Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS): challenges in diagnosis and management.

Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a rare, congenital functional intestinal obstruction, characterised by megacystis (bladder distention in the absence of mechanical obstruction), microcolon and intestinal hypoperistalsis (dysmotility).We are reporting a case of a female child with normal antenatal course who presented with recurrent episodes of abdominal distension since the second day of life and underwent negative exploratory laparotomy on multiple occasions. She also had urinary retention with a grossly distended bladder, requiring drainage by clean intermittent catheterisation. Surgical procedures for bowel decompression, including gastrostomy and ileostomy, were carried out without success. Genetic analysis revealed a mutation in the human smooth muscle (enteric) gamma-actin gene (ACTG2 gene), clinching the diagnosis of MMIHS. The patient was managed with parenteral nutrition and prokinetic medications and tolerated jejunostomy feeds for a brief period before she succumbed to the illness.Female neonates or infants presenting with abdominal distension and dilated urinary tract should be investigated for MMIHS early on. A timely diagnosis will enable the early involvement of a multidisciplinary team to provide the best options available for management.

Keratosis pilaris treatment paradigms: assessing effectiveness across modalities.

This review aims to present a comprehensive synthesis of the existing treatment modalities for keratosis pilaris (KP) and evaluate their therapeutic efficacy. KP is a prevalent chronic dermatological condition typified by its unique 'chicken skin appearance', with the cheeks being the most commonly involved sites. Numerous therapeutic interventions have emerged, given its substantial prevalence and impact on skin aesthetics and psychological wellbeing. Nonetheless, a consistent therapeutic response has been challenging to achieve. This review endeavours to collate and critically appraise the current treatment landscape for KP. An exhaustive literature search was performed using databases such as Ovid, PubMed and Scopus. From an initial count of 459 articles identified after deduplication, 52 were selected for inclusion after a thorough full-text examination for articles with concrete outcome data highlighting the efficacies of different therapeutic modalities; articles that lacked data or were tangential to the core focus on KP treatment were excluded. The included articles were then catalogued based on the nature of treatment strategies and their respective outcomes. Among the various therapeutic interventions, laser and light modalities appear to be supported by the most substantial evidence base. Notably, the Nd:YAG (neodymium-doped yttrium-aluminium-garnet) laser, attributed to its longer wavelength, emerged as a preferred option. While other therapeutic avenues have also exhibited notable improvements in skin texture and discolouration relative to baseline, the inconsistency in outcome measures underscores the need for a standardized, KP-specific scoring system to foster a more coherent comparison across treatments. Based on the current evidence, Nd:YAG laser therapy demonstrates promising effectiveness with a relatively favourable side-effect profile. However, the landscape of KP treatment is multifaceted, and further studies are essential to solidify recommendations.

[Oculo-facio-cardio-dental syndrome caused by BCOR gene mutations: a case report]. / BCORåŸºå› çªå˜è‡´æ–°ç”Ÿå„¿çœ¼-面-心-牙综合征1例.

A full-term female infant was admitted at 5 hours after birth due to heart malformations found during the fetal period and cyanosis once after birth. Mmultiple malformations of eyes, face, limbs, and heart were noted. The whole-exome sequencing revealed a pathogenic heterozygous mutation, c.2428C>T(p.Arg810*), in the BCOR gene. The infant was then diagnosed with oculo-facio-cardio-dental syndrome. He received assisted ventilation to improve oxygenation and nutritional support during hospitalization. Right ventricular double outlet correction was performed 1 month after birth. Ocular lesions were followed up and scheduled for elective surgery. The possibility of oculo-facio-cardio-dental syndrome should be considered for neonates with multiple malformations of eyes, face, and heart, and genetic testing should be performed as early as possible to confirm the diagnosis; meanwhile, active ophthalmic and cardiovascular symptomatic treatment should be given to improve the prognosis.

Joubert syndrome: Molecular basis and treatment.

