D Chitayat

Mount Sinai Hospital, Toronto, Toronto, Ontario, Canada

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Publications (191)632.87 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Robinow Syndrome (RS), a rare skeletal dysplasia syndrome, is characterized by dysmorphic features resembling a fetal face, mesomelic limb shortening, hypoplastic external genitalia in males, and renal and vertebral anomalies. Both autosomal dominant and autosomal recessive patterns of inheritance have been reported. Since the description of autosomal dominant Robinow Syndrome (ADRS; OMIM 180700) in 1969 by Meinhard Robinow and colleagues, the molecular etiology remained elusive until only recently. WNT5A was proposed to be the candidate gene for ADRS, as mutations were found in two affected families, one of those being the originally described index family. We report three families with RS caused by novel heterozygous WNT5A mutations, which were confirmed in the first family by whole exome sequencing, and in all by Sanger sequencing. To our knowledge, this is the largest number of published families with ADRS in whom a WNT5A mutation was identified. Families 1 and 2 are the first cases showing de novo inheritance in the affected family members and thus strengthen the evidence for WNT5A as the causative gene in ADRS. Finally, we propose WNT5A mutation specificity in ADRS, which may affect interactions with other proteins in the Wnt pathway.
    Clinical Genetics 04/2014; · 4.25 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE:Diffusion-weighted imaging can be used to characterize brain maturation. MR imaging of the fetus is used in cases of suspected Chiari II malformation when further evaluation of the posterior fossa is required. We sought to investigate whether there were any quantitative ADC abnormalities of the cerebellum in fetuses with this malformation.MATERIALS AND METHODS:Measurements from ROIs acquired in each cerebellar hemisphere and the pons were obtained from calculated ADC maps performed on our Avanto 1.5T imaging system. Values in groups of patients with Chiari II malformations were compared with those from fetuses with structurally normal brains, allowing for the dependent variable of GA by using linear regression analysis.RESULTS:There were 8 fetuses with Chiari II malformations and 23 healthy fetuses, ranging from 20 to 31 GW. There was a significant linear decline in the cerebellar ADC values with advancing gestation in our healthy fetus group, as expected. The ADC values of the cerebellum of fetuses with Chiari II malformation were higher [1820 (±100) × 10(-6) mm(2)/s] than ADC values in the healthy fetuses (1370 ± 70) × 10(-6) mm(2)/s. This was statistically significant, even when allowing for the dependent variable of GA (P = .0126). There was no significant difference between the pons ADC values in these groups (P = .645).CONCLUSIONS:While abnormal white matter organization or early cerebellar degeneration could potentially contribute to our findings, the most plausible explanation pertains to abnormalities of CSF drainage in the posterior fossa, with increased extracellular water possibly accounting for this phenomenon.
    American Journal of Neuroradiology 05/2013; · 3.17 Impact Factor
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    ABSTRACT: Mutations in the FKRP gene account for a broad spectrum of patients ranging from CMD to a much milder LGMD2I. The involvement of the eyes can be variable with most patients having normal eye examination. We describe eye abnormalities in a child with Walker–Warburg phenotype due to a novel FKRP gene mutation in exon 3 and compare these with other reported cases with FKRP mutation. A boy was born to a G6P3L2 woman from Ghana. The couple was non-consanguineous and a previous pregnancy was interrupted for occipital encephalocele. Antenatal ultrasound showed severe hydrocephalus and delivery was by caesarian section at term. He had hypotonia, bilateral elbow contractures and very limited spontaneous movements. His creatine kinase was 6664 IU/L. Brain MRI showed massive hydrocephalus, diffuse cobblestone lissencephaly, hypomyelination, cerebellar cortical dysplasia, hypoplastic pons and deformed brainstem with fusion of colliculi. Eye examination revealed right micropthalmia, nonreactive pupils, absent red reflex, very deep anterior chamber with retrolental fibrovascular tissue. B scan showed closed funnel and total retinal unattachment. The left eye had shallow anterior chamber, tunica vasculosa lentis and clear lens, persistent vascular membrane, hypoplastic optic nerve, retinal pigmentary epithelium and vitreous hemorrhage. Fluorescein angiography revealed large areas of capillary dropouts and non perfusion ischemic retina. DNA testing showed two mutations in the FKRP gene: Exon 3:c.558dupC (p.Ala187fs) and Exon 3:c.1418T>G (p.Phe473cys).Patients with FKRP gene mutation have no or mild eye involvement (strabismus) with very few cases reported with moderate to severe eye involvement. Our patient represents one of the most severe phenotypes described in regards to eye involvement.
