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Endocrinology, Diabetes & Metabolism... 2017In the absence of maternal thyroid disease or iodine deficiency, fetal goitre is rare and usually attributable to dyshormonogenesis, for which genetic ascertainment is...
Intrauterine death following intraamniotic triiodothyronine and thyroxine therapy for fetal goitrous hypothyroidism associated with polyhydramnios and caused by a thyroglobulin mutation.
UNLABELLED
In the absence of maternal thyroid disease or iodine deficiency, fetal goitre is rare and usually attributable to dyshormonogenesis, for which genetic ascertainment is not always undertaken in the UK. Mechanical complications include tracheal and oesophageal compression with resultant polyhydramnios, malpresentation at delivery and neonatal respiratory distress. We report an Indian kindred in which the proband (first-born son) had congenital hypothyroidism (CH) without obvious neonatal goitre. His mother's second pregnancy was complicated by fetal hypothyroid goitre and polyhydramnios, prompting amniotic fluid drainage and intraamniotic therapy (with liothyronine, T3 and levothyroxine, T4). Sadly, intrauterine death occurred at 31 weeks. Genetic studies in the proband demonstrated compound heterozygous novel (c.5178delT, p.A1727Hfs*26) and previously described (c.7123G > A, p.G2375R) thyroglobulin () mutations which are the likely cause of fetal goitre in the deceased sibling. mutations rarely cause fetal goitre, and management remains controversial due to the potential complications of intrauterine therapy however an amelioration in goitre size may be achieved with intraamniotic T4, and intraamniotic T3/T4 combination has achieved a favourable outcome in one case. A conservative approach, with surveillance, elective delivery and commencement of levothyroxine neonatally may also be justified, although intubation may be required post delivery for respiratory obstruction. Our observations highlight the lethality which may be associated with fetal goitre. Additionally, although this complication may recur in successive pregnancies, our case highlights the possibility of discordance for fetal goitre in siblings harbouring the same dyshormonogenesis-associated genetic mutations. Genetic ascertainment may facilitate prenatal diagnosis and assist management in familial cases.
LEARNING POINTS
CH due to biallelic, loss-of-function mutations is well-described and readily treatable in childhood however mechanical complications from associated fetal goitre may include polyhydramnios, neonatal respiratory compromise and neck hyperextension with dystocia complicating delivery.CH due to mutations may manifest with variable phenotypes, even within the same kindred.Treatment options for hypothyroid dyshormogenic fetal goitre in a euthyroid mother include intraamniotic thyroid hormone replacement in cases with polyhydramnios or significant tracheal obstruction. Alternatively, cases may be managed conservatively with radiological surveillance, elective delivery and neonatal levothyroxine treatment, although intubation and ventilation may be required to support neonatal respiratory compromise.Genetic ascertainment in such kindreds may enable prenatal diagnosis and anticipatory planning for antenatal management of further affected offspring.
PubMed: 28620499
DOI: 10.1530/EDM-17-0040 -
Diagnostics (Basel, Switzerland) May 2022Polyhydramnios is an obstetrical condition defined as a pathological increase in the amniotic fluid and is associated with a high risk of maternal-fetal complications....
Polyhydramnios is an obstetrical condition defined as a pathological increase in the amniotic fluid and is associated with a high risk of maternal-fetal complications. Common causes of polyhydramnios include fetal anatomical and genetic abnormalities, gestational diabetes mellitus, and fetal viral infections. We present the case of a 30-year-old Caucasian woman with transient polyhydramnios associated with gestational diabetes mellitus and obstetric complications. The diagnosis was based on the ultrasound assessment of amniotic fluid volume during a common examination at 26 weeks. Two weeks prior, the patient had been diagnosed with gestational diabetes mellitus. After 4 days, the patient was examined, and the amniotic fluid index returned to normal values. At 38 weeks, the patient presented to the emergency room due to lack of fetal active movement. Ultrasound revealed polyhydramnios, the patient was admitted for severe fetal bradycardia, and fetal extraction through emergency cesarian section was performed. Six weeks after birth, the patient underwent an oral glucose tolerance test with normal values, confirming gestational diabetes mellitus. We performed a systematic review of the literature on polyhydramnios, from January 2016 to April 2022, to analyze all recent published cases and identify the most common etiological causes and important aspects related to maternal-fetal outcomes.
PubMed: 35741150
DOI: 10.3390/diagnostics12061340 -
Orphanet Journal of Rare Diseases Jul 2022Alterations in the MYH7 gene can cause cardiac and skeletal myopathies. MYH7-related skeletal myopathies are extremely rare, and the vast majority of causal variants in... (Review)
Review
A recurrent single-amino acid deletion (p.Glu500del) in the head domain of ß-cardiac myosin in two unrelated boys presenting with polyhydramnios, congenital axial stiffness and skeletal myopathy.
