22q11 Microdeletion Syndrome Research Articles

The first case of hyperosmolar diabetic ketoacidosis in a patient diagnosed with MODY 5 (maturity-onset diabetes of the young type 5) and 17q12 microdeletion syndrome.

The first case of hyperosmolar diabetic ketoacidosis in a patient diagnosed with MODY 5 (maturity-onset diabetes of the young type 5) and 17q12 microdeletion syndrome.

Prenatal diagnosis and family analysis of 17q12 microdeletion syndrome with fetal renal abnormalities.

To analyze the prenatal diagnosis, parental verification, and pregnancy outcomes of three fetuses with 17ql2 microdeletion syndrome. We retrospectively reviewed 46 singleton pregnancies with anomalies in the urinary system who underwent amniocentesis from Feb 2022 to October 2023 in the Prenatal Diagnosis Center of Lianyungang Maternal and Child Health Hospital. These fetuses were subjected to chromosomal microarray analysis (CMA) and/or trio whole-exome sequencing (Trio-WES). We specifically evaluated these cases' prenatal renal ultrasound findings and clinical characteristics of the affected parents. Three fetuses were diagnosed as 17q12 microdeletions, and the detection rate was 6.5% in fetuses with anomalies in the urinary system (3/46). The heterogeneous deletions range from 1.494 to 1.66Mb encompassing the complete hepatocyte nuclear factor 1 homeobox B (HNF1B) gene. Fetuses with 17q12 deletion exhibited varied renal phenotypes. Moreover, the clinical phenotypes of the affected parents differed greatly in the two cases (case 2 and case 3) in which the deletion was inherited. For case 3, the mother manifested classic symptoms of 17q12 deletion syndrome as well as unreported characteristics, such as very high myopia. Our findings demonstrate the necessity and significance of offering prenatal genetic testing when various renal anomalies are detected. In addition, our study broadens the phenotypic spectrum of 17q12 deletions. Most importantly, our findings may allow timely supportive genetic counseling and guidance for pregnancy in affected families, e.g., with the help of preimplantation genetic testing (PGT).

Hypersensitivity to Psychotropic Medications in a Patient With 17q12 Microdeletion Syndrome: A Case Report.

Hypersensitivity to Psychotropic Medications in a Patient With 17q12 Microdeletion Syndrome: A Case Report.

Severe Hypocalcemia in the Adolescent as the Only Manifestation of <i>22q11</i> Microdeletion Syndrome: Clinical Case

Background. In this article, we would like to describe the atypical clinical picture and course of 22q11 microdeletion syndrome in a patient without specific phenotypic signs and symptoms typical for this disease.Clinical case description. Male patient, 13 years old, was hospitalized for the first time with seizure and multiple spinal fractures caused by hypocalcemia. He was referred to rheumatologist and clinical geneticist after hospital stay. Differential diagnosis included not only various bones metabolic diseases, but also 22q11 deletion syndrome. Later it was confirmed via FISH test.Conclusion. This clinical case proves once again the uniqueness of every single case, as well as the importance of comprehensive approach to the diagnosis and management of such patients.

Clinical and genetic analysis of a fetus with 17q12 microdeletion syndrome

To explore the clinical phenotype and genetic characteristics of a fetus with 17q12 microdeletion syndrome. A fetus with 17q12 microdeletion syndrome who was diagnosed at Huzhou Maternal & Child Health Care Hospital in June 2020 was selected as the study subject. Clinical data of the fetus was collected. The fetus was subjected to chromosomal karyotyping and chromosomal microarray analysis (CMA). To determine the origin of fetal chromosomal abnormality, its parents were also subjected to CMA assay. The postnatal phenotype of the fetus was also investigated. Prenatal ultrasound revealed polyhydramnios and fetal renal dysplasia. The fetus was found to have a normal chromosomal karyotype. CMA has detected a 1.9 Mb deletion in the 17q12 region, which has encompassed five OMIM genes including HNF1B, ACACA, ZNHIT3, CCL3L1 and PIGW. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the 17q12 microdeletion was predicted as pathogenic copy number variation (CNV). CMA analysis has detected no pathogenic CNV in both parents. After birth, the child was found to have renal cysts and abnormal brain structure. Combined with the prenatal findings, the child was diagnosed with 17q12 microdeletion syndrome. The fetus has 17q12 microdeletion syndrome presenting as abnormalities of the kidney and central nervous system, which are strongly correlated with functional defects of the deletion region involving the HNF1B and other pathogenic genes.

