Klippel Trenaunay Syndrome with Angiokeratoma Circumscriptum Naeviforme and Bilateral Congenital Anorchia: A Rare Association

Klippel-Trenaunay syndrome (KTS) is not a common congenital vascular abnormality. A trio of capillary malformation, venous varicosities, and bony or soft-tissue hypertrophy define this syndrome. Significant morbidities associated with this illness include bleeding, deep vein thrombosis, and embolic consequences. Angiokeratoma circumscriptum naeviforme (ACN) is indeed a congenital variant of angiokeratoma that appears as a hyperkeratotic plaque on the lower extremity. Bilateral congenital anorchia (BCA) is the total lack of testicular tissue in a male with a normal phenotype and karyotype. KTS has been linked to ACN. Here we presented an 8-year-old male child who came with a swollen left thigh and the right side of his face with overlying blackish nodules on his left thigh and scrotum. The patient was diagnosed as KTS with angiokeratoma circumscriptum naeviforme and bilateral congenital anorchia based on his history, imaging studies and the typical clinical features of the disease.

Trabeculectomy with Ologen implant versus mitomycin C in congenital glaucoma secondary to Sturge Weber Syndrome

AIM： To compare the efficacy and safety of collagen matrix implant [Ologen（OLO） implant] versus mitomycin C（MMC） with subscleral trabeculectomy（SST） for the surgical treatment of congenital glaucoma（CG） in SturgeWeber Syndrome（SWS）.METHODS： A prospective comparative randomized study of 20 eyes of 16 patients with CG associated with SWS was divided into two groups. The first group（MMC Group） included 10 eyes that were subjected to SST with MMC. The second group（OLO Group） included 10 eyes that were subjected to trabeculectomy with a collagen matrix implant（OLO implant）. Postoperative evaluation included intraocular pressure（IOP） level, bleb evaluation, complications, and the need for further medication or surgical intervention. RESULTS： The mean preoperative IOP was 29±3.16 mm Hg in MMC and 29.8±3.08 mm Hg in OLO eyes. Mean 12-month percentage reduction in IOP was significant in both groups（57.9% and 56.3%）. At the end of the 12 postoperative follow-up month, in the MMC Group, 80% of eyes achieved the complete success, 20% of eyes had qualified success with no failed surgery in comparison to OLO Group which 70% of eyes achieved the complete success, 20% of eyes had qualified success with 10% failed surgery. In terms of complications, the MMC Group had a higher rate of complications than the OLO Group in the form of thin polycystic bleb in 6 eyes（60%）, blebitis in only one eye（10%） treated with topical antibiotics, shallow anterior chamber in two eyes（20%）.CONCLUSION： This study proves that the use of a collagen matrix implant yields equally effective results as MMC when combined with trabeculectomy for the treatment of CG in SWS. Furthermore, OLO implantation is safe and has low incidences of complications.

PIGN mutation multiple congenital anomalies-hypotonia-seizures syndrome 1:A case report

BACKGROUND Multiple congenital anomalies-hypotonia-seizures syndrome 1(MCAHS1)associated with mutations in PIGN gene.CASE SUMMARY The authors report 1 case of a 16 years old girl who was presented with epilepsy,developmental delay and cerebellar atrophy.She harbors a compound heterozygous variant in the PIGN gene,include a nonsense splice site mutation(c.2557A>C)which was inherited from her mother,and a novel site mutation(c.980del)which was inherited from her father.CONCLUSION This case report expands the mutation spectrum found in PIGN gene,and strengthens the association between PIGN mutation and MCAHS1.Mutations in PIGN gene may be an underestimated cause of epilepsy.The authors recommend that,for patients with epilepsy or prenatal diagnosis of highly suspicious fetus,gene sequencing should be the preferred detection method.

A case of 9p deletion syndrome with congenital infantile glaucoma,effective method of diagnosis,and treatment

Dear Editor,I am Dr.Jia X from the Department of Ophthalmology,Second Xiangya Hospital,Central South University,Changsha,China.I write to present a rare case report of 9p deletion syndrome with congenital infantile glaucoma in an infant,accompanying with an effective method of both diagnosis and treatment.

