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Archives of Gynecology and Obstetrics Dec 2023To explore pathogenic/likely pathogenic copy number variations (P/LP CNVs) and regions of homozygosity (ROHs) in fetal central nervous system (CNS) malformations.
OBJECTIVE
To explore pathogenic/likely pathogenic copy number variations (P/LP CNVs) and regions of homozygosity (ROHs) in fetal central nervous system (CNS) malformations.
METHODS
A cohort of 539 fetuses with CNS malformations diagnosed by ultrasound/MRI was retrospectively analyzed between January 2016 and December 2019. All fetuses were analyzed by chromosomal microarray analysis (CMA). Three cases with ROHs detected by CMA were subjected to whole-exome sequencing (WES). The fetuses were divided into two groups according to whether they had other structural abnormalities. The CNS phenotypes of the two groups were further classified as simple (one type) or complicated (≥ 2 types).
RESULTS
(1) A total of 35 cases with P/LP CNVs were found. The incidence of P/LP CNVs was higher in the extra-CNS group [18.00% (9/50)] than in the isolated group [5.32% (26/489)] (P < 0.01), while there was no significant difference between the simpletype and complicated-type groups. (2) In the simple-type group, the three most common P/LP CNV phenotypes were holoprosencephaly, Dandy-Walker syndrome, and exencephaly. There were no P/LP CNVs associated with anencephaly, microcephaly, arachnoid cysts, ependymal cysts, or intracranial hemorrhage. (3) Only four cases with ROHs were found, and there were no cases of uniparental disomy or autosomal diseases.
CONCLUSION
The P/LP CNV detection rates varied significantly among the different phenotypes of CNS malformations, although simple CNS abnormalities may also be associated with genetic abnormalities.
Topics: Pregnancy; Female; Humans; DNA Copy Number Variations; Retrospective Studies; Fetus; Nervous System Malformations; Microarray Analysis; Central Nervous System Diseases; Prenatal Diagnosis; Chromosome Aberrations
PubMed: 36464758
DOI: 10.1007/s00404-022-06866-w -
Pediatric Dermatology Jan 2023Keratitis-ichthyosis-deafness syndrome is a rare genetic disease presenting with cutaneous, ocular, and otic defects. This comprehensive review provides insight into the... (Review)
Review
Keratitis-ichthyosis-deafness syndrome is a rare genetic disease presenting with cutaneous, ocular, and otic defects. This comprehensive review provides insight into the clinical presentations, highlighting the cutaneous manifestations including histopathology and treatment options.
Topics: Humans; Deafness; Ichthyosis; Syndrome; Skin
PubMed: 36444857
DOI: 10.1111/pde.15201 -
Taiwanese Journal of Obstetrics &... Nov 2022We present a female neonate with de novo trisomy 9p24.3-q21.2 presented with a neurological anomaly.
OBJECTIVE
We present a female neonate with de novo trisomy 9p24.3-q21.2 presented with a neurological anomaly.
CASE REPORT
Her birth length was 41 cm (<3rd percentile), birth body weight was 1600 g (<5th percentile), and head circumference was 29.5 cm (<5th percentile). She had low-set ears, deep and wide-set eyes with downslanting palpebral fissures, and a full nasal bridge with a globular nose. In addition, a rocker bottom foot was noted after further evaluation. Congenital heart anomalies, including patent ductus arteriosus (0.43 cm), large atrial septal defect, and malalignment ventricular septal defect (0.64 cm) were also confirmed. Brain magnetic resonance imaging showed partial agenesis of the cerebellum and corpus callosum. Furthermore, severe bilateral communicating hydrocephalus was found. CTG-banded chromosome analysis revealed 47, XX, +mar.
CONCLUSION
DNA analysis may be mandatory for small gene segments. In trisomy 9p, we proposed further delineation of the critical region correlating to neurological malformations.