EEG Findings in a Pediatric Patient with 3q29 Microdeletion Syndrome (P13-1.005)

<h3>Objective:</h3> 3q29 microdeletion syndrome is a rare genetic disorder which results from interstitial microdeletion of a segment on the long arm of chromosome 3. The syndrome is characterized by neurodevelopmental and psychiatric manifestations including intellectual disability, autism spectrum disorder, anxiety, executive function deficits, and psychosis/schizophrenia. Systemic manifestations include ocular issues, gastrointestinal disorders, dental anomalies, and congenital heart defects. <h3>Background:</h3> We present a 7-year-old boy with a history of intellectual disability including delayed speech and fine motor abilities, and autism spectrum disorder, who presented with frequent and new onset of complete behavioral arrest, staring, grunting and pulling movements lasting several minutes that were described by his teachers. Spells did not progress to tonic-clonic activity and were not associated with urine loss. His physical examination revealed down slanted eyes, epicanthal folds, wide mouth, long and thin philtrum, thin upper lip and axial and appendulicar tone were decreased. EEG while off ASM revealed excessive beta activity of the background, frontally dominant generalized spike/polyspike and wave discharges, and focal spike/polyspike and wave activity seen independently over the left and right frontocentral regions. MRI showed reduced cerebral white matter hemispheric volume involving the frontoparietal lobes with no obvious seizure focus. He was subsequently started on levetiracetam, which resulted in a cessation of staring spells. <h3>Design/Methods:</h3> NA <h3>Results:</h3> NA <h3>Conclusions:</h3> Seizures have been reported in 13% of patients with 3q29 microdeletion syndrome and are generally mild and responsive to ASM. Previously reported EEG abnormalities in patients with 3q29 microdeletion syndrome include focal epileptiform discharges in the left occipital region and slow waves in the frontotemporal regions. To our knowledge, generalized spike/polyspike wave activity has not previously been reported in this syndrome. Whether the independent focal frontocentral epileptiform discharges represent a forme fruste of the generalized discharges, or the latter represent a rapid secondary bisynchrony phenomenon, remains to be determined. <b>Disclosure:</b> Dr. Sheikh has nothing to disclose. Dr. Nascimento has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Zogenix. The institution of Dr. Nascimento has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biocodex. Dr. Nascimento has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for AAN. The institution of Dr. Nascimento has received research support from Zogenix. The institution of Dr. Nascimento has received research support from Biocodex. The institution of Dr. Nascimento has received research support from Greenwich. Dr. Nascimento has received publishing royalties from a publication relating to health care. Dr. Nascimento has a non-compensated relationship as a Editorial Team Member with Neurology RFS that is relevant to AAN interests or activities. Dr. Nascimento has a non-compensated relationship as a Production Team with Neurology Podcast that is relevant to AAN interests or activities. Dr. Waite has nothing to disclose. Dr. Lam has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sage Therapeutics. Dr. Lam has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurona Therapeutics. Dr. Lam has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Cognito Therapeutics. The institution of Dr. Lam has received research support from Sage Therapeutics.

Prenatal diagnosis in the fetal hyperechogenic kidneys: assessment using chromosomal microarray analysis and exome sequencing

Fetal hyperechogenic kidneys (HEK) is etiologically a heterogeneous disorder. The aim of this study was to identify the genetic causes of HEK using prenatal chromosomal microarray analysis (CMA) and exome sequencing (ES). From June 2014 to September 2022, we identified 92 HEK fetuses detected by ultrasound. We reviewed and documented other ultrasound anomalies, microscopic and submicroscopic chromosomal abnormalities, and single gene disorders. We also analyzed the diagnostic yield of CMA and ES and the clinical impact the diagnosis had on pregnancy management. In our cohort, CMA detected 27 pathogenic copy number variations (CNVs) in 25 (25/92, 27.2%) fetuses, with the most common CNV being 17q12 microdeletion syndrome. Among the 26 fetuses who underwent further ES testing, we identified 7 pathogenic/likely pathogenic variants and 8 variants of uncertain significance in 9 genes in 12 fetuses. Four novel variants were first reported herein, expanding the mutational spectra for HEK-related genes. Following counseling, 52 families chose to continue the pregnancy, and in 23 of them, postnatal ultrasound showed no detectable renal abnormalities. Of these 23 cases, 15 had isolated HEK on prenatal ultrasound. Taken together, our study showed a high rate of detectable genetic etiologies in cases with fetal HEK at the levels of chromosomal (aneuploidy), sub-chromosomal (microdeletions/microduplications), and single gene (point mutations). Therefore, we speculate that combined CMA and ES testing for fetal HEK is feasible and has good clinical utility. When no genetic abnormalities are identified, the findings can be transient, especially in the isolated HEK group.

