Diagnosis Of Cornelia De Lange Syndrome Research Articles

Cornelia De Lange Syndrome with left heart hypoplasia: a case study

Cornelia de Lange syndrome (CdLS) is characterized by slow growth that can lead to short stature. Despite mutations in the NIPBL, RAD21 or SMC3 genes, CdLS is thought to be inherited in an autosomal dominant manner. Findings include intellectual disability and bone abnormalities in the upper extremities and distinct facial features. It has similar characteristics to autism spectrum disorder, which is a developmental condition that affects communication and social interaction. The physical and clinical findings of a one-and-a-half-year-old girl patient diagnosed with CdLS were reported. In addition to NIPBL gene mutation, atrioventricular septal defect (AVSD), an overriding aorta, and a hypoplastic left heart (HLH) were observed in our case. This study revealed the patient's physical and clinical findings consistent with the diagnosis of CdLS. Additionally emphasized HLH. The importance of performing corrective surgery immediately following the evaluation of congenital heart diseases in CdLS patients can be emphasized.

Ophthalmologic findings in Cornelia de Lange syndrome

Introduction : Cornelia de Lange syndrome (CdLS) is a rare disease characterized by multisystem abnormalities, including various ophthalmologic problems. The purpose is to report this kind of rare case and highlight the role of ophthalmologist in visual development optimalization.
 Case Illustration : A 2-year-old boy with CdLS showing bilateral microcornea, cataracts with “dot opacities,” and chin lifts induced by ptosis. We also examined brow hypertrichosis, synophrys, and long arcuate eyelashes. High myopia and high astigmatism was found in the patient with spherical equivalent of 9.8 D. He was born with low birth weight, microcephaly, anteverted nostrils, depressed nasal bridge, thin upper lip, micrognathia, low posterior hairline, short neck, and syndactili. He also showed psychological lag and developmental impairment. Glasses was then prescribed to prevent amblyopia.
 Discussion : Individuals with CdLS may have multiple treatable ocular conditions. We recommend that patients have an initial ophthalmic examination after diagnosis of CdLS is first made, in order to establish a baseline and to assess for the presence of abnormalities that would benefit from early intervention. Examination under anesthesia may be required in some patients to adequately assess for any abnormalities, and to obtain a good refraction as well as an inspection of the retinal periphery in children with long axial length. Early intervention may greatly improve function and prevent vision loss due to amblyopia.
 Conclusion : Initial ophthalmic examination followed by routine annual screening is warranted when a diagnosis of CdLS is made, given that ocular anomalies are present in the majority of patients and may impact vision and daily functioning.

Loss-of-function HDAC8 mutations cause a phenotypic spectrum of Cornelia de Lange syndrome-like features, ocular hypertelorism, large fontanelle and X-linked inheritance

Cornelia de Lange syndrome (CdLS) is a multisystem genetic disorder with distinct facies, growth failure, intellectual disability, distal limb anomalies, gastrointestinal and neurological disease. Mutations in NIPBL, encoding a cohesin regulatory protein, account for >80% of cases with typical facies. Mutations in the core cohesin complex proteins, encoded by the SMC1A, SMC3 and RAD21 genes, together account for ∼5% of subjects, often with atypical CdLS features. Recently, we identified mutations in the X-linked gene HDAC8 as the cause of a small number of CdLS cases. Here, we report a cohort of 38 individuals with an emerging spectrum of features caused by HDAC8 mutations. For several individuals, the diagnosis of CdLS was not considered prior to genomic testing. Most mutations identified are missense and de novo. Many cases are heterozygous females, each with marked skewing of X-inactivation in peripheral blood DNA. We also identified eight hemizygous males who are more severely affected. The craniofacial appearance caused by HDAC8 mutations overlaps that of typical CdLS but often displays delayed anterior fontanelle closure, ocular hypertelorism, hooding of the eyelids, a broader nose and dental anomalies, which may be useful discriminating features. HDAC8 encodes the lysine deacetylase for the cohesin subunit SMC3 and analysis of the functional consequences of the missense mutations indicates that all cause a loss of enzymatic function. These data demonstrate that loss-of-function mutations in HDAC8 cause a range of overlapping human developmental phenotypes, including a phenotypically distinct subgroup of CdLS.

