Evaluating Face2Gene as a Tool to Identify Cornelia de Lange Syndrome by Facial Phenotypes

Ana Latorre-Pellicer; Ángela Ascaso; Laura Trujillano; Marta Gil-Salvador; Maria Arnedo; Cristina Lucia-Campos; Rebeca Antoñanzas-Pérez; Iñigo Marcos-Alcalde; Ilaria Parenti; Gloria Bueno-Lozano; Antonio Musio; Beatriz Puisac; Frank J. Kaiser; Feliciano J. Ramos; Paulino Gómez-Puertas; Juan Pié

doi:10.3390/ijms21031042

Evaluating Face2Gene as a Tool to Identify Cornelia de Lange Syndrome by Facial Phenotypes

International Journal of Molecular Sciences ◽

10.3390/ijms21031042 ◽

2020 ◽

Vol 21 (3) ◽

pp. 1042 ◽

Cited By ~ 2

Author(s):

Ana Latorre-Pellicer ◽

Ángela Ascaso ◽

Laura Trujillano ◽

Marta Gil-Salvador ◽

Maria Arnedo ◽

...

Keyword(s):

Clinical Diagnosis ◽

Prediction Accuracy ◽

Genetic Diseases ◽

Clinical Score ◽

Cornelia De Lange Syndrome ◽

Computer Assisted ◽

Causal Genes ◽

Facial Pattern ◽

Computer Assisted Image ◽

Cornelia De Lange

Characteristic or classic phenotype of Cornelia de Lange syndrome (CdLS) is associated with a recognisable facial pattern. However, the heterogeneity in causal genes and the presence of overlapping syndromes have made it increasingly difficult to diagnose only by clinical features. DeepGestalt technology, and its app Face2Gene, is having a growing impact on the diagnosis and management of genetic diseases by analysing the features of affected individuals. Here, we performed a phenotypic study on a cohort of 49 individuals harbouring causative variants in known CdLS genes in order to evaluate Face2Gene utility and sensitivity in the clinical diagnosis of CdLS. Based on the profile images of patients, a diagnosis of CdLS was within the top five predicted syndromes for 97.9% of our cases and even listed as first prediction for 83.7%. The age of patients did not seem to affect the prediction accuracy, whereas our results indicate a correlation between the clinical score and affected genes. Furthermore, each gene presents a different pattern recognition that may be used to develop new neural networks with the goal of separating different genetic subtypes in CdLS. Overall, we conclude that computer-assisted image analysis based on deep learning could support the clinical diagnosis of CdLS.

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Clinical Diagnosis of Classical Cornelia de Lange Syndrome Made From Postmortem Examination of Second Trimester Fetus With Novel NIPBL Pathogenic Variant

Pediatric and Developmental Pathology ◽

10.1177/1093526619834429 ◽

2019 ◽

Vol 22 (5) ◽

pp. 475-479 ◽

Cited By ~ 1

Author(s):

Jennifer Hague ◽

Philip Twiss ◽

Zoe Mead ◽

Soo-Mi Park

Keyword(s):

Clinical Diagnosis ◽

Upper Limb ◽

Growth Retardation ◽

Postmortem Examination ◽

Pathogenic Variant ◽

Cornelia De Lange Syndrome ◽

Molecular Testing ◽

Intrauterine Death ◽

Second Trimester ◽

Cornelia De Lange

Classical Cornelia de Lange syndrome (CdLS) is a rare genetic disorder which is associated with distinctive facial features, growth retardation, significant intellectual disability and global developmental delay, hirsutism, and upper-limb reduction defects. Classical CdLS is associated with pathogenic variants in NIPBL. We present a clinical diagnosis of classical CdLS made in a second trimester male fetus with advanced maceration who had undergone intrauterine death at 15 + 6 weeks gestation. The diagnosis was suspected after multiple congenital anomalies were identified on fetal postmortem examination. These included intrauterine growth retardation, upper limb anomalies, ventricular septal defect and diaphragmatic hernia, and skeletal and genitourinary abnormalities. Related prenatal screening findings included a raised nuchal translucency and low maternal serum pregnancy-associated plasma protein-A. Targeted molecular sequencing of genes associated with CdLS identified a novel de novo frameshift pathogenic variant in NIPBL, which confirmed the diagnosis. This report describes our case and reviews the current literature on prenatal diagnosis of CdLS. In summary, we demonstrate that clinical diagnosis of CdLS in a second trimester fetus, through postmortem examination findings, is possible, with confirmation through molecular testing.