Joubert syndrome (JS; MIM PS213300) is a rare genetic autosomal recessive disease characterized by cerebellar vermis hypoplasia, a distinctive malformation of the cerebellum and the so-called "molar tooth sign." Other characteristic features are hypotonia with lateral ataxia, intellectual disability/mental retardation, oculomotor apraxia, retinal dystrophy, abnormalities in the respiratory system, renal cysts, hepatic fibrosis, and skeletal changes. Such pleiotropic characteristics are typical of many disorders involving primary cilium aberrations, providing a significant overlap between JS and other ciliopathies such as nephronophthisis, Meckel syndrome, and Bardet-Biedl syndrome. This review will describe some characteristics of JS associated with changes in 35 genes, and will also address subtypes of JS, clinical diagnosis, and the future of therapeutic developments.

A Patient with Kabuki Syndrome Mutation Presenting with Very Severe Aplastic Anemia.

Kabuki syndrome (KS) is a rare congenital disorder commonly complicated by humoral immunodeficiency. Patients with KS present with mutation in the histone-lysine N-methyltransferase 2D (KMT2D) gene. Although various KMT2D mutations are often identified in lymphoma and leukemia, those encountered in aplastic anemia (AA) are limited. Herein, we present the case of a 45-year-old Japanese man who developed severe pancytopenia and hypogammaglobulinemia. He did not present with any evident malformations, intellectual disability, or detectable levels of autoantibodies. However, B-cell development was impaired. Therefore, a diagnosis of very severe AA due to a hypoplastic marrow, which did not respond to granulocyte colony-stimulating factor, was made. The patient received umbilical cord blood transplantation but died from a Pseudomonas infection before neutrophil engraftment. Trio whole-exome sequencing revealed a novel missense heterozygous mutation c.15959G >A (p.R5320H) in exon 50 of the KMT2D gene. Moreover, Sanger sequencing of peripheral blood and bone marrow mononuclear cells and a skin biopsy specimen obtained from this patient identified this heterozygous mutation, suggesting that de novo mutation associated with KS occurred in the early embryonic development. Our case showed a novel association between KS mutation and adult-onset AA.

Treatment of keratosis pilaris and its variants: a systematic review.

INTRODUCTION: Keratosis pilaris (KP) is a common, benign skin condition of follicular hyperkeratosis. Although KP is asymptomatic, the cosmetic appearance of KP can lead to psychosocial distress among patients. New emerging treatments are increasingly being utilized. Yet, there is little to no summative data on the treatments of KP and its subtypes. OBJECTIVE: To summarize existing literature on treatments for KP and its subtypes. METHODS: A comprehensive search was performed using Pubmed/MEDLINE, Embase and Web of Science databases. The search identified 1150 non-duplicated articles, and 47 articles were included in the review. The primary outcomes measured were KP treatment type and the degree of improvement following therapy. FINDINGS: Our findings demonstrate that the most supported form of treatment for KP is laser therapy, particularly the QS:Nd YAG laser. Topical treatments - including Mineral Oil-Hydrophil Petrolat, tacrolimus, azelaic acid, and salicylic acid - are also effective at least for improving the appearance of KP. CONCLUSION: While the measured treatment outcomes varied among studies, laser therapy appears to be the most effective form of treatment. Use of topicals also improved KP lesions.

Clubfeet and congenital constriction band syndrome.

BACKGROUND: Clubfeet and constriction band syndrome is a very rare non-idiopathic condition. Treatment is often difficult and the recurrence deformity rate is high. The purpose of this study was to assess the effectiveness of Ponseti method in the treatment of congenital constriction band syndrome accompanied by clubfoot deformity and lymphedema. CASE PRESENTATION: We are presenting an interesting case of bilateral clubfeet and congenital circumferential constriction band syndrome in the lower limb. Ponseti method of correcting the congenital clubfoot deformity was applied. Constriction band release is accomplished by two stages completely excising the fibrous band and multiple two-stage Z-plasties on the right calf. CONCLUSION: The results of this study indicate that the Ponseti method of gentle, systematic manipulation and weekly cast changes is an effective treatment of non-idiopathic clubfoot distal to congenital amniotic constriction band.