Topics: Humans; Infant, Newborn; Female; Dandy-Walker Syndrome; Trisomy; Abnormalities, Multiple; Hydrocephalus
PubMed: 36427979
DOI: 10.1016/j.tjog.2022.05.018 -
Medicine Nov 2022Dandy-Walker syndrome (DWS) is a group of brain malformations which occasionally accompanied by psychotic symptoms. The co-occurrence of DWS and epilepsy in children is... (Review)
Review
BACKGROUNDS
Dandy-Walker syndrome (DWS) is a group of brain malformations which occasionally accompanied by psychotic symptoms. The co-occurrence of DWS and epilepsy in children is quite rare.
CASE DESCRIPTION
We reported a 14-year-old male who presented with a 8-month history of inconsistent upper limb tremor and accidental seizure. The MRI showed the typical alterations of DWS: cystic dilatation of the fourth ventricle, vermian hypoplasia, enlarged posterior fossa. He received the ventriculoperitoneal shunting (VPS) placement for hydrocephalus and had a symptom-free period for 8 days. Then he experienced a recurrence of involuntary upper limb tremor and behavior disturbance after decreasing the pressure of cerebrospinal fluid (CSF) from 150 to 130 mm Hg. After being treated with Olanzapine 10 mg/d, Clonazepam 3 mg/qn and Valproate acid (VPA) 500 mg/bid for nearly a month, his mental status and psychotic symptoms fluctuated. A search of Pub Med showed little report of hydrocephalus and DWS comorbidity with seizure and psychosis. Here we presented the whole process of a rare disease from the very beginning with all his symptoms, examinations and treatments.
CONCLUSION
VPS placement surgery at an earlier stage may be an effective way to avoid inevitable brain damage so as to improve the clinical outcomes for patients with DWS. Continued treatment with regard to DWS condition may include shunt placement, but it mainly focus on developmental concerns, with occupational and physical therapy along with ongoing supportive psychotherapy to improve the coping skills and quality of life.
Topics: Humans; Male; Child; Adolescent; Dandy-Walker Syndrome; Quality of Life; Tremor; Hydrocephalus; Seizures
PubMed: 36401431
DOI: 10.1097/MD.0000000000031421 -
Frontiers in Genetics 2022Tetrasomy 9p is a rare syndrome characterized by fetal growth restriction, Dandy-Walker malformation, cardiac anomalies, and facial abnormalities and is discovered by...
Tetrasomy 9p is a rare syndrome characterized by fetal growth restriction, Dandy-Walker malformation, cardiac anomalies, and facial abnormalities and is discovered by ultrasound during the prenatal examination. Herein, we report a fetus of tetrasomy 9p without obvious phenotypic manifestations during the first trimester that was identified by non-invasive prenatal testing (NIPT). NIPT revealed that the gain of 9p24.3-9p11 that was approximately 46.36 Mb in size. Karyotyping of amniocytes indicated an additional marker in all metaphase. Chromosome microarray and fluorescence hybridization on uncultured amniocytes revealed tetrasomic of 9p24.3q13, and that the supernumerary chromosome is a dicentric isochromosome consisted of two copies of the 9p arm. Taken together, it was indicated that the fetal karyotype was 47,XY,+idic (9) (q13), and that multiple techniques are crucial to the prenatal diagnosis.
PubMed: 36386834
DOI: 10.3389/fgene.2022.1020525 -
Journal of Paediatrics and Child Health Jan 2023To find out the relative incidence and outcome of posterior fossa abnormality (PFA) in terms of survival at birth until 2 years of age.
AIM
To find out the relative incidence and outcome of posterior fossa abnormality (PFA) in terms of survival at birth until 2 years of age.
METHODS
We conducted a prospective study; all fetuses diagnosed with posterior fossa abnormality were followed-up. The outcome was observed with respect to survival, the presence of associated anomalies, the existence of developmental delay after a telephonic interview.
RESULTS
Out of 2703 children with congenital anomalies, 921 (34.1%) had a central nervous system defect; 76 cases of PFA were fully followed. Dandy-Walker malformation (DWM) was present in 50% (38/76), mega cisterna magna 18.4% (14/76), Blake pouch cyst 13.2% (10/76), vermian hypoplasia (VH) 13.2% (10/76) and arachnoid cyst 5.2% (4/76). The diagnosis was possible before 20 weeks in only 12 (15.8%) cases. The mean gestational age at delivery was 34.7 ± 6.7 weeks. Associated anomalies were seen in 35/76 (46.1%) cases. A total of 35/76 (46.1%) survived after 2 years; there was developmental delay in 9.2% of cases.