The Notched T Waves Associated With HERG Gene Ala561Val Mutation in Congenital LQT Syndrome

Objectives To study the phenotype of a China LQT family and investigate the relationship of phenotype and gene. Methods The clinical materials were analyzed and gene mutations were screened by sequencing. Results A distinctive biphasic T wave pattern was shown in the left precordial leads of all patients. The LQT2 related HERG gene Ala561Val mutation was found. Conclusions A prolonged QT interval accompanied biphasic T wave indicates HERG mutation.

Experience of a single center with congenital hepatic fibrosis:A review of the literature

Congenital hepatic fibrosis(CHF) is an autosomal recessive inherited malformation defined pathologically by a variable degree of periportal fibrosis and irregularly shaped proliferating bile ducts.It is one of the fibropolycystic diseases,which also include Caroli disease,autosomal dominant polycystic kidney disease,and autosomal recessive polycystic kidney disease. Clinically it is characterized by hepatic fibrosis,portal hypertension,and renal cystic disease.CHF is known to occur in association with a range of both inherited and non-inherited disorders,with multiorgan involvement,as a result of ductal plate malformation.Because of the similarities in the clinical picture,it is necessary to differentiate CHF from idiopathic portal hypertension and early liver cirrhosis,for which a liver biopsy is essential. Radiological tests are important for recognizing involvement of other organ systems.With regards to our experience at Hacettepe University,a total of 26 patients have been diagnosed and followed-up between 1974 and 2009 with a diagnosis of CHF.Presentation with Caroli syndrome was the most common diagnosis,with all such patients presenting with symptoms of recurrentcholangitis and symptoms related to portal hypertension. Although portal fibrosis is known to contribute to the ensuing portal hypertension,it is our belief that portal vein cavernous transformation also plays an important role in its pathogenesis.In all patients with CHF portal vein morphology should be evaluated by all means since portal vein involvement results in more severe and complicated portal hypertension.Other associations include the Joubert and Bardet-Biedl syndromes.

Pulmonary Arterial Hypertension Medical Management of the Adult Patient with Congenital Heart Disease

Congenital heart disease(CHD)-associated pulmonary arterial hypertension(PAH)includes a heterogeneous patient population that can be characterized by the underlying cardiac malformation.CHD-associated PAH has an estimated prevalence of 5– 10% in adult patients,with an increasing number of patients surviving to adulthood because of advances in the surgical management and the development of pulmonary arterial hypertension(PAH)-targeted pharmacotherapy.Although limited data exist,targeted PAH pharmacotherapy has proven to be benefi cial in patients with CHD-associated PAH,with observed improvement in functional class,increase in exercise capacity,and improvement in quality of life and cardiopulmonary hemodynamics.Additionally,there has been increasing interest in the“treat-to-close”strategy.PAH-targeted pharmacotherapy may be used to optimize cardiopulmonary hemodynamics so as to improve patients’operability in repairing the cardiac defect.Although there have been signifi cant advances in the management of this disease state in the past 2 decades,mortality remains high,and ongoing clinical trials are needed to better understand the treat-to-close strategy.

Costello Syndrome with Congenital Pulmonary Valve Stenosis and Ventriculomegaly—A Case Report

Costello syndrome is an extremely rare genetic disorder with growth delay after birth and typically results in short stature during childhood. It is one of the RASopathy of Ras/MAPK pathway syndromes. It affects the transforming protein p21, an enzyme that in humans is encoded by the HRAS gene. H-Ras is a small G protein and once bound to Guanosine triphosphate, it will activate a Raf kinase like C-Raf, the next step in the MAPK/ERK pathway (mitogen-actvated protein kinase/extracellular signal-regulated kinase) i.e., MEK (mitogen-actvated ERK kinase), a protein that phosphorylate ERK which can directly and indirectly activate many transcription factors. This pathway is also known as Ras-Raf, MEK-ERK pathway, which is a chain of proteins on the cell that communicate a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell. Activation of ERK 1/2 is involved in signal transduction pathways associated with cardiac hypertrophy. The developmental syndromes caused by germline mutations in genes that alter the RAS components of the MAP/ERK signal transduction pathway are called “RASopathies”. Cardiovascular abnormalities are important features of Costello syndrome and other RASopathies such as Noonan syndrome. Background of this case report described the congenital valvular pulmonic stenosis and ventriculomegaly associated with Costello syndrome by transthoracic echocardiographic imaging in a 9-year-old male boy.

