Molecular confirmation of nine cases of Cornelia de Lange syndrome diagnosed prenatally

Dempsey, Melissa A; Johnson, Anthony; Swope, B. S.; Moldenhauer, Julie S.; Sroka, Hana; Chitayat, David; Briere, Lauren C.; Lyon, Helen N.; Palmer, Nickie; Gopalani, Sameer Vali; Siebert, Joseph R.; Levesque, Sébastien; Leblanc, Jean-Pierre; Menzies, Donald; Haverfield, Eden; Das, Soma

doi:10.1002/pd.4279

Cited by 15 publications

(11 citation statements)

References 34 publications

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“…No large studies have been performed to determine gene-based familial recurrence risks in CdLS. Infrequently, families in which non-classic CdLS segregates in an autosomal dominant manner have been reported, as has germline mosaicism leading to affected siblings born to unaffected parents 47,48 50 . Limb anomalies were seen in 66% of fetuses (likely representing a selection bias), and approximately 50% of fetuses had an abnormal facial profile (micrognathia and prominent maxilla) 51 .…”

Section: Familial Recurrence Riskmentioning

confidence: 99%

Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement

et al. 2018

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Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning.

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Section: Familial Recurrence Riskmentioning

confidence: 99%

Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement

et al. 2018

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“…To date 333 different heterozygous NIPBL mutations have been identified in 391 CdLS patients, 28 of whom belong to 13 families (43-45); 278 of these mutations were compiled in an excellent recent review and subsequently 55 further novel mutations have been identified (43)(44)(45)(46)(47)(48).…”

Section: The Genetic Basis Of Cdlsmentioning

confidence: 99%

Cornelia de Lange syndrome

et al. 2014

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Cornelia de Lange syndrome (CdLS; MIM #122470, 300590, 610759, 614701, 300882) is a rare and clinically variable disorder that affects multiple organs. It is characterized by intellectual disability (mild to severe), distinctive facial features, prenatal and postnatal growth retardation, and hirsutism. Congenital anomalies include malformations of the upper limbs, gastrointestinal malformation/rotation, pyloric stenosis, diaphragmatic hernia, heart defects and genitourinary malformations. Gastroesophageal reflux disease is present in almost all patients. In addition to classic forms, milder phenotypes have been reported. To date five genes [NIPBL (Nipped-B-like protein), SMC1A (structural maintenance of chromosomes 1A), SMC3 (structural maintenance of chromosomes 3), RAD21 (human homolog of Schizosaccharomyces pombe radiation sensitive mutant 21) and HDAC8 (histone deacetylase 8)] have been associated with CdLS and mutations of these genes comprise the underlying defect in 70% of the patients. Here, we will provide a brief review of the clinical features of CdLS, summarize the known underlying genetic defects, prenatal and postnatal diagnosis possibilities, and genetic counseling.

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“…Chromosomal abnormalities, cardiac malformations, and many genetic syndromes have been associated with an increased thickness of NT. Previous studies reported an abnormal thickness of NT in the first trimester (Dempsey et al, ) at 11 (Sekimoto et al, ; Huang and Porto, ) and 12 (Bruner and Hsia, ) weeks of gestation, in cases with a normal karyotype and postnatally diagnosed as affected by CdLS. On the other hand, affected cases with normal first trimester NT have also been reported (Chong et al, ; Kanellopoulos et al, ; Sepulveda et al, ; Weichert, ; Clark et al, ; Spaggiari et al, ; Dempsey et al, ), suggesting that NT values may not be considered a specific early marker of CdLS.…”

Section: Nuchal Translucencymentioning

confidence: 91%

Cornelia de Lange syndrome: To diagnose or not to diagnose in utero?

Avagliano

Bulfamante

Massa

2017

Birth Defects Research

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Cornelia de Lange syndrome (CdLS) is an inherited condition with a wide spectrum of phenotypic anomalies, consisting mainly of growth impairment, multi‐organ abnormalities, and neurocognitive delay. Clinical diagnostic criteria after birth are well defined, whereas when to suspect the syndrome during intrauterine life still remains undefined. This review summarizes the main possible prenatal findings in CdLS, suggesting that a skilled ultrasound scan in cases of intrauterine growth restriction associated with other fetal abnormalities may improve the chance of prenatal diagnosis of CdLS, especially in families known to be at high risk. We propose that, following a sequence of detailed scans and examinations, CdLS affected fetuses could be diagnosed in utero, when one or more conditions (among them, intrauterine growth restriction, limb defects, facial abnormalities, diaphragmatic hernia, and heart diseases) are detected, and possibly confirmed by specific molecular testing. Birth Defects Research 109:771–777, 2017. © 2017 The Authors. Birth Defects Research Published by Wiley Periodicals, Inc.

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Molecular confirmation of nine cases of Cornelia de Lange syndrome diagnosed prenatally

Abstract: We demonstrate that prenatally-detected phenotypes of CdLS, particularly severe micrognathia and bilateral upper limb defects, are associated with an increased frequency of NIPBL mutations.

Cited by 15 publications

References 34 publications

Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement

Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement

Cornelia de Lange syndrome

Cornelia de Lange syndrome: To diagnose or not to diagnose in utero?

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