CONCLUSION
There is a large variation in the outcome of PFA depending upon the type of anomaly. Associated anomalies are common in VH and DWM, making their prognosis worse.
Topics: Female; Infant, Newborn; Child; Humans; Infant; Prevalence; Prospective Studies; Magnetic Resonance Imaging; Dandy-Walker Syndrome; Fetus; Cysts
PubMed: 36318816
DOI: 10.1111/jpc.16254 -
Pediatric Radiology Mar 2023Prenatal diagnoses of cystic malformations of the posterior fossa mainly encompass arachnoid cysts, Blake's pouch cysts and Dandy-Walker syndrome. To date, vermian cysts...
BACKGROUND
Prenatal diagnoses of cystic malformations of the posterior fossa mainly encompass arachnoid cysts, Blake's pouch cysts and Dandy-Walker syndrome. To date, vermian cysts have not been reported prenatally.
OBJECTIVES
To report a series of fetuses with a vermian cyst.
MATERIALS AND METHODS
This was a single-center retrospective study conducted from 2012 to 2021. We included all fetuses presenting with a vermian cyst and excluded all other types of posterior fossa cyst. The cyst was visible at prenatal ultrasound (US) and/or magnetic resonance imaging (MRI). Postnatal imaging and/or clinical outcome data were available.
RESULTS
Sixteen fetuses fulfilled the inclusion criteria with a strong female predominance (n=13). US and MRI were performed at a mean gestational age of 29+5 and 33+1 weeks, respectively. In all patients, the cyst was in the vermian horizontal fissure. The mean longest dimension was about 10 mm. The vermis and other posterior fossa structures were otherwise normal. At postnatal imaging, 13 children underwent brain imaging including 11 MRIs with complete regression (n=9), stability (n=1) and increase in size (n=3) of the cyst. Psychomotor development was normal in 14 children. One child (with an inner ear malformation) showed a slight delay in walking and language acquisition. Slight walking ataxia was present in another child.
CONCLUSION
We report 16 fetuses with posterior fossa cysts located within the vermis at the level of the horizontal fissure, diagnosed at US and/or MRI and carrying an overall excellent neurological prognosis.
Topics: Pregnancy; Child; Humans; Female; Infant; Male; Retrospective Studies; Prenatal Diagnosis; Dandy-Walker Syndrome; Cysts; Nervous System Malformations; Cranial Fossa, Posterior; Magnetic Resonance Imaging; Ultrasonography, Prenatal
PubMed: 36274068
DOI: 10.1007/s00247-022-05531-3 -
Journal of Taibah University Medical... Dec 2022Associations among Down syndrome (DS), Dandy-Walker variant (DWv), pulmonary hypertension (PH) and childhood interstitial lung disease (chILD) are extremely rare....
Associations among Down syndrome (DS), Dandy-Walker variant (DWv), pulmonary hypertension (PH) and childhood interstitial lung disease (chILD) are extremely rare. Several cases of trisomy disorders with Dandy-Walker malformation (DWM) and neurodevelopmental outcomes have been reported. The extent to which moderate to severe pulmonary hypertension with complications of patent ductus arteriosus (PDA), PH and chILD leads to substantial morbidity and mortality in infants with DS and DWM should be studied. We report the case of an ex-premature 15-month-old girl with confirmed DS with DWv, who developed PH and chILD. This is the first case study reporting the complexity of multiple associations involving DS and DWv. This case led to a prognostic dilemma and required compassionate parental counselling because of the child's uncertain future.
PubMed: 36212578
DOI: 10.1016/j.jtumed.2022.05.005 -
AJNR. American Journal of Neuroradiology Oct 2022The traditionally described Dandy-Walker malformation comprises a range of cerebellar and posterior fossa abnormalities with variable clinical severity. We aimed to...
BACKGROUND AND PURPOSE
The traditionally described Dandy-Walker malformation comprises a range of cerebellar and posterior fossa abnormalities with variable clinical severity. We aimed to establish updated imaging criteria for Dandy-Walker malformation on the basis of cerebellar development.