Ductal paucity and Warkany syndrome in a patient with congenital extrahepatic portocaval shunt

An eleven-year-old clinically dysmorphic and devel-opmentally retarded male child presenting with com-plaints of 5 episodes of recurrent cholestatic jaundice since 3 years of age was evaluated. Imaging revealed features consistent with congenital extrahepatic porto-caval shunt(Abernethy type 1b), multiple regenerative liver nodules and intrahepatic biliary radical dilatation. The presence of ductal paucity and trisomy 8 were con-firmed on liver biopsy and karyotyping. The explanation for unusual and previously unreported features in the present case has been proposed.

The effectiveness and safety of thyroxine replacement therapy for children with down syndrome and subclinical or congenital hypothyroidism—A systematic review

Introduction: Down syndrome (DS) is the most common chromosomal abnormality causing mental handicap in humans. Children with DS have significant medical problems and developmental delay which are further impaired by hypothyroidism. Those clinical features are potentially improved by using thyroxine replacement therapy. Objectives: To examine the evidence of effectiveness (motor & mental development) and safety of thyroxine supplementation in the treatment of SH and CH in children with DS. Methods: Several medical data bases (MEDLINE, EMBASE, CINAHL, Cochrane, Clinical Trials Gov, Essential Evidence and Google) were searched until 20 October, 2011, for randomized control trials (RCTs) that had examined thyroxine’s effectiveness and safety in the treatment of SH or CH in children with DS. Results: There were two high quality RCTs that examined thyroxine in the treatment of CH in children with DS, and no RCTs were found to have examined the effectiveness of thyroxine for SH in children with DS. Conclusion: The RCT which met our inclusion criteria provides the reliable evidence in recommending thyroxine for the treatment of CH in children with DS which is similar to the guidelines for general population. The absence of RCTs examining the treatment of SH in Children with DS indicates the need to conduct such trials.

Kabuki-Syndrome and Congenital Heart Disease-A Twenty-Year Institutional Experience

Background:Patients with genetic syndromes who undergo surgery to correct congenital heart defects can be at risk for increased morbidity or mortality.Surgical outcomes and postoperative courses following congenital heart surgery in patients with Kabuki-Syndrome(KS)have not been well studied.Objectives:The purpose of this study was to describe the postoperative courses and associated outcomes in the largest set of KS patients undergoing congenital heart surgery to date.Methods:Patients with a confirmed molecular diagnosis of KS and a diagnosis of a CHD admitted to Texas Children’s Hospital between January 1,2000 and January 1,2020 were included(n=20).Demographics and medical histories were collected from the hospitals’electronic health records.Results:Of 20 patients identified with KS and a CHD,15 required surgical correction of their congenital cardiac malformation.Median age and weight at the time of surgery was 2 months and 4.1 kg,respectively.Median duration of hospital stay was 49 days for all surgeries and 151 days for the Norwood procedure.Postoperative infections and pleural effusions were detected and treated in 45.8%and 50%of patients,respectively.There was no in-hospital mortality for any surgery.Median follow up time was 5.6 years;survival at 6 years was 94%.Conclusions:Although KS patients seem to be at increased risk for a more complicated,prolonged postoperative course than that of patients without a genetic syndrome,patients with a diagnosis of a CHD and KS do not appear to be at increased risk of mortality following congenital heart surgery.

Ascites of Great Abundance Revealing a Nephrotic Congenital Syndrome at the University Teaching Hospital of Bouaké: About a Case

Congenital nephrotic syndrome (CNS) is defined as the presence of proteinuria > 50 mg/kg/24h associated with a protein concentration g/L or albuminemia 30 g/L in an infant less than 3 months old. The CNS is rare, of various clinical forms dominated by the Finnish type caused by a mutation of the NPHS1 gene located on chromosome 19. The edematous syndrome is the most common mode of discovery. We report a case discovered in an infant of 50 days admitted for ascites of great abundance. The aim of this study was to describe the main epidemiological, diagnostic, therapeutic and evolutionary aspects of this syndrome. Improving the prognosis of this condition requires advocacy with the political authorities of Cote d’Ivoire to provide Teaching Hospital for the resources needed to perform kidney transplantation.