BACKGROUND
Alterations in the MYH7 gene can cause cardiac and skeletal myopathies. MYH7-related skeletal myopathies are extremely rare, and the vast majority of causal variants in the MYH7 gene are predicted to alter the rod domain of the of ß-cardiac myosin molecule, resulting in distal muscle weakness as the predominant manifestation. Here we describe two unrelated patients harboring an in-frame deletion in the MYH7 gene that is predicted to result in deletion of a single amino acid (p.Glu500del) in the head domain of ß-cardiac myosin. Both patients display an unusual skeletal myopathy phenotype with congenital axial stiffness and muscular hypertonus, but no cardiac involvement.
RESULTS
Clinical data, MRI results and histopathological data were collected retrospectively in two unrelated boys (9 and 3.5 years old). Exome sequencing uncovered the same 3-bp in-frame deletion in exon 15 (c.1498_1500delGAG) of the MYH7 gene of both patients, a mutation which deletes a highly conserved glutamate residue (p.Glu500del) in the relay loop of the head domain of the ß-cardiac myosin heavy chain. The mutation occurred de novo in one patient, whereas mosaicism was detected in blood of the father of the second patient. Both boys presented with an unusual phenotype of prenatal polyhydramnios, congenital axial stiffness and muscular hypertonus. In one patient the phenotype evolved into an axial/proximal skeletal myopathy without distal involvement or cardiomyopathy, whereas the other patient exhibited predominantly stiffness and respiratory involvement. We review and compare all patients described in the literature who possess a variant predicted to alter the p.Glu500 residue in the ß-cardiac myosin head domain, and we provide in-silico analyses of potential effects on polypeptide function.
CONCLUSION
The data presented here expand the phenotypic spectrum of mutations in the MYH7 gene and have implications for future diagnostics and therapeutic approaches.
Topics: Amino Acids; Cardiac Myosins; Female; Humans; Muscle, Skeletal; Muscular Diseases; Mutation; Myosin Heavy Chains; Polyhydramnios; Retrospective Studies
PubMed: 35854315
DOI: 10.1186/s13023-022-02421-7 -
Annales de Biologie Clinique Apr 2017Bartter syndrome is a severe inherited tubulopathy characterized at birth by salt wasting, severe polyuria, dehydration, growth retardation and secondary...
Bartter syndrome is a severe inherited tubulopathy characterized at birth by salt wasting, severe polyuria, dehydration, growth retardation and secondary hyperaldosteronism. Prenatally, the disease is usually discovered following onset of severe polyhydramnios. We studied amniotic fluid aldosterone concentration in cases of Bartter syndrome and in control groups. Amniotic fluid aldosterone was assayed by radioimmunoassay. We undertook a retrospective case-control study based on 36 cases of postnatally diagnosed Bartter syndrome and 144 controls matched for gestational age. Two controls groups were defined: controls with polyhydramnios (n=72) and control without polyhydramnios (n=72). Amniotic fluid aldosterone was compared between the three groups. The median amniotic fluid aldosterone concentration in the Bartter syndrome group (90 pg/mL) did not differ significantly from that in the controls with polyhydramnios (90 pg/mL, p=0.33) or the controls without polyhydramnios (87 pg/mL, p=0.41). In conclusion, amniotic fluid aldosterone assay cannot be used for prenatal diagnosis of Bartter syndrome.
Topics: Aldosterone; Amniotic Fluid; Bartter Syndrome; Case-Control Studies; Female; Gestational Age; Humans; Hyperaldosteronism; Polyhydramnios; Pregnancy; Prenatal Diagnosis; Radioimmunoassay; Retrospective Studies
PubMed: 28377333
DOI: 10.1684/abc.2017.1229 -
The New England Journal of Medicine May 2016Three pregnancies with male offspring in one family were complicated by severe polyhydramnios and prematurity. One fetus died; the other two had transient massive...
BACKGROUND
Three pregnancies with male offspring in one family were complicated by severe polyhydramnios and prematurity. One fetus died; the other two had transient massive salt-wasting and polyuria reminiscent of antenatal Bartter's syndrome.
METHODS
To uncover the molecular cause of this possibly X-linked disease, we performed whole-exome sequencing of DNA from two members of the index family and targeted gene analysis of other members of this family and of six additional families with affected male fetuses. We also evaluated a series of women with idiopathic polyhydramnios who were pregnant with male fetuses. We performed immunohistochemical analysis, knockdown and overexpression experiments, and protein-protein interaction studies.
