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The Journal of Pediatrics Jan 1987Neonatal herpes simplex virus (HSV) infection is usually acquired at birth, although a few infants have had findings suggestive of intrauterine infection. We describe 13...
Neonatal herpes simplex virus (HSV) infection is usually acquired at birth, although a few infants have had findings suggestive of intrauterine infection. We describe 13 babies who had clinical manifestations of intrauterine HSV infection, including skin lesions and scars at birth (12), chorioretinitis (eight), microcephaly (seven), hydranencephaly (five), and microphthalmia (two). All infants had combinations of these defects. Infection was proved by viral isolation in each case; all isolates were HSV-2. Two infants died during the first week of life; 10 of the surviving infants had severe neurologic sequelae, and one infant was blind. Four mothers experienced an apparent primary genital HSV infection, and one had recurrent infection, at varying times during gestation. The remaining women denied a history of symptoms of genital HSV infection. These findings indicate that intrauterine HSV infection can occur as a consequence of either primary or recurrent maternal infection and has severe consequences for the fetus.
Topics: Abnormalities, Multiple; Adolescent; Adult; Central Nervous System; Chorioretinitis; Double-Blind Method; Female; Fetal Diseases; Herpes Simplex; Humans; Infant, Newborn; Male; Microphthalmos; Pregnancy; Pregnancy Complications, Infectious; Prognosis; Recurrence; Skin Abnormalities
PubMed: 3794894
DOI: 10.1016/s0022-3476(87)80298-6 -
Frontiers in Genetics 2023Research on fetal loss related to germline mutations in single genes remains limited. Disruption of has recently been established in association with perinatal deaths...
Research on fetal loss related to germline mutations in single genes remains limited. Disruption of has recently been established in association with perinatal deaths characterized by hydranencephaly, renal dysplasia, oligohydramnios, and characteristic dysmorphisms. We herein present a Chinese family with recurrent fetal losses due to compound heterozygous nonsense variants. The Chinese couple had a history of five pregnancies, with four of them proceeding abnormally. Two stillbirths (II:3 and II:4) sequentially occurred in the third and fourth pregnancy. Prenatal ultrasound scans revealed phenotypic similarities between fetuses II:3 and II:4, including oligohydramnios, bilateral renal dysplasia and hydrocephalus/hydranencephaly. Clubfoot and syndactyly were also present in both stillborn babies. Fetus II:3 presented with endocardial cushion defects while fetus II:4 did not. With the product of conception in the fourth pregnancy, whole exome sequencing (WES) on fetus II:4 identified compound heterozygous nonsense variants comprised of c.190C>T(p.Arg64*) and c.208A>T(p.Lys70*). Both variants were expected to result in lack of the TSG101 and ALIX binding domain. Sanger sequencing confirmed the presence and cosegregation of both variants. This is the fifth reported family wherein biallelic variants lead to multiple perinatal deaths. Our findings, taken together with previously described phenotypically similar cases and even those with a milder and viable phenotype, broaden the genotypic and phenotypic spectrum of -associated lethal fetal syndrome, highlighting the vital biomolecular function of CEP55.
PubMed: 37928238
DOI: 10.3389/fgene.2023.1267241 -
British Medical Journal Jun 1974
Topics: Brain Diseases; Cysts; Humans; Hydranencephaly; Methods; Skull; Subdural Effusion; Transillumination
PubMed: 4835455
DOI: 10.1136/bmj.2.5920.671-c -
Molecular Genetics & Genomic Medicine May 2018Fowler syndrome is a rare autosomal recessive disorder characterized by hydranencephaly-hydrocephaly and multiple pterygium due to fetal akinesia. To date, around 45...
BACKGROUND
Fowler syndrome is a rare autosomal recessive disorder characterized by hydranencephaly-hydrocephaly and multiple pterygium due to fetal akinesia. To date, around 45 cases from 27 families have been reported, and the pathogenic bi-allelic mutations in FLVCR2 gene described in 15 families. The pathogenesis of this condition has not been fully elucidated so far.