Identification of 17q12 microdeletion syndrome in a Latin American patient with maturity-onset diabetes of the young subtype 5: a case report

BackgroundMaturity-onset diabetes of the young comprises a large group of autosomal inherited gene mutations. Maturity-onset diabetes of the young subtype 5 is caused by mutations in the HNF1B gene. This gene is expressed in the early phase of embryonic development in the pancreas, kidneys, liver, and genital tract; therefore, kidney or urinary tract malformations are associated with diabetes mellitus. The 17q12 deletion syndrome is a cause of maturity-onset diabetes of the young subtype 5 that should be considered.Case presentationWe present the case of a 35-year-old Hispanic female patient with a history of bicornuate uterus and polycystic renal disease that required kidney transplant. She had insulin-dependent diabetes, with her mother, maternal grandmother, and great-grandmother showing a similar clinical manifestation. Molecular analysis showed a deletion in chromosome 17q12 involving 15 genes, including HNF1B. Therefore, a diagnosis of deletion syndrome was made.ConclusionsThe 17q12 deletion syndrome represents a rare genetic syndrome that involves different genes, including HNF1B. Principally, it is characterized by the combination of genitourinary tract malformations and diabetes mellitus, similar to our patient.

Review of neurodevelopmental disorders in patients with HNF1B gene variations.

This review investigates the association between neurodevelopmental disorders (NDD) and variations of the gene HNF1B. Heterozygous intragenetic mutations or heterozygous gene deletions (17q12 microdeletion syndrome) of HNF1B are the cause of a multi-system developmental disorder, termed renal cysts and diabetes syndrome (RCAD). Several studies suggest that in general, patients with genetic variation of HNF1B have an elevated risk for additional neurodevelopmental disorders, especially autism spectrum disorder (ASD) but a comprehensive assessment is yet missing. This review provides an overview including all available studies of patients with HNF1B mutation or deletion with comorbid NDD with respect to the prevalence of NDDs and in how they differ between patients with an intragenic mutation or 17q12 microdeletion. A total of 31 studies was identified, comprising 695 patients with variations in HNF1B, (17q12 microdeletion N = 416, mutation N = 279). Main results include that NDDs are present in both groups (17q12 microdeletion 25.2% vs. mutation 6.8%, respectively) but that patients with 17q12 microdeletions presented more frequently with any NDDs and especially with learning difficulties compared to patients with a mutation of HNF1B. The observed prevalence of NDDs in patients with HNF1B variations seems to be higher than in the general population, but the validity of the estimated prevalence must be deemed insufficient. This review shows that systematical research of NDDs in patients with HNF1B mutations or deletions is lacking. Further studies regarding neuropsychological characteristics of both groups are needed. NDDs might be a concomitant of HFN1B-related disease and should be considered in clinical routine and scientific reports.

17q12 Microdeletion Syndrome as a Rare Cause of Elevated Liver Enzymes: Case Report and Literature Review

17q12 deletion syndrome is a rare autosomal dominant inherited condition. It results from de novo mutation and can occur without a family history. Hepatocyte nuclear factor-1 beta (HNF1B) and LIM homeobox 1 (LXH1) genes are the most common genes to be deleted in this syndrome. It has unique clinical characteristics involving multiple systems in the body. The most common presentations are usually renal involvement and maturity-onset diabetes of the young type 5 (MODY5). Genetic study is the golden tool to diagnose patients with this syndrome. Our case presents the unique clinical features of 17q12 deletion syndrome along with a literature review.