Multiple Major Thrombo-Embolic Events, including Stroke, in a Patient with Combined Congenital Anti-Thrombin III Deficiency and MTHFR Homozygous Mutation

We report a case of a young male patient suffering from congenital Anti-Thrombin III (AT III) deficiency, presented with four major thrombotic events. These events were acute coronary syndrome (Non-ST elevation myocardial infarction), cerebral infarction, peripheral acute upper limb (UL) ischemia and bilateral extensive deep venous thrombosis. The latter two developed despite that the patient was receiving full anticoagulation therapy. His International normalized ratio (INR) was 2.5. Eventually, the patient developed pulmonary embolism and died. He had a prominent family history of thrombotic events. Screening for AT III deficiency in young patients with thrombotic event (thrombophilia) is essential especially those having family history of the latter. This is justified as thrombotic events may occur in up to 80% of these patients. Our patient with 4 major thrombotic events ending in fatality in less than 1 month deserves the nomenclature.

Prediction of Pulmonary Arterial Pressure Level after Repair of Congenital Cardiac Communications and Discharge from the Hospital: Role of Down Syndrome and Early Postoperative Hemodynamics

Background:Postoperative pulmonary hypertension limits the success of surgical treatment in some patients with unrestrictive congenital cardiac communications.Identifying patients at risk of developing postoperative pulmonary hypertension is important to individualize follow-up strategies.Methods:We analyzed a prospective cohort of 52 pediatric patients(age 3 to 35 months)looking for perioperative predictors of mildly elevated pulmonary arterial pressure 6 months after surgery,defined as a systolic pressure greater than 30 mmHg by transthoracic echocardiography.This corresponds to a mean pulmonary arterial pressure of>20 mmHg.Clinical,echocardiographic and hemodynamic parameters were investigated.Perioperative hemodynamics was assessed by directly measuring pulmonary and systemic arterial pressures using indwelling catheters.Early postoperative pulmonary hemodynamics was defined as the mean pulmonary/systemic mean arterial pressure ratio(PAP/SAP)obtained per patient during the first 6 h of postoperative care.Results:Among the factors that were investigated as possible predictors,perioperative hemodynamics and the presence of Down syndrome were initially selected using univariate analysis(p<0.030).Early postoperative PAP/SAP was correlated with PAP/SAP obtained in the operating room just after cardiopulmonary bypass(r=0.70,p<0.001),and it was higher in subjects with Down syndrome than in nonsyndromic individuals(p=0.003).Early postoperative PAP/SAP was the only predictor selected using multivariate analysis.It was characterized as an independent predictor after adjustments for possible confounders.An early postoperative PAP/SAP of>0.35 was 76%sensitive and 74%specific at predicting a systolic pulmonary arterial pressure of>30 mmHg 6 months after surgery(hazard ratio with 95%CI 8.972[2.428–33.158],p=0.002).Conclusion:The hypertensive early postoperative behavior of the pulmonary circulation was strongly but not exclusively associated with Down syndrome,and it was characterized as an independent predictor of altered pulmonary arterial pressure after discharge from the hospital.

Identification of a novel mutation in the FGF10 gene in a Chinese family with obvious congenital lacrimal duct dysplasia in lacrimo-auriculo-dento-digital syndrome