22q11.2 deletion syndrome: 20 years of experience from two pediatric immunology units and review of clues for diagnosis and disease management.

INTRODUCTION AND OBJECTIVES: The purpose of this study was to evaluate patients diagnosed with 22q11.2 deletion syndrome and determine the clues directing to diagnosis and evaluation of immunological findings for excellent management of the disease. MATERIAL AND METHODS: Thirty-three pediatric patients with 22q11.2 deletion syndrome diagnosed between 1998 and 2019 at Pediatric Immunology Division of Ege University Faculty of Medicine and SBU Izmir Dr Behcet Uz Children's Education and Research Hospital were evaluated. RESULTS: This study includes the largest case series reported from Turkey. Congenital cardiac anomalies were the most common pathology associated with the syndrome (90.9%). Hypocalcemic symptoms were observed in 13 patients (40%). Twenty-two of the 33 (66.6%) patients were diagnosed before two years of age. Autoimmune diseases, dysmorphic facial findings, recurrent infections, growth retardation, and speech impairment were other clues for diagnosis in older patients. Clinical spectrum and immunological abnormalities of this syndrome are quite variable. All T-cell subset counts were less than 5th percentile below median by age in one patient (3%) and 10 patients had normal all T-cell subset counts (30.3%). Overall, 69.6% of the patients had normal IgG, IgA, and IgM levels and two patients had panhypogammaglobulinemia. Recurrent infections were revealed in 75.7% of the patients during follow-up. CONCLUSIONS: Presence of cardiac anomaly is more helpful in the diagnosis, especially under two years of age. Patients with immunologically high or standard risk did not show any difference in terms of numbers and severity of infections and autoimmunity.

c.1898C>G/p.Ser633Trp Mutation in Alpha-L-Iduronidase: Clinical and Structural Implications.

Mucopolysaccharidosis type I is a rare autosomal recessive genetic disease caused by deficient activity of α-L-iduronidase. As a consequence of low or absent activity of this enzyme, glycosaminoglycans accumulate in the lysosomal compartments of multiple cell types throughout the body. Mucopolysaccharidosis type I has been classified into 3 clinical subtypes, ranging from a severe Hurler form to the more attenuated Hurler-Scheie and Scheie phenotypes. Over 200 gene variants causing the various forms of mucopolysaccharidosis type I have been reported. DNA isolated from dried blood spot was used to sequencing of all exons of the IDUA gene from a patient with a clinical phenotype of severe mucopolysaccharidosis type I syndrome. Enzyme activity of α-L-iduronidase was quantified by fluorimetric assay. Additionally, a molecular dynamics simulation approach was used to determine the effect of the Ser633Trp mutation on the structure and dynamics of the α-L-iduronidase. The DNA sequencing analysis and enzymatic activity shows a c.1898C>G mutation associated a patient with a homozygous state and α-L-iduronidase activity of 0.24 µmol/L/h, respectively. The molecular dynamics simulation analysis shows that the p.Ser633Trp mutation on the α-L-iduronidase affect significant the temporal and spatial properties of the different structural loops, the N-glycan attached to Asn372 and amino acid residues around the catalytic site of this enzyme. Low enzymatic activity observed for p.Ser633Trp variant of the α-L-iduronidase seems to lead to severe mucopolysaccharidosis type I phenotype, possibly associated with a perturbation of the structural dynamics in regions of the enzyme close to the active site.

Creating a collaborative program for the care of children with colorectal and pelvic problems.

The treatment of patients with colorectal disorders and their associated urologic, gynecologic, gastrointestinal, spinal, and orthopedic anomalies requires care from various medical and surgical specialties over the course of their lifetime. This is ideally handled by a collaborative center which facilitates the assessment and development of a long-term patient care plan among multiple specialties which can enhance the quality of care, improve communication among different specialties, and improve patient satisfaction and outcomes. We describe the process, as well as lessons learned in developing such a center.