Prenatal diagnosis of two fetuses with 17q12 microdeletion syndrome

To explore the genetic etiology of two fetuses with 17q12 microdeletion syndrome. Chromosomal karyotype analysis, whole exome sequencing (WES) and chromosomal microarray analysis (CMA) were carried out for the fetuses. Relevant literature was searched in databases such as CNKI, Wanfang and PubMed to summarize the prenatal ultrasound finding, pregnancy outcome and clinical phenotype of the syndrome. Both fetuses were found have renal parenchymal echo enhancement, accompanied by presence of renal cysts or hydramnios. Both were found to have a normal chromosomal karyotype, but had a 17q12 microdeletion by WES and CMA analysis. A total of 433 cases of 17q12 microdeletion syndromes have been reported in the literature, with renal cysts and diabetes as the most common phenotypes. Among 240 fetuses diagnosed with this syndrome, 72.9% showed unilateral or bilateral renal parenchymal echo enhancement, and 23.3% showed unilateral or bilateral renal cysts. Among these, 68 had reported the pregnancy outcome, for which 70.5% of pregnant women had opted termination of the pregnancy. WES and CMA can effectively detect 17q12 microdeletion. The clinical manifestations of this syndrome mainly include enhanced renal parenchymal echo, renal cyst, kidney disease and early-onset diabetes. Upon prenatal consultation, the prognosis of the fetus should be fully informed, and advice should be provided in combination with the preference of the couple, pregnancy history, family condition and other aspects.

Prenatal ultrasound features and genetic analysis for 17q12 microdeletion syndrome.

The 17q12 microdeletion syndrome is a type of syndrome caused by a deletion of 1.4 to 1.8 Mb in the 17q12 region of the chromosome. The main clinical features of the syndrome are structural or functional abnormalities in the kidney and urethra, type 5 diabetes, and neurodevelopmental or neuropsychiatric disorders. The diverse range of phenotypes associated with 17q12 microdeletion limited clinical recognition and diagnosis. In addition, the phenotypic description of this microdeletion is mainly about postpartum. Due to the rarity of the 17q12 microdeletion itself, studies on the prenatal phenotype of the 17q12 microdeletion are limited. This study aims to analyze the prenatal ultrasound features of 17q12 microdeletion, and to investigate the possibility of genotype-phenotype relationship for providing evidence for genetic counseling in such pregnancies. A total of 3 320 pregnant women and their fetuses were collected for the detection of chromosome copy number variation sequencing (CNV-Seq) due to different ultrasound anomalies in Xiangya Hospital of Central South University. The clinical data of pregnant women and their fetuses who were found to harbor 17q12 microdeletion were reviewed, including maternal age, fetus ultrasound findings, gestational week of the invasive procedure, CNV-Seq results, and the pregnancy outcome. CNV-Seq was tested in the parents to verify whether the abnormality was de novo or inherited. The prenatal ultrasound features and CNV-Seq test results of these 12 fetuses were analyzed and their pregnancy outcomes were followed up. Approximately 0.36% (12/3 320) of fetuses were detected to have 17q12 microdeletion, all characterized as renal abnormalities, accounting for 4.2% (12/288) of all prenatal ultrasound with renal abnormalities, accounting for 48% (12/25) of prenatal ultrasound with renal abnormalities and pathogenic chromosomal abnormalities. The sizes of 17q12 deletion ranged from 1.4 to 1.7 Mb, and all of them included the HNF1B gene. Nine cases were de novo, 2 inherited from the mother, and 1 inherited from father. Among 12 fetuses with 17q12 deletion, 11 cases of prenatal ultrasound suggested bilateral hyperechogenic kidneys and 1 case only showed renal cyst, in which 3 fetuses with enlarged kidneys, 1 with clubfeet, and 1 with subependymal cyst. Pregnancy outcomes were available for 11 of the 12 fetuses. Of them, the parents of 9 fetuses with de novo deletion chose to terminate the pregnancy, and 2 live birth babies inherited from their mother with normal renal function had persistent renal echogenicity enhancement after birth. Bilateral hyperechogenic kidneys show strikingly correlation with 17q12 microdeletion, suggesting the necessity of chromosome copy numbers detection for fetuses with hyperechogenic kidneys.