AIM:To identify the pathogenic gene variant in a family with lacrimo-auriculo-dento-digital syndrome[LADD(MIM 149730)]showing congenital lacrimal duct dysplasia as the main clinical manifestation and lay the foundation for future research on the pathogenic gene.METHODS:Ophthalmological examinations,including slit-lamp biomicroscopy and lacrimal duct probing,and computed tomography dacryocystography(CT-DCG)were performed for all participants.The family pedigree was drawn,genetic features were analyzed,and the genomic DNA of the subjects was extracted.Pathogenic genes were screened via whole exome sequencing(WES)and confirmed using Sanger sequencing.RESULTS:Six patients belonged to this three-generation family,and their clinical manifestations included congenital nasolacrimal duct obstruction,congenital absence of lacrimal puncta and canaliculi,lacrimal fistulae,and limb deformities.This pattern indicates autosomal dominant inheritance.Diagnosis was based on the clinical characteristics of LADD syndrome,which presented in all the patients in this family.A novel frameshif t mutation in the FGF10 gene(NM_004465.1),c.234dup C(p.Trp79Leus*15),was identified in all patients via WES.The variant was confirmed by Sanger sequencing and classified as a“pathogenic mutation”according to the American College of Medical Genetics and Genomics(ACMG)variant interpretation guidelines.CONCLUSION:A novel frameshift mutation in the FGF10 gene is found in all patients.This finding helps this family with LADD syndrome receiving a more accurate clinical diagnosis and genetic counseling by extending the mutation range of the FGF10 gene.

Turner syndrome with positive SRY gene and non-classical congenital adrenal hyperplasia: A case report

BACKGROUND Co-morbidity of SRY gene turner syndrome(TS)with positive SRY gene and nonclassical congenital adrenal hyperplasia(NCAH)is extremely rare and has never been reported to date.CASE SUMMARY In this article,we present a 14-year-old girl who was referred to our hospital with short stature(weight of 43 kg and height of 143 cm,<-2 SD)with no secondary sexual characteristics(labia minora dysplasia).Laboratory tests indicated hypergonadotropic hypogonadism with significantly increased androstenedione and 17-hydroxyprogesterone(17-OHP)levels.This was accompanied by the thickening of the extremity of the left adrenal medial limb.The patient’s karyotype was 45,X/46,X,+mar,and cytogenetic analysis using multiplex ligation-dependent probe amplification and high-throughput sequencing indicated that the SRY gene was positive with compound heterozygous mutations in CYP21A2 as the causative gene for congenital adrenal hyperplasia.The sites of the suspected candidate mutations were amplified and verified using Sanger sequencing.The patient was finally diagnosed as having SRY positive TS with NCAH.The patient and her family initially refused medical treatment.At her most recent follow-up visit(age=15 years old),the patient presented facial hair,height increase to 148 cm,and weight of 52 kg,while androstenedione and 17-OHP levels remained high.The patient was finally willing to take small doses of hydrocortisone(10 mg/d).CONCLUSIONIn conclusion, upon evaluation of the patient mentioned in the report, we feel that17-OHP measurement and cytogenetic analysis are necessary for TS patients evenin the absence of significant virilization signs. This will play a significant role inguiding diagnosis and treatment.

Unique Roberts syndrome with bilateral congenital glaucoma: A case report

BACKGROUND Congenital glaucoma associated with Roberts syndrome(RS)is an unusual and unique condition.No previous report describes this association.A multidisciplinary approach including molecular studies were conducted to reach the final diagnosis.CASE SUMMARY We present a rare case of a 1-wk-old male with RS associated with bilateral congenital glaucoma,left ectopic kidney,and left-hand rudimentary digits.A comprehensive approach was applied by which bilateral non-penetrating glaucoma surgery was performed with good control of intraocular pressure for more than 6 mo.Cytogenetic and molecular testing were conducted and revealed normal measurements.CONCLUSION This report described a case of a male baby with clinical features of RS but with a negative molecular analysis,presenting with left-hand rudimentary digits,bilateral congenital glaucoma,and left ectopic kidney.To the best of our knowledge,this is the first case reported with phocomelia,bilateral congenital glaucoma,and unilateral ectopic kidney.