February 2010 Case Report: This Is a Case of Cornelia De Lange Syndrome

To the Editor I felt obliged to respond to the Case Report titled, “Association of Pericentric Inversion of Chromosome 9 (inv\[9\] \[p11q13\]) and Genetic Diseases: Case Report,” ( LabMed . 2010;41:96). According to the clinical features described by the authors and also obviously shown in the patient picture, I can assure that this infant is affected with Cornelia de Lange syndrome (CdLS). The clinical features of the patient mentioned in the article, “His remarkable clinical findings were growth retardation, small head, synophrys, long philtrum, micrognathia, hypospadias, low hairline, high arched palate, micropenis, and cryptorchidism,” all support the diagnosis of CdLS. It is well known that pericentric inversion of chromosome 9 is one of the most common balanced structural chromosomal aberrations found in 1% to … ohallioglu{at}mersin.edu.tr akbasetem{at}gmail.com

Cornelia de Lange syndrome associated with a de-novo novel NIPBL splice-site mutation and a coincidental inherited translocation t(3;5)(p13;q11)

Introduction The aim of this study was to evaluate a patient presenting dysmorphic features and multiorgan malformations suggestive of a severe Cornelia de Lange syndrome (CdLS) phenotype. Initial studies included classical karyotype and nipped-B homolog (NIPBL) mutational screening, which showed a translocation t(3;5)(p13;q11) and a novel sequence variant in the NIPBL gene. Further evaluation of the findings allowed the determination of their pathogenic significance and hence molecular confirmation of the diagnosis of CdLS.

Facial diagnosis of mild and variant CdLS: Insights from a dysmorphologist survey

Cornelia de Lange syndrome (CdLS) is a dominant disorder with classic severe forms and milder atypical variants. Central to making the diagnosis is identification of diagnostic facial features. With the recognition that patients with SMC1A and SMC3 mutations have milder, atypical features, we surveyed 65 dysmorphologists using facial photographs from 32 CdLS patients with the goals of (1) Illustrating examples of milder patients with SMC1A mutations and (2) Obtaining objective data to determine which facial features were useful and misleading in making a diagnosis of CdLS. Clinicians were surveyed whether the patient had CdLS or another diagnosis, the certainty of response and the clinical features used to support each response. Using only facial photographs, an average of 24 cases (75%) were accurately diagnosed per clinician. Correct diagnoses were made in 90% of classic CdLS and 87% of non-CdLS cases, however, only 54% of mild or variant CdLS were correctly diagnosed by respondents. We confirmed that CdLS is most accurately diagnosed in childhood and the diagnosis becomes increasingly difficult with age. This survey demonstrated that emphasis is placed on the eyebrows, nasal features, prominent upper lip and micrognathia. In addition, the presence of fuller, atypical eyebrows, a prominent nasal bridge and significant prognathism with age dissuaded survey takers from arriving at a diagnosis of CdLS in individuals with mild NIPBL and SMC1A mutations. This work underscores the difficulty in diagnosing patients with mild and variant CdLS and serves to objectively classify both useful and misleading features in the diagnosis of CdLS.

Cornelia de Lange Syndrome in association with a balanced reciprocal translocation involving chromosomes 3 and 5

We present a case report on a fetus with multiple malformations, diagnosed by ultrasound at 20 weeks' gestation. From the combination of intrauterine growth retardation and limb abnormalities that were observed, the most likely diagnosis was considered to be Cornelia de Lange Syndrome (CdLS). Following counselling, the mother opted to terminate the pregnancy. Chromosome analysis of cultured amniotic fluid cells showed a karyotype of 46,XX,t(3;5)(q21;p13). Postmortem examination of the baby confirmed the presence of features consistent with a diagnosis of CdLS. This case provides a report of a definitive diagnosis of Cornelia de Lange Syndrome, suspected on the basis of ultrasound imaging and confirmed by amniocentesis findings.