invertebrates beyond neuronal development and specification during embryonic development. Neuronal connection, synaptic plasticity, learning, and memory appear to be regulated by this pathway. Specific mutations in human Notch family proteins have been linked to several neurodegenerative diseases including Alzheimer's disease, CADASIL, and ischemic injury. Neurodegenerative diseases are incurable disorders of the central nervous system that cause the progressive degeneration and/or death of brain nerve cells, affecting both mental function and movement (ataxia). There is currently a lot of study being conducted to better understand the molecular mechanisms by which Notch plays an essential role in the mature brain. In this study, an in silico analysis of polymorphisms and mutations in human Notch family members that lead to neurodegenerative diseases was performed in order to investigate the correlations among Notch family proteins and neurodegenerative diseases. Particular emphasis was placed on the study of mutations in the Notch3 protein and the structure analysis of the mutant Notch3 protein that leads to the manifestation of the CADASIL syndrome in order to spot possible conserved mutations and interpret the effect of these mutations in the Notch3 protein structure. Conserved mutations of cysteine residues may be candidate pharmacological targets for the potential therapy of CADASIL syndrome.

Rhabdomyomatous Mesenchymal Hamartoma: Report of 4 Cases With Histochemical and Immunohistochemical Findings and Emphasis on Potential Pitfalls.

Rhabdomyomatous mesenchymal hamartoma (RMH) typically presents as a congenital midline head and neck cutaneous polyp in infants. Perianal and mucocutaneous lesions have been reported, and recently, acquired adult-onset variants have been proposed. This makes the true prevalence, etiopathogenesis, and clinicopathologic distribution and classification of RMHs in children compared with those in adults uncertain. We performed a retrospective review to highlight the salient histopathologic, histochemical, and immunohistochemical features in RMHs and to emphasize their specific clinicopathologic criteria to avoid diagnostic pitfalls. We found 4 (0.3%) infants [2 female infants and 2 male infants, average age: 4 months] with mental, nasal, lingual, and perianal midline RMHs (average size: 1.0 cm) of 1303 patients with cutaneous polypoid lesions. Three were isolated, and 1 was associated with Goldenhar syndrome. The cutaneous polyps demonstrated intermixed skeletal muscle, adipose, and fibrocollagenous core stroma that extended into the dermis and around the dermal appendages. The lingual lesion demonstrated skeletal muscle and fibrocollagenous stroma with prominent nerve bundles and little adipose tissue. All showed interstitial loose mesenchyme. Masson trichome demarcated the triphasic stromal components. Alcian blue demonstrated the loose myxoid mesenchyme. Elastic van Gieson did not show elastic fibers. Desmin demonstrated the skeletal muscle bundles, S100 highlighted the adipose tissue lobules and the nerve bundles, and CD34 displayed the mesenchymal stroma. Ki67 showed a low proliferation index in the loose mesenchyme. Smooth muscle actin did not reveal smooth muscle bundles, but with CD31, they highlighted the thick blood vessels. CD117 revealed prominent mast cells. From our retrospective review series, 4 cases that originally diagnosed as RMHs were excluded. Likewise, we found some examples of the reported cases in the English literature that might have been mistaken for RMHs. This is because they did not fulfill the diagnostic clinicopathologic criteria. RMH constitutes a rare entity with specific clinicopathologic features. Most lesions are isolated. Some are associated with congenital anomalies and syndromes. Strict clinicopathologic diagnostic criteria should be applied to avoid mislabeling look-alike lesions for RMHs.

Inappropriate Defibrillator Shock Due to Oversensing. What to Do?

In spite of advanced designs of implantable cardioverter defibrillators (ICD) lead fracture remains the most frequent complications. ICD interrogation is mandatory for the diagnosis of all type of lead failures. We report the case of an 18 years old boy, diagnosed with Jarvell and Lange Nielsen syndrome since he was 2 years. He received first Nadolol then he got ICD and a prophylactic left sympathectomy after he had a cardiac arrest. One year later, the ICD started delivering shocks, appropriate at first then inappropriate due to oversensing. Long QT syndrome is a rare congenital disorder characterized by repetitive episode of syncope and cardiac arrest due to polymorphic ventricular tachycardia. The treatment is mostly pharmaceutical with B-blockers. The indication for an ICD is in class I for patients who survived cardiac arrest, and for patients who experience recurrent syncopal events under B-blockers. On the other hand, in case of contraindicated or not tolerated medical therapy, ICD is recommended as a class IIa, according the ESC guidelines of 2022. An ICD must be interrogated frequently and have its measurements reviewed in order to detect lead dysfunction. The detection of high impedance suggests conductor fracture along with inappropriate defibrillator shocks delivered by the ICD. Oversensing with normal pacing impedance is the initial electrical abnormality with either conductor fracture.(4) The fractured lead will either be left inside the patient or removed, depending on specific factors related to the patient and the ICD. (5)