METHODS
We report on an additional family with two affected fetuses carrying a novel homozygous mutation in FLVCR2 gene, and describe the impact of known mutants on the protein structural and functional impairment.
RESULTS
The present report confirms the genetic homogeneity of Fowler syndrome and describes a new FLVCR2 mutation affecting the protein function. The structural analysis of the present and previously published FLVCR2 mutations supports the hypothesis of a reduced heme import as the underlying disease's mechanism due to the stabilization of the occluded conformation or a protein misfolding.
CONCLUSION
Our data suggest the hypothesis of heme deficiency as the major pathogenic mechanism of Fowler syndrome.
Topics: Alleles; Amino Acid Sequence; Fetus; Heme; Humans; Hydranencephaly; Hydrocephalus; Membrane Transport Proteins; Mutation; Receptors, Virus; Vascular Diseases
PubMed: 29500860
DOI: 10.1002/mgg3.376 -
European Journal of Human Genetics :... Apr 2019The centrosomal protein 55 kDa (CEP55 (OMIM 610000)) plays a fundamental role in cell cycle regulation and cytokinesis. However, the precise role of CEP55 in human...
The centrosomal protein 55 kDa (CEP55 (OMIM 610000)) plays a fundamental role in cell cycle regulation and cytokinesis. However, the precise role of CEP55 in human embryonic growth and development is yet to be fully defined. Here we identified a novel homozygous founder frameshift variant in CEP55, present at low frequency in the Amish community, in two siblings presenting with a lethal foetal disorder. The features of the condition are reminiscent of a Meckel-like syndrome comprising of Potter sequence, hydranencephaly, and cystic dysplastic kidneys. These findings, considered alongside two recent studies of single families reporting loss of function candidate variants in CEP55, confirm disruption of CEP55 function as a cause of this clinical spectrum and enable us to delineate the cardinal clinical features of this disorder, providing important new insights into early human development.
Topics: Amish; Cell Cycle Proteins; Centrosome; Consanguinity; Cytokinesis; Female; Frameshift Mutation; Homozygote; Humans; Hydranencephaly; Infant, Newborn; Kidney; Kidney Diseases; Male; Phosphorylation; Twins
PubMed: 30622327
DOI: 10.1038/s41431-018-0306-0 -
Veterinary World Sep 2017The study was conducted in Basrah, Iraq, to diagnose congenital arthrogryposis-hydranencephaly syndrome caused by Akabane virus (AKAV) in calves.
AIM
The study was conducted in Basrah, Iraq, to diagnose congenital arthrogryposis-hydranencephaly syndrome caused by Akabane virus (AKAV) in calves.
MATERIALS AND METHODS
Affected animals (42 calves) are about 2-27 days old from both sexes show signs of arthrogryposis and hydranencephaly. Eight clinically healthy newborn calves were considered as controls. Diagnosis of AKAV was confirmed using a competition enzyme-linked immunosorbent assay test.
RESULTS
Results show that all affected calves were found seropositive. Furthermore, a significant increase in total leukocyte count in diseased calves due to a significant increase in the absolute lymphocyte number indicated in affected calves than in controls. Moreover, a significant increase in sedimentation rate of erythrocytes was also encountered in diseased calves than in controls. In addition, a significant increase in haptoglobin level and fibrinogen was also detected.
CONCLUSION
Diagnosis of AKAV infection of Basrah Governorate, Iraq, will provide useful epidemiological information for cattle and other domesticated animals. Therefore, abortion could be prevented and controlled.
PubMed: 29062207
DOI: 10.14202/vetworld.2017.1143-1148 -
Neurology India 2020
Topics: Adult; Cesarean Section; Female; HIV Seropositivity; Humans; Hydranencephaly; Infant, Newborn; Pregnancy; Tomography, X-Ray Computed
PubMed: 32129279
DOI: 10.4103/0028-3886.279698 -
Journal of Medical Genetics Jul 2017Hydranencephaly is a congenital anomaly leading to replacement of the cerebral hemispheres with a fluid-filled cyst. The goals of this work are to describe a novel...