Molecular and phenotypic characteristics of 15q24 microdeletion in pediatric patients with developmental disorders

Chromosome 15q24 microdeletion is a rare genetic disorder characterized by development delay, facial dysmorphism, congenital malformations, and occasional autism spectrum disorder (ASD). In this study, we identified five cases of 15q24 microdeletion using multiplex ligation-dependent probe amplification (MLPA) technology in a cohort of patients with developmental delay and/or intellectual disability. Two of these five cases had deletions that overlapped with the previously defined 1.1 Mb region observed in most reported cases. Two cases had smaller deletions (< 0.57 Mb) in the 15q24.1 low copy repeat (LCR) B-C region. They presented significant neurobehavioral features, suggesting that this smaller interval is critical for core phenotypes of 15q24 microdeletion syndrome. One case had minimal homozygous deletion of less than 0.11 Mb in the 15q24.1 LCR B-C region, which contained CYP1A1 (cytochrome P450 family 1 subfamily A member 1) and EDC3 (enhancer of mRNA decapping 3) genes, resulting in poor immunity, severe laryngeal stridor, and lower limbs swelling. This study provides additional evidence of 15q24 microdeletion syndrome with genetic and clinical findings. The results will be of significance to pediatricians in their daily practice.

Translatable pathways classification (TransPath-C) for inferring processes germane to human biology from animal studies data: example application in neurobiology.

How to translate insights gained from studies in one organismal species for what is most likely to be germane in another species, such as from mice to humans, is a ubiquitous challenge in basic biology as well as biomedicine. This is an especially difficult problem when there are few molecular features that are obviously important in both species for a given phenotype of interest. Neuropathologies are a prominent realm of this complication. Schizophrenia is complex psychiatric disorder that affects 1% of the population. Many genetic factors have been proposed to drive the development of schizophrenia, and the 22q11 microdeletion (MD) syndrome has been shown to dramatically increase this risk. Due to heterogeneity of presentation of symptoms, diagnosis and formulation of treatment options for patients can often be delayed, and there is an urgent need for novel therapeutics directed toward the treatment of schizophrenia. Here, we present a novel computational approach, Translational Pathways Classification (TransPath-C), that can be used to identify shared pathway dysregulation between mouse models and human schizophrenia cohorts. This method uses variation of pathway activation in the mouse model to predict both mouse and human disease phenotype. Analysis of shared dysregulated pathways called out by both the mouse and human classifiers of TransPath-C can identify pathways that can be targeted in both preclinical and human cohorts of schizophrenia. In application to the 22q11 MD mouse model, our findings suggest that PAR1 pathway activation found upregulated in this mouse phenotype is germane for the corresponding human schizophrenia cohort such that inhibition of PAR1 may offer a novel therapeutic target.

Prenatal ultrasonic characteristics and genetic analysis of fetuses with chromosome 22q11 microdeletion syndrome

To analyze the prenatal ultrasonic characteristics and genetic features of 14 fetuses with chromosome 22q11 microdeletion syndrome (22q11DS). 4989 fetuses were analyzed by using single nucleotide polymorphism array (SNP array) in the Fujian Maternal and Child Health Hospital from November 2016 to November 2019. SNP array showed that 11 fetuses had classic 3 Mb microdeletion in 22q11 region, one fetus had 2.0 Mb microdeletion, and two fetuses had 1.0 Mb microdeletion. The 1.0 Mb microdeletion in 22q11 region contains SNAP29 and CRKL genes, which may increase the risk of congenital renal malformation and cardiovascular malformation. Prenatal ultrasonic characteristics of fetuses with 22q11 microdeletion syndrome vary, and SNP array is a powerful tool to diagnose such diseases, which can provide accurate genetic diagnosis and enable prenatal diagnosis.

Prenatal diagnosis and genetic analysis of two fetuses with paternally derived 17q12 microdeletions

To reported on two fetuses diagnosed with 17q12 microdeletion syndrome. The two fetuses were respectively found to have renal abnormalities and polyhydramnios upon second and third trimester ultrasonography. Umbilical cord blood of the first fetus and amniotic fluid of the second fetus were subjected to single nucleotide polymorphism array (SNP-array) analysis. After 17q12 microdeletion was found in the first fetus, SNP-array was carried out on peripheral blood samples of the parents to determine its origin. With the medical history of the parents taken into consideration, the father underwent high-throughput sequencing for 565 urinary system-related genes to exclude pathogenic or likely pathogenic variants associated with congenital malformations of the urinary and reproductive systems. In both fetuses, SNP-array has revealed a 1.42 Mb deletion at 17q12, or arr[hg19]17q12 (34 822 465-36 243 365) × 1. In both cases the microdeletion was inherited from the father, in whom no urinary disease-related pathogenic or likely pathogenic variants was identified. Paternally derived 17q12 microdeletions probably underlay the genetic etiology of the two fetuses with renal ultrasound abnormalities and polyhydramnios. SNP-array can enable the diagnosis and facilitate genetic counseling and prenatal diagnosis for the families.