Moyamoya Syndrome in Post-Transplant Children with Type 1 Neurofibromatosis and Congenital Nephrotic Syndrome

Background: Neurofibromatosis (NF) is a genetic disorder of the nervous system that affects the development and growth of neuronal tissues. It is characterized by the development of malignant and benign tumors of the peripheral nerves and meningiomas, and the clinical manifestations can vary, including cerebral vascular compromise that precipitates symptoms characteristic of Moyamoya syndrome. The behavior of a posttransplant child with type 1 NF who presents with characteristics of Moyamoya syndrome and is a carrier of a WT1 genetic mutation is unknown, which is why the report was made. Case Report: A child with type I NF with a history of cryptorchidism, hypospadias, bilateral sensorineural hearing loss, and chronic renal failure was arising from a congenital nephrotic syndrome due to a WT1 gene mutation at 3 years of age began renal replacement therapy initially with chronic ambulatory peritoneal dialysis and hemodialysis for refractory peritonitis. He underwent two episodes of transient ischemic attack (TIA) characterized by right hemiparesis during hemodialysis therapy and during six months post-kidney transplantation present a similar episode. Studies for other causes were negative, and imaging studies show characteristics of NF-related vasculitis, cortical lesions, and focal lesions in the left frontal subcortical white matter with annular enhancement and subcortical edema in the parasagittal region of the left parietal lobe, as well as a decrease in flow in the cortical branches of the middle cerebral artery were described. After four weeks, the clinical manifestations of hemiparesis completely disappeared without leaving any sequels continuing with the regular immunosuppression of the everolimus, mycophenolate and low dose steroids. Conclusion: These findings are suggestive of small and mediumsized vessel vasculitis compatible with Moyamoya syndrome in child post-transplantation associated with arteriopathy by NF.

A Missense Mutation in Epsilon-subunit of Acetylcholine Receptor Causing Autosomal Dominant Slow-channel Congenital Myasthenic Syndrome in a Chinese Family

Background：Congenital myasthenic syndromes are a group orrare disorders that are clinically and genetically heterogeneous and caused by mutations in the genes encoding proteins of the neuromuscular junction.Here,we described a Chinese family that presented with phenotypes of classic slow-channel congenital myasthenic syndrome （SCCMS）.Methods：Clinical characteristics and electrophysiological features of three patients from a Chinese family were examined,and next-generation sequencing followed by direct sequencing was carried out.Results：The patients revealed variability in clinical and electrophysiological features.However,weakness,scoliosis,and repetitive-compound muscle action potential were found in all affected members in the family.A heterozygous C〉T missense mutation at nucleotide 865 in acetylcholine receptor epsilon-subunit （CHRNE） gene that causes a leucine-to-phenylalanine substitution at position 289 （L289F） was found.Conclusions：We reported a SCCMS family of Chinese origin.In the family,classical clinical phenotype with phenotypic variability among different members was found.Genetic testing could help diagnose this rare disease.

A Novel AGRN Mutation Leads to Congenital Myasthenic Syndrome Only Affecting Limb？girdle Muscle

Background： Congenital myasthenic syndromes （CMSs） are a group of clinically and genetically heterogeneous disorders caused by impaired neuromuscular transmission. The defect of AGRN was one of the causes of CMS through influencing the development and maintenance of neuromuscular transmission. However, CMS reports about this gene mutation were rare. Here, we report a novel homozygous missense mutation （c.5302G〉C） of AGRN in a Chinese CMS pedigree. Methods： We performed a detailed clinical assessment of a Chinese family with three affected members. We screened for pathogenic mutations using a disease-related gene panel containing 519 genes associated with genetic myopathy （including 17 CMS genes）. Results： In the family, the proband showed limb-girdle pattern of weakness with sparing of ocular, facial, bulbar, and respiratory muscles. Repetitive nerve stimulation showed a clear decrement of the compound muscle action potentials at 3 Hz only. Pathological analysis of the left tibialis anterior muscle showed predominance of type I fiber and the presence of scattered small angular fibers. The proband＇s two elder sisters shared a similar but more severe phenotype. By gene analysis, the same novel homozygous mutation （c.5302G〉C, p.A1768P） of AGRN was identified in all three affected members, whereas the same heterozygous mutation was found in both parents, revealing an autosomal recessive transmission pattern. All patients showed beneficial responses to adrenergic agonists. Conclusions： This study reports a Chinese pedigree in which all three children carried the same novel AGRN mutation have CMS only affecting limb-girdle muscle. These findings might expand the spectrum of mutation in AGRN and enrich the phenotype of CMS.