Importance of education and the role of the patient and family in the care of anorectal malformations.

During this early part of the 21st century online technology has prompted many major advances in medical care. In this section we argue that this is particularly evident in the treatment and care of patients born with Anorectal Malformation (ARM) and Hirschsprung's Disease (HD). Our stories show that anyone born with these complex colorectal conditions in the 20th century was destined to a life of isolation and stigma. Here we explore the lack of understanding and recognition of the psychological effects on children and families which has characterised this period. We show that advances in clinical practice has been supported by developing social media platforms. There has been a rapid creation of online support groups for patients and families which has enabled survivors' greater access to patient and parent organizations across the globe and thereby stimulated a sense of belonging and solidarity. Online technology and social media platforms have also opened up the opportunity for pediatric medical professionals to provide a greater level of patient education. There is no doubt families have become much more aware of the complexities of ARM & HD and achieved greater comfort and understanding of their needs. We have generated "lightbulb moments" for pediatric providers with adult ARM & HD patients, enabling them to share their lived experiences in a therapeutic exchange. In the past survivors felt they were abandoned by the adult healthcare system. We are seeing evidence-based research of major psychosocial issues experienced by adult patients and, as a result, improved understanding of how to treat ARM & HD survivors across their whole of life journey. The winds of change continue to direct our cohorts to a mature approach based on improving levels of interactive communication and education. We argue that this maturity has mostly been facilitated by the use of online technology and the ensuing collaboration between providers and patient and parent organizations.

Long-term urologic and gynecologic follow-up and the importance of collaboration for patients with anorectal malformations.

Anorectal malformations (ARM) are well recognized to be associated with anomalies in other organ systems. The introduction of screening protocols has increased the diagnosis of these anomalies and greater collaboration with other specialties has influenced the treatment and follow-up of patients with ARMs. Much of the medical literature regarding the treatment of anorectal malformations has focused on technical details of operations and early post-surgical outcomes. Recently, an increase in published data regarding the long-term sequelae of an ARM diagnosis has resulted in an emphasis extended follow up in this population. Patient support groups have highlighted complex issues in ARM patients persist into adulthood have advocated for improved transitional care. This article describes the benefits of long-term follow-up and identifies key issues in ARM patients with respect to urologic and gynecologic health. A collaborative model of care is outlined and suggested timings of screening for potential problems is described.

Anomalías congénitas y comorbilidad en neonatos con Síndrome de Down / Congenital anomalies and comorbidities in neonates with Down Syndrome

INTRODUCCIÓN: El Síndrome de Down se presenta en 2,5 de 1.000 recién nacidos vivos chilenos. Presentan más anomalías congénitas y comorbilidades que la población general, aumentando su tasa de hospitalización. OBJETIVO: Describir las anomalías congénitas y comorbilidades de neonatos con Síndrome de Down nacidos y/u hospitalizados en la década 2008-2018. PACIENTES Y MÉTODO: Retrospectiva mente se revisaron registros de los pacientes nacidos y/u hospitalizados dentro de sus 28 días de vida entre el 1 de enero de 2008 y el 31 de diciembre de 2018. Para cada paciente se consignó: edad materna, antecedentes familiares de Síndrome de Down, antecedentes pre y perinatales y resultado de estudio genético. Se consignó la edad al ingreso, el motivo principal de ingreso, comorbilidades, días de hospitalización y fallecimiento. Se excluyeron dos pacientes con más del 50% de ficha in completa. Se exploraron asociaciones entre morbilidades, anomalías y fallecimiento. RESULTADOS: 140 de 79.506 (0,2%) recién nacidos vivos fueron diagnosticados con Síndrome de Down en el período neonatal. 24,7% fueron prematuros y 26,4% tuvieron bajo peso para su edad gestacional. Los porcentajes de morbilidad y hospitalización fueron 83,6% y 90%. La principal causa de ingreso fue la poliglobulia, y la más frecuente hiperbilirrubinemia. Fallecieron 4 pacientes (2,9%) y 70,7% presentó alguna una anomalía congénita, principalmente cardíaca. La mediana de edad materna fue de 36 años y 57,1% tenía 35 años o más. CONCLUSIONES: Esta investigación aporta información relevante para optimizar el manejo perinatal y el seguimiento de los pacientes con Síndrome de Down.