81 Liver Transplant as Definitive Therapy for Immune Defects Associated with Congenital Disorder of Glycosylation Type 1 B

81 Liver Transplant as Definitive Therapy for Immune Defects Associated with Congenital Disorder of Glycosylation Type 1 B

A RETROSPECTIVE REVIEW OF THE THERAPEUTIC MANAGEMENT OF SOFT TISSUE AND JOINT RANGE OF MOTION DURING LOWER LIMB LENGTHENING IN CHILDREN

IntroductionSheffield Children's Hospital specialises in limb lengthening for children. Soft tissue contracture and loss of range of motion at the knee and ankle are common complications. This review aims to look at therapeutic techniques used by the therapy team to manage these issues.Materials &amp; MethodsA retrospective case review of therapy notes was performed of femoral and tibial lengthening's over the last 3 years. Included were children having long bone lengthening with an iIntramedullary nail, circular frame or mono-lateral rail. Patients excluded were any external fixators crossing the knee/ankle joints.Results20 tibial and 25 femoral lengthening's met the inclusion criteria. Pathologies included, complex fractures, limb deficiency, post septic necrosis and other congenital conditions leading to growth disturbance. All patients had issues with loss of motion at some point during the lengthening process. The knee and foot/ankle were equally affected. Numerous risk factors were identified across the cohort. Treatment provided included splinting, serial casting, bolt on shoes, exercise therapy, electrical muscle stimulation and passive stretching.ConclusionsLoss of motion in lower limb joints was common. Patients at higher risk were those with abnormal anatomy, larger target lengthening's, poor compliance or lack of access to local services. Therapy played a significant role in managing joint motion during treatment. However, limitations were noted. No one treatment option gave preferential outcomes, selection of treatment needed to be patient specific. Future research should look at guidelines to aid timely input and avoid secondary complications.

Systematic review of continuous positive airway pressure for the treatment of obstructive sleep apnea in patients with Down syndrome

RATIONALE Down syndrome (DS) is a congenital condition highly associated with obstructive sleep apnea (OSA), a complex disorder with significant clinical consequences. Treatment options for OSA encompass drugs, intraoral devices, surgery, and continuous positive airway pressure (CPAP) Therapy. OBJECTIVES This systematic review aims to evaluate the impact of CPAP to treat OSA in individuals with DS, generating valuable insights on how to manage the condition in this population, preventing complications, and improving quality of life. METHODS A literature search was conducted using the MEDLINE (PubMed), EMBASE, Cochrane Library and LILACS databases. The search strategy combined individuals with DS and intervention with CPAP. MEASUREMENTS Observational studies, randomized and non-randomized clinical trials that reported outcomes such as AHI, mean oxygen saturation, EQ-5D, OSA-18, adherence, tolerance, ESS or ESS-CHAD were included. The methodological quality and risk of bias of the included studies were evaluated using ROB 2.0, ROBINS-I, and a questionnaire for non-comparative studies. The certainty of evidence was rated according to GRADE. MAIN RESULTS Eight studies were included, most favored CPAP in DS patients. Overall, CPAP reduced obstructive events during sleep, and patients showed good adherence and tolerance. Individuals also experienced improvements in daytime sleepiness; however, the intervention did not alter the patients’ quality of life. All outcomes were assessed with low or very low certainty of evidence. CONCLUSION The evidence found should be cautiously evaluated for extrapolation to clinical practice, due to methodological limitations and low-certainty outcomes.

ReDIP, the Italian network for the diagnosis of congenital platelet function disorders

Congenital platelet function disorders (cPFD) are associated with an increased risk of mucocutaneous bleeding of various levels of severity; they may be classified based on abnormalities of platelet components that share common characteristics: i) platelet receptors for adhesive proteins; ii) platelet receptors for soluble agonists; iii) platelet granules; iv) signal transduction pathways; v) procoagulant phospholipids; less well characterized PFD aregrouped in a sixth category of miscellaneous abnormalities [...].