Usefulness of copy number variant detection following monogenic disease exclusion in prenatal diagnosis

AimFamilies with an adverse history of monogenic disease focus on single‐gene diagnosis instead of low‐depth whole‐genome sequence, during subsequent pregnancies. The aim of this study was to assess the potential usefulness of low‐depth whole‐genome sequencing (copy number variant sequencing [CNV‐seq]) detection following monogenic disease exclusion in prenatal diagnosis.MethodsA total of 285 families with a history of monogenic disease (of 41 different types; eliminated during the current pregnancy) were recruited and retrospectively analyzed. Low‐depth whole‐genome sequencing (CNV‐Seq, Next‐Seq CN500 platform) was performed for all fetuses.ResultsThe CNV detection results of the 285 samples were as follows: one case of 18‐trisomy chimera (0.35%), one case of pathogenic 3q29 microdeletion syndrome CNV (0.35%), four cases of variant of uncertain significance (VUS) CNVs (1.40%), and four cases of Duchenne muscular dystrophy (DMD) carriers (1.40%); and the remaining samples were normal (96.15%). Of note, 2/285 (0.70%) samples still exhibited pathogenic abnormalities. All positive samples were followed up where the two cases of pathogenic abnormalities elected the pregnancy termination, while the four VUS cases and four DMD‐carrier cases were born healthy.ConclusionIn cases where prenatal fetal monogenic disease has been ruled out, CNV detection is still beneficial and should be performed to prevent missed pathogenic CNVs. However, the costs need to be balanced against benefits, and the research will need to assess other types of testing.

Outcome after surgery for pulmonary atresia with ventricular septal defect, a long-term follow-up study.

AimTo study the long‐term outcome after surgery for pulmonary atresia and ventricular septal defect (PA‐VSD), and to determine association between the contribution of major aorto‐pulmonary collateral arteries (MAPCAs) to the pulmonary blood flow, comorbidity and cause of death.MethodsPatients who had undergone surgery for PA‐VSD from January 1st 1994 to December 31st 2017 were studied retrospectively. Survival was cross‐checked against the Swedish National Population Register.ResultsSeventy patients were identified, giving an incidence of 5.3 newborns per 100 000 live births. In 41 patients (59%) the pulmonary blood flow originated from a patent ductus arteriosus (PDA), while 29 patients (41%) had contribution of the pulmonary blood flow from MAPCAs. Extracardiac disease was found in 34 patients (49%), 16 of whom had 22q11‐microdeletion syndrome (23%). Survival at follow‐up was similar in patients with and without MAPCAs (72.4% vs. 75.6%, n.s.), with a median follow‐up time of 14.3 years (3.2–41.8 years). No difference was found in mortality in patients with or without any syndrome or extracardiac disease.ConclusionLong‐term survival did not differ between those with and without MAPCAs and no difference in mortality was seen in patients with and without concomitant extracardiac disease or any kind of syndrome.