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PEDIA: Prioritization of Exome Data by Image Analysis

10.1101/473306 ◽

2018 ◽

Cited By ~ 1

Author(s):

Tzung-Chien Hsieh ◽

Martin Atta Mensah ◽

Jean Tori Pantel ◽

Krawitz Peter ◽

Dione Aguilar ◽

...

Keyword(s):

Image Analysis ◽

Diagnostic Yield ◽

Value Added ◽

Computer Assisted ◽

Exome Data ◽

Monogenic Disorders ◽

Facial Pattern ◽

Computer Assisted Image ◽

Portrait Photographs ◽

Assisted Analysis

AbstractPhenotype information is crucial for the interpretation of genomic variants. So far it has only been accessible for bioinformatics workflows after encoding into clinical terms by expert dysmorphologists. Here, we introduce an approach, driven by artificial intelligence that uses portrait photographs for the interpretation of clinical exome data. We measured the value added by computer-assisted image analysis to the diagnostic yield on a cohort consisting of 679 individuals with 105 different monogenic disorders. For each case in the cohort we compiled frontal photos, clinical features and the disease-causing mutations and simulated multiple exomes of different ethnic backgrounds. With the additional use of similarity scores from computer-assisted analysis of frontal photos, we were able to achieve a top-10-accuracy rate for the disease-causing gene of 99 %. As this performance is significantly higher than without the information from facial pattern recognition, we make gestalt scores available for prioritization via an API.

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Clinical score of 62 Italian patients with Cornelia de Lange syndrome and correlations with the presence and type ofNIPBLmutation

Clinical Genetics ◽

10.1111/j.1399-0004.2007.00832.x ◽

2007 ◽

Vol 72 (2) ◽

pp. 98-108 ◽

Cited By ~ 70

Author(s):

A Selicorni ◽

S Russo ◽

C Gervasini ◽

P Castronovo ◽

D Milani ◽

...

Keyword(s):

Clinical Score ◽

Cornelia De Lange Syndrome ◽

Cornelia De Lange

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A 16-Day-Old Infant with a Clinical Diagnosis of Classical Cornelia de Lange Syndrome

Case Reports in Pediatrics ◽

10.1155/2020/6482938 ◽

2020 ◽

Vol 2020 ◽

pp. 1-4

Author(s):

Pamela Rodríguez ◽

Karla Asturias

Keyword(s):

Clinical Diagnosis ◽

Genetic Disorder ◽

Molecular Genetic ◽

Male Infant ◽

Cornelia De Lange Syndrome ◽

Clinical Criteria ◽

Limb Reduction ◽

Regulator Genes ◽

Craniofacial Features ◽

Cornelia De Lange

Cornelia de Lange syndrome (CdLS) is a rare syndromic genetic disorder characterized by multiple congenital anomalies with upper limb reduction defects, along with cardiac, gastrointestinal, and genitourinary defects. It is caused by genetic variations in the chromatin regulator genes, most commonly, the cohesin complex. Even though molecular genetic testing is highly recommended to confirm the diagnosis, high costs and unavailability in some settings are significant setbacks, and clinical criteria could be used. The typical craniofacial features include generalized hirsutism, synophrys, microbrachycephaly, highly arched eyebrows, and long eyelashes, along with height and weight below the 5th percentile. In this paper, we present a case of a 16-day-old male infant in whom a clinical diagnosis of classical CdLS was made.