MATERIALS AND METHODS
In this multicenter study, retrospective MR imaging examinations from fetuses and children previously diagnosed with Dandy-Walker malformation or vermian hypoplasia were re-evaluated, using the choroid plexus/tela choroidea location and the fastigial recess shape to differentiate Dandy-Walker malformation from vermian hypoplasia. Multiple additional measures of the posterior fossa and cerebellum were also obtained and compared between Dandy-Walker malformation and other diagnoses.
RESULTS
Four hundred forty-six examinations were analyzed (174 fetal and 272 postnatal). The most common diagnoses were Dandy-Walker malformation (78%), vermian hypoplasia (14%), vermian hypoplasia with Blake pouch cyst (9%), and Blake pouch cyst (4%). Most measures were significant differentiators of Dandy-Walker malformation from non-Dandy-Walker malformation both pre- and postnatally (< .01); the tegmentovermian and fastigial recess angles were the most significant quantitative measures. Posterior fossa perimeter and vascular injury evidence were not significant differentiators pre- or postnatally (> .3). The superior posterior fossa angle, torcular location, and vermian height differentiated groups postnatally (< .01), but not prenatally (> .07).
CONCLUSIONS
As confirmed by objective measures, the modern Dandy-Walker malformation phenotype is best defined by inferior predominant vermian hypoplasia, an enlarged tegmentovermian angle, inferolateral displacement of the tela choroidea/choroid plexus, an obtuse fastigial recess, and an unpaired caudal lobule. Posterior fossa size and torcular location should be eliminated from the diagnostic criteria. This refined phenotype may help guide future study of the numerous etiologies and varied clinical outcomes.
Topics: Humans; Retrospective Studies; Dandy-Walker Syndrome; Cerebellum; Cysts; Neuroimaging; Magnetic Resonance Imaging; Cranial Fossa, Posterior
PubMed: 36137655
DOI: 10.3174/ajnr.A7659 -
European Journal of Medical Genetics Nov 2022Ritscher-Schinzel syndrome (RTSCS) is a rare genetic condition characterized by peculiar craniofacial features and cerebellar and cardiovascular malformations. To date,...
Ritscher-Schinzel syndrome (RTSCS) is a rare genetic condition characterized by peculiar craniofacial features and cerebellar and cardiovascular malformations. To date, four genes are implicated in this condition. The first two genes described were the autosomal recessive inherited gene WASHC5 associated with Ritscher-Schinzel syndrome 1 (RTSCS1), and CCDC22, an X-linked recessive gene causing Ritscher-Schinzel syndrome 2 (RTSCS2). In recent years, two other genes have been identified: VPS35L (RTSCS3) and DPYSL5 (RTSCS4). Only few patients with a molecular diagnosis of RTSCS have been reported, leaving the phenotypical spectrum and genotype-phenotype correlations ill-defined. We expand the number of genetically confirmed patients with RTSCS1 and 2; reporting three live born and three terminated pregnancies from two unrelated families. Four siblings carried compound heterozygous variants in WASHC5 while two siblings harboured a hemizygous CCDC22 variant. The most common findings in all patients were craniofacial dysmorphism, particularly macrocephaly, down slanted palpebral fissures and low set-ears. Developmental delay, intellectual disability and ataxic gait were present in all patients. One of the patients with the CCDC22 variant presented pubertas tarda. Elevation of nuchal translucency was observed in the first trimester ultrasound in three foetuses with compound heterozygous variants in WASHC5. None of the patients had epilepsy. The pre- and postnatal findings of this cohort expand the known phenotype of RTSCS1 and 2, with direct impact on postnatal outcome, management, and familial counseling.
Topics: Female; Humans; Pregnancy; Abnormalities, Multiple; Craniofacial Abnormalities; Dandy-Walker Syndrome; Heart Septal Defects, Atrial; Hydrolases; Microtubule-Associated Proteins; Phenotype; Proteins; Syndrome
PubMed: 36130690
DOI: 10.1016/j.ejmg.2022.104624