INTRODUCTION: In Chile, Down syndrome has a prevalence of 2.5 in 1,000 live births. These patients present more congenital anomalies and comorbidities than the general population, increasing their hospitaliza tion rate. OBJECTIVE: To describe congenital anomalies and comorbidities of neonates with Down syndrome born and/or hospitalized between 2008 and 2018. PATIENTS AND METHOD: We conducted a retrospective review of patient's medical records born and/or hospitalized during their first 28 days of life between January 1st, 2008, and December 31st, 2018. For each patient, we recorded maternal age, familiar cases of Down Syndrome, pre and perinatal history, genetic study result, as well as age at admission, reason for hospitalization, comorbidities, length of stay, and death. Two patients that had more than 50% of incomplete medical records were excluded. We studied the associations between comorbidities, congenital anomalies, and death. RESULTS: 140 in 79,506 newborns (0.2%) were diagnosed at our center with Down Syndrome in their neonatal period. 24.7% were born preterm and 26.4% had low birth weight for gestational age. Morbidities and hospitalizations were present in 83.6% and 90%, of the study population, respectively. The main reason for hospitalization was polycythemia and the most frequent was hyperbilirubinemia. Four patients died (2.9%) and 70.7% presented at least one congenital anomaly, mainly heart disease. Median maternal age was 36 years and 57.1% of mothers were aged 35 or older. CONCLUSIONS: This cohort of patients with Down Syndrome provides important information for the optimization of their perinatal management and follow-up.

Neonatal hyperinsulinemic hypoglycemia: case report of kabuki syndrome due to a novel KMT2D splicing-site mutation.

BACKGROUND: Persistent neonatal hypoglycemia, owing to the possibility of severe neurodevelopmental consequences, is a leading cause of neonatal care admission. Hyperinsulinemic hypoglycemia is often resistant to dextrose infusion and needs rapid diagnosis and treatment. Several congenital conditions, from single gene defects to genetic syndromes should be considered in the diagnostic approach. Kabuki syndrome type 1 (MIM# 147920) and Kabuki syndrome type 2 (MIM# 300867), can be associated with neonatal hyperinsulinemic hypoglycemia. PATIENT PRESENTATION: We report a female Italian (Sicilian) child, born preterm at 35 weeks gestation, with persistent hypoglycemia. Peculiar facial dysmorphisms, neonatal hypotonia, and cerebellar vermis hypoplasia raised suspicion of Kabuki syndrome. Hyperinsulinemic hypoglycemia was confirmed with glucagon test and whole-exome sequencing (WES) found a novel heterozygous splicing-site mutation (c.674-1G > A) in KMT2D gene. Hyperinsulinemic hypoglycemia was successfully treated with diazoxide. At 3 months corrected age for prematurity, a mild global neurodevelopmental delay, postnatal weight and occipitofrontal circumference growth failure were reported. CONCLUSIONS: Kabuki syndrome should be considered when facing neonatal persistent hypoglycemia. Diazoxide may help to improve hyperinsulinemic hypoglycemia. A multidisciplinary and individualized follow-up should be carried out for early diagnosis and treatment of severe pathological associated conditions.

Anesthesia for Stüve-Wiedemann syndrome: a rare adult patient case report.