SEVERE RESISTANT HYPOMAGNESEMIA AS THE FIRST CLINICAL PRESENTATION OF 17Q12 MICRODELETION SYNDROME

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Hypomagnesemia occurs with decreased gastrointestinal absorption, transcellular shifts, and increased renal excretion. It is often associated with other electrolyte abnormalities including hypokalemia, hypocalcemia, and alkalosis. Hypomagnesemia is seen in patients with certain genetic syndromes and antifungals, chemotherapeutics, and diuretics use. We describe a patient who presented with symptomatic, severe, resistant hypomagnesemia and was found to have 17q12 microdeletion syndrome. CASE PRESENTATION: The patient is a 43 year-old man with essential hypertension, ureteropelvic junction obstruction (repaired in childhood), and chronic hydronephrosis who was noted to have hypomagnesemia on routine blood work 3 years prior to presentation. He was admitted for fatigue, palpitations, and multiple presyncopal episodes. Vital signs showed blood pressure of 168/79mmHg and pulse of 69. The patient had a marfanoid habitus and mild cognitive impairment. Initial blood work showed a magnesium of 1.1 mg/dL, bicarbonate of 33 mmol/L, potassium of 3.3 mmol/L, creatinine of 1.3 mg/dL, AST 68 U/L, ALT 54 U/L, alkaline phosphatase of 122 U/L, and HbA1c of 5.4%. Renal ultrasound showed mild right hydronephrosis and severe left hydronephrosis with obstruction at the ureteropelvic junction. A 24-hour urine magnesium was elevated (211mg/24hrs), consistent with urinary magnesium wasting. The patient was started on magnesium chloride supplements and amiloride. He completed a 48 hour Holter monitor, exercise stress test, and echocardiogram for syncopal episodes. This showed frequent premature ventricular contractions. Hepatology evaluation for persistently elevated alkaline phosphatase and liver enzymes was negative for biliary pathology. Causes of his magnesium wasting were considered including Bartter’s syndrome, Gitelman’s syndrome or other calcium sensing receptor mutations. He had genetic testing and found to have 17q12 microdeletion syndrome. DISCUSSION: 17q12 deletion syndrome is associated with maturity onset diabetes of the young, urinary tract abnormalities, and cognitive impairment. Hepatocyte nuclear factor 1 B (HNF1B) is a transcription gene within the 17q12 deletion that has toxic effects on the distal convoluted tubule where magnesium transport is regulated. It is thought the HNF1B defect worsens with age which is why patients typically present with hypomagnesemia in the 5th decade of life. Severe coronary calcification and pancreatic atrophy have been reported with this syndrome as well. CONCLUSIONS: Hypomagnesemia can present as a wide spectrum of atypical symptoms. When resistant hypomagnesemia persists without obvious underlying etiology, genetic causes must be considered. Reference #1: Li, H. J., Groden, C., Hoenig, M. P., Ray, E. C., Ferreira, C. R., Gahl, W., & Novacic, D. (2019). Case report: extreme coronary calcifications and hypomagnesemia in a patient with a 17q12 deletion involving HNF1B. BMC nephrology, 20(1), 1-6. Reference #2: Agus, Z. S. (1999). Hypomagnesemia. Journal of the American Society of Nephrology, 10(7), 1616-1622. DISCLOSURES: No relevant relationships by Karthik Gonuguntla, source=Web Response No relevant relationships by Nikola Perosevic, source=Web Response No relevant relationships by Sruti Velamakanni, source=Web Response Subinvestigator relationship with Davita Clinical Research Please note: $1001 - $5000 Added 05/31/2020 by Christine Vigneault, source=Web Response, value=Grant/Research Support

Clinical and genetic features of glomerulocystic kidney in childhood

The review provides historical information on the study of renal cystosis that occurs with glomerular cysts, discusses terminology issues and classification of diseases that occur with glomerulocystic kidney. The course features, diagnostic methods, treatment, and prognosis of renal glomerulocystosis in children, renal and extrarenal manifestations of two subtypes of hereditary glomerulocystic kidney disease: autosomal dominant glomerulocystic kidney disease associated with mutations of uromodulin (OMIM 609886) and familial hypoplastic glomerulocystic kidney disease associated with mutations of the HNF-1β (TCF2) gene (OMIM 137920). Diagnostic tetrad of familial hypoplastic glomerulocystic kidney disease, features of course and prognosis of HNF-1β-associated kidney disease with very early onset (VEO), MODY5 diabetes caused by HNF-1β mutation and 17q12 microdeletion syndrome in children were detected. According to the results of ultrasound examination (US), the fetus and newborn reveal hyperechogenicity of the kidney parenchyma, the volume of which is increased or corresponds to normal values. Renal cysts in glomerulocystic kidney are small, located in the cortical layer or subcapsularly, single or multiple, rarely diagnosed in the neonatal period. In young children, US shows a picture of increasing hyperechogenicity of the parenchyma with visualization of renal cysts in the cortical layer or subcapsularly, a decrease in the volume or asymmetry in the size of the kidneys. Urinary syndrome in glomerulocystic kidney in childhood is characterized by hematuria, microproteinuria, magniuria and uraturia in combination with hypostenuria and polyuria. Molecular genetic research reveals the mutation of genes responsible for the development of inherited diseases that occur with glomerulocystic kidney, and largely determines the prognosis and management tactics of the patient. A systematic approach is needed in the diagnosis and treatment of glomerulocystic kidney in children in order to slow the progression of chronic kidney disease and extrarenal manifestations, and to maintain continuity of observation of patients in pediatric and adult nephrological structures.