    Neuromuscular Disorders 10/2012; 22(s 9–10):815. · 3.46 Impact Factor
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    K. Fong, S. Blaser, J. Drake, D. Chitayat
    Ultrasound in Obstetrics and Gynecology 10/2011; 38(S1). · 3.56 Impact Factor
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    Ultrasound in Obstetrics and Gynecology 10/2011; 38(S1). · 3.56 Impact Factor
  • Ultrasound in Obstetrics and Gynecology 10/2010; 36(4):521-2. · 3.56 Impact Factor
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    ABSTRACT: Congenital megalourethra is a rare urogenital malformation characterized by dilation and elongation of the penile urethra associated with absence or hypoplasia of the corpora spongiosa and cavernosa. Postnatal complications include voiding and erectile dysfunction as well as renal insufficiency and pulmonary hypoplasia. To date, only a few prenatally diagnosed cases have been reported. We report on 10 cases diagnosed prenatally and their postnatal/autopsy findings. The study involved retrospective chart review of all cases diagnosed antenatally in three tertiary care centers over 5 years. Antenatal ultrasound images and medical records from obstetrics, genetics, urology and nephrology were reviewed. Ten fetuses with megalourethra were identified at a median gestational age of 19 (range, 13-24) weeks and all were confirmed postnatally or at autopsy. Three pregnancies were terminated and seven continued. All cases presented with a distended bladder and megalourethra and all cases had normal karyotype. Of seven liveborn babies, one died neonatally of pulmonary hypoplasia. All six infants alive at the time of writing had a dysfunctional urethra and three suffered from impaired or end-stage renal disease. Associated anomalies were found in half of the cases. Congenital megalourethra is caused by abnormal development or hypoplasia of the penile erectile tissue, secondary to distal urethral obstruction. When the amniotic fluid volume is normal, survival is possible. However, all liveborn infants have voiding and renal dysfunction and sexual dysfunction is expected. Megalourethra should be considered in all male fetuses presenting prenatally with megacystis and detailed fetal ultrasonography should look for an elongated and/or distended phallic structure as well as any associated anomalies.
    Ultrasound in Obstetrics and Gynecology 10/2010; 37(6):678-83. · 3.56 Impact Factor
  • A Toi, K Fong, D Chitayat, P Shannon, S Blaser
    Ultrasound in Obstetrics and Gynecology 10/2010; 36(S1):24. · 3.56 Impact Factor
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    ABSTRACT: The objective was to determine the risk of sampling error in amniocentesis and chorionic villus sampling (CVS) in singleton and multiple pregnancies. Data from this and other published studies were used to discuss current practice guidelines for molecular identity testing. Clinical and laboratory records of all patients undergoing molecular-based identity testing in our clinical laboratory from July 2002 until March 2008 were reviewed. DNA microsatellite testing was performed to determine zygosity in multiple pregnancies and maternal cell contamination (MCC) in both singleton and multiple pregnancies. MCC was detected in 6/148 (4%) CVS and 1/87 (1%) amniotic fluids from singleton pregnancies. In two of the CVS, only maternal cells were found. In 2/24 (8%) twin pregnancies, the same fetus was tested twice. In a total of 285 pregnancies (235 singleton, 24 twin, 26 with >or= 3 fetuses), without molecular identity testing, four women would have received erroneous results. Current guidelines recommend molecular identity testing for MCC in conjunction with molecular diagnostic testing, but not for cytogenetic testing. No published guidelines were found for zygosity testing in multiple pregnancies. We suggest that identity testing be considered for all prenatal testing of multiple pregnancies, especially if CVS is performed.