RESULTS
We identified a mutation in MAGED2 in each of the 13 infants in our analysis who had transient antenatal Bartter's syndrome. MAGED2 encodes melanoma-associated antigen D2 (MAGE-D2) and maps to the X chromosome. We also identified two different MAGED2 mutations in two families with idiopathic polyhydramnios. Four patients died perinatally, and 11 survived. The initial presentation was more severe than in known types of antenatal Bartter's syndrome, as reflected by an earlier onset of polyhydramnios and labor. All symptoms disappeared spontaneously during follow-up in the infants who survived. We showed that MAGE-D2 affects the expression and function of the sodium chloride cotransporters NKCC2 and NCC (key components of salt reabsorption in the distal renal tubule), possibly through adenylate cyclase and cyclic AMP signaling and a cytoplasmic heat-shock protein.
CONCLUSIONS
We found that MAGED2 mutations caused X-linked polyhydramnios with prematurity and a severe but transient form of antenatal Bartter's syndrome. MAGE-D2 is essential for fetal renal salt reabsorption, amniotic fluid homeostasis, and the maintenance of pregnancy. (Funded by the University of Groningen and others.).
Topics: Adaptor Proteins, Signal Transducing; Antigens, Neoplasm; Bartter Syndrome; Female; Fetal Death; Fetal Diseases; Fetus; Genetic Diseases, X-Linked; Humans; Kidney; Male; Mutation; Pedigree; Polyhydramnios; Pregnancy; Premature Birth; Sequence Analysis, DNA; Sodium Chloride Symporters; Solute Carrier Family 12, Member 1
PubMed: 27120771
DOI: 10.1056/NEJMoa1507629 -
The Journal of Maternal-fetal &... Dec 2023Congenital pulmonary airway malformations (CPAMs) are rare sporadic lesions frequently associated with poor fetal prognosis. Type 3 CPAMs are characterized by small... (Review)
Review
INTRODUCTION
Congenital pulmonary airway malformations (CPAMs) are rare sporadic lesions frequently associated with poor fetal prognosis. Type 3 CPAMs are characterized by small hyperechogenic cysts (<5 mm). Hydrops often develops secondarily, and the fetal survival rate is approximately 5% in this setting.
CASE PRESENTATION
We present a case of a large type 3 CPAM complicated by fetal hydrops. The lesion was detected at 19 gestational weeks (GW) and confirmed by fetal MRI at 29 GW. At 22 GW, a course of maternal steroids was given as a possible treatment of type 3 CPAM. Peritoneal-amniotic shunt was placed twice to reduce fetal ascites, with unsatisfactory results. Similarly, polyhydramnios was relieved by two amnioreductions, but redeveloped soon after. A baby girl was delivered spontaneously at 33 GW and received a two-stage partial lobectomy in the first three months of life. Desaturations necessitated challenging invasive oscillatory ventilation between stages. Her outcome is unexpectedly positive and she may expect a good quality of life. She now approaches one year of age, with near-to-normal growth and developmental milestones.
DISCUSSION
Type 3 CPAMs complicated by fetal hydrops are associated with high perinatal mortality. While open fetal surgery remains a viable option in select specialist centers, antenatal interventions are typically ineffective. The survival of this infant can be attributed to prenatal management and early postnatal surgical intervention. The lack of guidelines for ventilation in this setting was a significant challenge for neonatal intensivists. Multidisciplinary vigilance and collaboration with frequent specialist follow ups were the key to success for both mother and child.
Topics: Humans; Infant; Infant, Newborn; Child; Pregnancy; Female; Hydrops Fetalis; Quality of Life; Cystic Adenomatoid Malformation of Lung, Congenital; Lung; Prenatal Care; Ultrasonography, Prenatal
PubMed: 37581300
DOI: 10.1080/14767058.2023.2239424 -
The Israel Medical Association Journal... Feb 2011
Topics: Amniocentesis; Female; Fetal Diseases; Humans; Hyperostosis, Cortical, Congenital; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Polyhydramnios; Pregnancy; Radiography; Ultrasonography, Prenatal
PubMed: 21443040
DOI: No ID Found -
Acta Medica (Hradec Kralove) 2022The aim of our manuscript is to report of a successful perinatal outcome after treatment of acute polyhydramnios caused by duodenal atresia. A 34-year-old G3P1 was...
The aim of our manuscript is to report of a successful perinatal outcome after treatment of acute polyhydramnios caused by duodenal atresia. A 34-year-old G3P1 was referred due to polyhydramnios in the 30th week of pregnancy. Ultrasound revealed polyhydramnios, amniotic fluid index (AFI) 28, and a double bubble sign that indicated duodenal atresia and dilatated oesophagus. In the 32nd week of gestation, the volume of amniotic fluid increases, AFI 35, along with symptoms of dyspnea and abdominal pain. Due to the clinical picture and the early gestational age, it was decided to perform an amnioreduction. In the 36th week of gestation cesarean section was performed. The baby was taken for exploratory laparotomy and found to have a simultaneous complete duodenal atresia and annular pancreas with associated dilated the first portion of the duodenum and the stomach. A side-to-side duodenoduodenostomy via single-layer hand-sewn anastomosis was performed over a transanastamotic feeding tube (TAFT). The postoperative course was uneventful. Amnioreduction is useful and safe in the treatment of acute polyhydramnios caused by duodenal atresia and thus has a significant role in prolonging gestation until fetal maturity.