Stüve-Wiedemann syndrome (SWS) is a rare genetic disorder characterized by skeletal dysplasia and severe dysautonomia, evidencing a difficult airway approach and likely increased malignant hyperthermia susceptibility. Developmental dysmorphism classically worsens with age, therefore translating in a poor prognosis. In this article, we describe a case of a 27-year-old woman diagnosed with SWS proposed for abscess drainage under dissociative anesthesia. This patient has outlived the life expectancy described for SWS, acknowledging the importance of reporting this rare adult clinical case in what SWS anesthetic management is concerned.

Currarino Syndrome: A Rare Condition With Potential Connection to Neuroendocrine Tumors.

OBJECTIVES: Currarino syndrome (CS) is a congenital disorder that consists of a triad of anomalies: presacral mass, sacral dysgenesis, and anorectal malformations. Few cases of CS with neuroendocrine tumors (NETs) have been reported. In this study, we sought to determine the prevalence and characteristics of NET in patients with CS. METHODS: Mayo Clinic electronic medical records were searched for patients with CS. Data on demographics, CS diagnosis, family history, genetic testing, and NET diagnosis were extracted. RESULTS: A total of 26 patients with CS were identified with 3 (11.5%) of them having an additional diagnosis of NET. Three patients had a family history of NET (11.53%), and 7 patients had a family history of CS (26.9%). Of the 3 NET/CS patients, 2 had a confirmed primary NET from the presacral mass, with the third patient demonstrating focal uptake on the somatostatin receptor imaging within the presacral. Two patients received octreotide, followed by peptide receptor radionuclide therapy. The other patient was not treated because of complete resection of presacral mass and is currently undergoing surveillance scans. CONCLUSIONS: In our patients with CS, the prevalence of NET is 11.53%. The coexistence of 2 rare conditions, CS and presacral NET, suggests that there may be an etiological connection.

Light and Laser Treatments for Keratosis Pilaris: A Systematic Review.

BACKGROUND: Keratosis pilaris (KP) is a common hereditary keratinization disorder. Keratosis pilaris rubra and KP atrophicans faciei are less frequent variants of the disease. Topical treatments often yield ineffective and temporary results. OBJECTIVE: The objective of this article is to review and assess all the studies that used light and laser devices to treat KP and its variants. MATERIAL AND METHODS: On January 15, 2017, an online search of the MEDLINE, Embase, and Cochrane databases was performed using the following combination of keywords: "keratosis pilaris" and "treatment." RESULTS: Seventeen studies related to light and laser treatments were retained for analysis. The total number of treated patients was 175. Of which, 22 patients had KP atrophicans faciei, 17 patients had KP rubra, and 136 patients had KP. CONCLUSION: Light and laser devices have been emerging as promising therapeutic options for a disfiguring disease that still lacks, until today, an effective long-term treatment.

Ayurveda management of keratosis pilaris - a case report.

OBJECTIVES: Keratosis pilaris (KP) is the condition of the skin with extensive keratin follicular plugging. It may be associated with the erythema. The upper arm extensor area, shoulders, back of neck and thighs, as well as face and the upper trunk are the areas of presentation. Available medications for KP give only symptomatic relief, while some produce serious side effects. There is no proven universal treatment for the disease that can provide complete recovery. Ayurveda management of KP is not yet reported. CASE PRESENTATION: A 26-year-old male patient, presented with main complaints started with papular lesions over his right shoulder, chest and upper back along and later with pustular lesions in the past 2 weeks. The condition was associated with redness, mild swelling and itching. The case was diagnosed as Keratosis pilaris based on its presentation, site, and pathogenesis. Also by analyzing the extent of vitiation of dosas (morbidities), the Vata kapha pitta hara line of treatment was adopted, which was accomplished in two phases i. e. Sodhana Cikitsa and Samana Cikitsa. CONCLUSION: Both internal and external treatments along with diet restrictions were found effective in arresting the pathogenesis and recovery in a short period. All the symptoms associated with the condition were completely cured with no signs of re-occurrence.