    Prenatal Diagnosis 08/2010; 30(8):746-52. · 2.68 Impact Factor
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    D Chitayat, P Glanc
    Ultrasound in Obstetrics and Gynecology 06/2010; 35(6):637-46. · 3.56 Impact Factor
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    ABSTRACT: Ciliary disorders share typical features, such as polydactyly, renal and biliary cystic dysplasia, and retinitis pigmentosa, which often overlap across diagnostic entities. We report on two siblings of consanguineous parents and two unrelated children, both of unrelated parents, with co-occurrence of Joubert syndrome and Jeune asphyxiating thoracic dystrophy, an association that adds to the observation of common final patterns of malformations in ciliary disorders. Using homozygosity mapping in the siblings, we were able to exclude all known genes/loci for both syndromes except for INVS, AHI1, and three genes from the previously described Jeune locus at 15q13. No pathogenic variants were found in these genes by direct sequencing. In the third child reported, sequencing of RPGRIP1L, ARL13B, AHI1, TMEM67, OFD1, CC2D2A, and deletion analysis of NPHP1 showed no mutations. Although this study failed to identify a mutation in the patients tested, the co-occurrence of Joubert and Jeune syndromes is likely to represent a distinct entity caused by mutations in a yet to be discovered gene. The mechanisms by which certain organ systems are affected more than others in the spectrum of ciliary diseases remain largely unknown.
    American Journal of Medical Genetics Part A 06/2010; 152A(6):1411-9. · 2.30 Impact Factor
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    ABSTRACT: No Abstracts.
    Ultrasound in Obstetrics and Gynecology 03/2010; 36(1):121-4. · 3.56 Impact Factor
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    Ultrasound in Obstetrics and Gynecology 01/2010; 35(1):119-20. · 3.56 Impact Factor
  • Ultrasound in Obstetrics & Gynecology - ULTRASOUND OBSTET GYN. 01/2010;
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    ABSTRACT: Background: Deletions that encompass 2q31.1 have been proposed as a microdeletion syndrome with common clinical features, including intellectual disability/developmental delay, microcephaly, cleft palate, growth delay, and hand/foot anomalies. In addition, several genes within this region have been proposed as candidates for split hand-foot malformation 5 (SHFM5). Methods: To delineate the genotype-phenotype correlation between deletions of this region, we identified 14 individuals with deletions at 2q31.1 detected by microarray analysis for physical and developmental disabilities. Results: All subjects for whom detailed clinical records were available had neurological deficits of varying degree. Seven subjects with deletions encompassing the HOXD cluster had hand/foot anomalies of varying severity, including syndactyly, brachydactyly, and ectrodactyly. Of 7 subjects with deletions proximal to the HOXD cluster, 5 of which encompassed DLX1/DLX2, none had clinically significant hand/foot anomalies. In contrast to previous reports, the individuals in our study did not display a characteristic gestalt of dysmorphic facial features. Conclusion: The absence of hand/foot anomalies in any of the individuals with deletions of DLX1/DLX2 but not the HOXD cluster supports the hypothesis that haploinsufficiency of the HOXD cluster, rather than DLX1/DLX2, accounts for the skeletal abnormalities in subjects with 2q31.1 microdeletions.
    Molecular syndromology 01/2010; 1(5):262-271.
  • Clinical Biochemistry - CLIN BIOCHEM. 01/2010; 43(9):783-783.
  • C M Roifman, D Chitayat
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    ABSTRACT: Combined immunodeficiency (SCID) can be isolated and involve the immune system only or associated with abnormalities affecting other organs, mainly the skeletal and neurological systems. We report on sisters, born to consanguineous parents, with CID, facial dysmorphism, developmental delay, optic atrophy, myoclonic seizures, and skeletal anomalies. To the best of our knowledge, this is a hitherto new syndrome with most probably autosomal recessive inheritance and unknown etiology.