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High Rate of Autonomic Neuropathy in Cornelia De Lange Syndrome

10.21203/rs.3.rs-534763/v1 ◽

2021 ◽

Author(s):

Maria Jesus Pablo ◽

Pilar Pamplona ◽

Maria Haddad ◽

Isabel Benavente ◽

Ana Latorre-Pellicer ◽

...

Keyword(s):

Nervous System ◽

Sensory Nerve ◽

Growth Failure ◽

Sympathetic Skin Response ◽

Clinical Score ◽

Premature Aging ◽

High Rate ◽

Cornelia De Lange Syndrome ◽

Skin Response ◽

Cornelia De Lange

Abstract BackgroundCornelia de Lange Syndrome (CdLS) is a rare congenital disorder characterized by typical facial features, growth failure, limb abnormalities, and gastroesophageal dysfunction that may be caused by mutations in several genes that disrupt gene regulation early in development. Symptoms in individuals with CdLS suggest that the peripheral nervous system (PNS) is involved, yet there is little direct evidence.MethodSomatic nervous system was evaluated by conventional motor and sensory nerve conduction studies and autonomic nervous system by heart rate variability, sympathetic skin response and sudomotor testing. CdLS Clinical Score and genetic studies were also obtained.ResultsSympathetic skin response and sudomotor test were pathological in 35% and 34% of the individuals with CdLS, respectively. Nevertheless, normal values in large fiber nerve function studies.ConclusionsAutonomic nervous system (ANS) dysfunction is found in many individuals with Cornelia de Lange syndrome, and could be related to premature aging.

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Computer Assisted Image Reconstruction of Oligomer Structure

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100092323 ◽

1976 ◽

Vol 34 ◽

pp. 472-473

Author(s):

A.M. Jones ◽

A. Max Fiskin

Keyword(s):

Three Dimensional ◽

Depth Of Field ◽

Computer Assisted ◽

Projection Data ◽

Two Dimensional ◽

Single Particles ◽

Dimensional Reconstruction ◽

Computer Assisted Image ◽

The Fourier Transform ◽

Space Approach

If the tilt of a specimen can be varied either by the strategy of observing identical particles orientated randomly or by use of a eucentric goniometer stage, three dimensional reconstruction procedures are available (l). If the specimens, such as small protein aggregates, lack periodicity, direct space methods compete favorably in ease of implementation with reconstruction by the Fourier (transform) space approach (2). Regardless of method, reconstruction is possible because useful specimen thicknesses are always much less than the depth of field in an electron microscope. Thus electron images record the amount of stain in columns of the object normal to the recording plates. For single particles, practical considerations dictate that the specimen be tilted precisely about a single axis. In so doing a reconstructed image is achieved serially from two-dimensional sections which in turn are generated by a series of back-to-front lines of projection data.

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New polarized-light microscope for fast and orientation independent measurement of birefringent fine structure

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100146254 ◽

1993 ◽

Vol 51 ◽

pp. 82-83

Author(s):

Rudolf Oldenbourg

Keyword(s):

Light Microscope ◽

Polarized Light ◽

Video Camera ◽

Limited Range ◽

Image Point ◽

Computer Assisted ◽

Optical Modulators ◽

Anisotropic Structures ◽

Long Time ◽

Computer Assisted Image

The polarized light microscope has the unique potential to measure submicroscopic molecular arrangements dynamically and non-destructively in living cells and other specimens. With the traditional pol-scope, however, single images display only those anisotropic structures that have a limited range of orientations with respect to the polarization axes of the microscope. Furthermore, rapid measurements are restricted to a single image point or single area that exhibits uniform birefringence or other form of optical anisotropy, while measurements comparing several image points take an inordinately long time.We are developing a new kind of polarized light microscope which combines speed and high resolution in its measurement of the specimen anisotropy, irrespective of its orientation. The design of the new pol-scope is based on the traditional polarized light microscope with two essential modifications: circular polarizers replace linear polarizers and two electro-optical modulators replace the traditional compensator. A video camera and computer assisted image analysis provide measurements of specimen anisotropy in rapid succession for all points of the image comprising the field of view.

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