BACKGROUND
Hydranencephaly is a congenital anomaly leading to replacement of the cerebral hemispheres with a fluid-filled cyst. The goals of this work are to describe a novel autosomal-recessive syndrome that includes hydranencephaly (multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly (MARCH)); to identify its genetic cause(s) and to provide functional insight into pathomechanism.
METHODS
We used homozygosity mapping and exome sequencing to identify recessive mutations in a single family with three affected fetuses. Immunohistochemistry, RT-PCR and imaging in cell lines, and zebrafish models, were used to explore the function of the gene and the effect of the mutation.
RESULTS
We identified a homozygous nonsense mutation in segregating with MARCH. Testing the effect of this allele on patient-derived cells indicated both a reduction of the overall message and the production of a message that likely gives rise to a truncated protein. Suppression or ablation of in zebrafish embryos recapitulated key features of MARCH, most notably renal dysplasia, cerebellar hypoplasia and craniofacial abnormalities. These phenotypes could be rescued by full-length but not truncated human message. Finally, we expressed the truncated form of CEP55 in human cells, where we observed a failure of truncated protein to localise to the midbody, leading to abscission failure and multinucleated daughter cells.
CONCLUSIONS
loss of function mutations likely underlie MARCH, a novel multiple congenital anomaly syndrome. This association expands the involvement of centrosomal proteins in human genetic disorders by highlighting a role in midbody function.
Topics: Abnormalities, Multiple; Animals; Base Sequence; CRISPR-Cas Systems; Cell Cycle Proteins; Female; Fibroblasts; Gene Editing; Humans; Infant; Male; Mitosis; Models, Biological; Mutation; Neurons; Nuclear Proteins; Pedigree; Phenotype; Subcellular Fractions; Syndrome; Zebrafish; Zebrafish Proteins
PubMed: 28264986
DOI: 10.1136/jmedgenet-2016-104296 -
Choroid Plexectomy for Hydrocephalus Management in a Pediatric Patient with a Pilocytic Astrocytoma.Journal of Neurosciences in Rural... Oct 2021Choroid plexectomy is a debated surgical intervention for the treatment of hydranencephaly and chronic infected hydrocephalus. We present a case of a 2-year-old with...
Choroid plexectomy is a debated surgical intervention for the treatment of hydranencephaly and chronic infected hydrocephalus. We present a case of a 2-year-old with multiple shunt revisions and hydrocephalus secondary to a pilocytic astrocytoma. He presented with new somnolence, vomiting, and abdominal distension 5 months post subtotal tumor resection, with a history of shunt revisions and infections related to his chemotherapy-induced low white blood cell count. He underwent choroid plexus coagulation and resection. Three years post choroid plexectomy, the patient continues to meet neurodevelopmental milestones and is shunt independent. While ventricular shunt placement is the most common course of treatment, choroid plexectomy should be considered as an alternative treatment of hydrocephalus secondary to other neurological disorders, especially when the patient is immunocompromised, to avoid the recurrent infections seen with shunt placement.
PubMed: 34737521
DOI: 10.1055/s-0041-1735244 -
AJP Reports Jan 2021A 32-year-old female with a history of three prior pregnancy losses presented for genetic testing following an ultrasonography diagnosis of fetal hydranencephaly....
A 32-year-old female with a history of three prior pregnancy losses presented for genetic testing following an ultrasonography diagnosis of fetal hydranencephaly. Baby was born via C-section and was noted to have a head circumference of 48 cm, in addition to ocular and cardiac anomalies and dysmorphic features. Whole genome sequencing revealed a homozygous variant in gene. The pathobiogenesis of hydranencephaly is incompletely understood and is attributed to vascular, infectious, or genetic etiology. Herein we present as a monogenic cause of fetal hydranencephaly which was incompatible with life. Previously, -associated phenotype consisted of cobblestone lissencephaly and hydrocephalus, developmental delay, and seizures. Our proband expands the phenotypic spectrum of this malformative encephalopathy.
PubMed: 33542858
DOI: 10.1055/s-0040-1722728