    Clinical Genetics 11/2009; 76(5):449-57. · 4.25 Impact Factor
  • Ultrasound in Obstetrics and Gynecology 10/2009; 34(S1):243. · 3.56 Impact Factor
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    ABSTRACT: Screening studies for trisomy 21 demonstrate that low maternal serum pregnancy-associated plasma protein-A (PAPP-A) at 11-13 weeks' gestation is associated with stillbirth, intrauterine growth restriction (IUGR) and pre-eclampsia in chromosomally normal fetuses. However, the strength of these associations is too weak to justify screening for these placental insufficiency syndromes. Our objective was to evaluate placental size and uterine artery (UtA) Doppler imaging as second-stage screening tests for women with low PAPP-A. We prospectively studied 90 normal singleton pregnancies with first-trimester PAPP-A </= 0.30 multiples of the median. Maternal serum alpha-fetoprotein (AFP) at 15-18 weeks' gestation, and second-trimester placental size and UtA Doppler indices were assessed as predictors of pregnancy outcome. The risks of IUGR, preterm delivery before 32 weeks' gestation and stillbirth were significantly associated with small placental size (relative risk (RR), 3.96; 95% CI, 2.21-5.98; RR, 3.96; 95% CI, 2.21-5.98; and RR, 6.44, 95% CI, 2.74-14.54, respectively) and elevated AFP (RR, 3.67; 95% CI, 1.78-7.71; RR, 2.48; 95% CI, 1.23-4.94; and RR, 5.14; 95% CI, 1.66-16.85, respectively), but not with abnormal UtA Doppler indices. The combination of elevated AFP and small placental size further increased the risk of IUGR (RR, 4.88; 95% CI, 2.88-5.31), delivery before 32 weeks' gestation (RR, 4.25; 95% CI, 2.38-4.98) and stillbirth (RR, 7.44; 95% CI, 3.04-3.75). Small placental size and elevated AFP, but not UtA Doppler indices, identify women with low PAPP-A at high risk of IUGR, extreme preterm delivery and stillbirth. These additional screening tests may directly improve perinatal outcomes in women with low PAPP-A.
    Ultrasound in Obstetrics and Gynecology 09/2009; 34(3):274-82. · 3.56 Impact Factor

Publication Stats

4k Citations
632.87 Total Impact Points


  • 1994–2014
    • Mount Sinai Hospital, Toronto
      • Department of Obstetrics and Gynecology
      Toronto, Ontario, Canada
    • Toronto Western Hospital
      Toronto, Ontario, Canada
  • 1993–2012
    • SickKids
      • • Division of Clinical and Metabolic Genetics
      • • Department of Paediatrics
      • • Clinical Genetics Program
      • • Division of Clinical Pharmacology and Toxicology
      Toronto, Ontario, Canada
  • 1993–2011
    • University of Toronto
      • • Division of Clinical and Metabolic Genetics
      • • Department of Obstetrics and Gynaecology
      • • Department of Paediatrics
      • • Department of Laboratory Medicine and Pathobiology
      • • Division of Cardiology
      Toronto, Ontario, Canada
  • 2008
    • University College Dublin
      • School of Medicine & Medical Science
      Dublin, L, Ireland
  • 2007
    • Hebrew University of Jerusalem
      • Human Genetics Center
      Jerusalem, Jerusalem District, Israel
  • 2001–2007
    • Mount Sinai Hospital
      New York City, New York, United States
  • 2005
    • National Maternity Hospital
      Dublin, Leinster, Ireland
  • 2000
    • Women's College Hospital
      Toronto, Ontario, Canada
  • 1999
    • Case Western Reserve University School of Medicine
      Cleveland, Ohio, United States
  • 1995–1998
    • UHN: Toronto General Hospital
      Toronto, Ontario, Canada
  • 1991–1993
    • McGill University
      • Department of Pediatrics
      Montréal, Quebec, Canada
  • 1988–1993
    • University of British Columbia - Vancouver
      • Department of Medical Genetics
      Vancouver, British Columbia, Canada
  • 1987–1990
    • Albert Einstein College of Medicine
      • Department of Pediatrics
      New York City, NY, United States
    • Montefiore Medical Center
      New York City, New York, United States
  • 1989
    • Vancouver General Hospital
      Vancouver, British Columbia, Canada
  • 1988–1989
    • Grace Hospital
      Winnipeg, Manitoba, Canada