Topics: Pregnancy; Humans; Female; Adult; Polyhydramnios; Pregnancy Outcome; Cesarean Section; Amniotic Fluid
PubMed: 36942706
DOI: 10.14712/18059694.2023.6 -
Ultrasound in Obstetrics & Gynecology :... May 2015The accuracy of prenatal ultrasound examination in detecting jejunal and ileal atresia has been reported in the literature to be highly variable, at 25-90%. The aim of... (Review)
Review
OBJECTIVE
The accuracy of prenatal ultrasound examination in detecting jejunal and ileal atresia has been reported in the literature to be highly variable, at 25-90%. The aim of this systematic review was to evaluate the accuracy of prenatal ultrasound in detecting non-duodenal small bowel atresia (ND-SBA).
METHODS
MEDLINE, EMBASE and The Cochrane Library, including The Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE) and The Cochrane Central Register of Controlled Trials (CENTRAL), were searched electronically. The overall detection rate of jejunal or ileal atresia using ultrasound was reported. The accuracy of using polyhydramnios and dilated loops of bowel as diagnostic signs was also explored.
RESULTS
Sixteen studies involving 640 fetuses were included in this review. The detection rate of ND-SBA by prenatal ultrasound was highly variable, with values ranging from 10 to 100%, with an overall prediction of 50.6% (95% CI, 38.0-63.2%). When analyzed separately, the detection rates of jejunal and ileal atresia were 66.3%, (95% CI, 33.9-91.8%) and 25.9% (95% CI, 4.0-58.0%), respectively. Both dilated loops of bowel and polyhydramnios as diagnostic signs for ND-SBA provided a low overall detection rate.
CONCLUSIONS
The diagnostic performance of prenatal ultrasound in identifying ND-SBA is extremely variable. Large studies are needed in order to identify objective and combined criteria for the diagnosis of these anomalies.
Topics: Female; Humans; Ileum; Infant, Newborn; Intestinal Atresia; Intestine, Small; Jejunum; Pregnancy; Reproducibility of Results; Sensitivity and Specificity; Ultrasonography, Prenatal
PubMed: 25157626
DOI: 10.1002/uog.14651 -
Molecular Cytogenetics 2019Pallister-Killian syndrome (PKS) (OMIM:#601803) is a rare sporadic genetic disorder characterized by multi-malformations which is caused by the presence of the extra...
BACKGROUND
Pallister-Killian syndrome (PKS) (OMIM:#601803) is a rare sporadic genetic disorder characterized by multi-malformations which is caused by the presence of the extra isochromosome 12p. PKS is featured by the tissue-limited mosaicism of the isochromosome 12p [i(12p)]. There were a wide spectrum of prenatal ultrasound findings of PKS, which made it difficult to be found in first or second trimester. Polyhydramnios, diaphragmatic hernia, and rhizomelic limb shortening were the most common prenatal ultrasound abnormalities in PKS. This study retrospectively analyzed the ultrasound findings and molecular cytogenetic results of four PKS fetuses diagnosed by using cord blood samples.
RESULTS
The ultrasound anomalies of four PKS fetuses are described as follows: fetal macrosomia, cerebral ventriculomegaly, increased NT thickness, rhizomelic limbs shortening, polyhydramnios. Biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), femur length (FL) measurements were above the mean in three fetuses,while one fetus showed rhizomelic limbs shortening. Combined with this study and previous literature, polyhydramnios was the most frequent anomaly observed in prenatal ultrasound examination of PKS, which accounted for 48% (94/194). Fetal macrosomia was present in 15% (29/194), cerebral ventriculomegaly in 13% (25/194), thickened nuchal fold in 9% (18/194), rhizomelic limbs shortening in 26% (51/194). I(12p) was found in the karyotype analysis of cultured cord blood lymphocytes and the mosaic ratios ranged from 2 to 5%. Single nucleotide polymorphisms array (SNP-array) results suggested that the whole short arm of chromosome 12 was duplicated with 2~3 copies. Fluorescence in situ hybridization (FISH) was performed to confirm the results of karyotype and SNP-array.
CONCLUSIONS
In case non-specific indicators such as fetal macrosomia, polyhydramnios and rhizomelic limbs shortening are observed meanwhile in prenatal ultrasound, targeted detection of PKS should be considered. In the prenatal diagnosis of PKS, the combination of SNP-array and FISH with conventional karyotype are the key to seek i(12p) and for precise diagnosis.
PubMed: 31497069
DOI: 10.1186/s13039-019-0449-x