Next-generation phenotyping using computer vision algorithms in rare genomic neurodevelopmental disorders

• Published in: Genetics in medicine Vol. 21; no. 8; pp. 1719 - 1725
• Main Authors: van der Donk, Roos, Jansen, Sandra, Schuurs-Hoeijmakers, Janneke H. M., Koolen, David A., Goltstein, Lia C. M. J., Hoischen, Alexander, Brunner, Han G., Kemmeren, Patrick, Nellåker, Christoffer, Vissers, Lisenka E. L. M., de Vries, Bert B. A., Hehir-Kwa, Jayne Y.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2019; Elsevier Limited
• Subjects: Abnormalities, Multiple - diagnosis; Abnormalities, Multiple - genetics; Abnormalities, Multiple - physiopathology; Adolescent; Adult; Algorithms; Biomedical and Life Sciences; Biomedicine; Child; Child, Preschool; Chromosome Deletion; Chromosomes, Human, Pair 17 - genetics; Computer vision; Craniofacial Abnormalities - diagnosis; Craniofacial Abnormalities - genetics; Craniofacial Abnormalities - physiopathology; Facial Recognition; Female; Genomics; Human Genetics; Humans; Image Processing, Computer-Assisted; Infant; Intellectual Disability - diagnosis; Intellectual Disability - genetics; Intellectual Disability - physiopathology; Intracellular Signaling Peptides and Proteins - genetics; Laboratory Medicine; Male; Middle Aged; Muscular Atrophy - diagnosis; Muscular Atrophy - genetics; Muscular Atrophy - physiopathology; Musculoskeletal Abnormalities - diagnosis; Musculoskeletal Abnormalities - genetics; Musculoskeletal Abnormalities - physiopathology; Mutation, Missense - genetics; Neurodevelopmental disorders; Neurodevelopmental Disorders - diagnosis; Neurodevelopmental Disorders - genetics; Neurodevelopmental Disorders - physiopathology; Phenotype; Protein Phosphatase 2C - genetics; Vesicular Transport Proteins - genetics; Young Adult; facial image processing; phenotyping; facial phenotyping
• ISSN: 1098-3600; 1530-0366; 1530-0366
• DOI: 10.1038/s41436-018-0404-y

Purpose The interpretation of genetic variants after genome-wide analysis is complex in heterogeneous disorders such as intellectual disability (ID). We investigate whether algorithms can be used to detect if a facial gestalt is present for three novel ID syndromes and if these techniques can help interpret variants of uncertain significance. Methods Facial features were extracted from photos of ID patients harboring a pathogenic variant in three novel ID genes ( PACS1 , PPM1D , and PHIP ) using algorithms that model human facial dysmorphism, and facial recognition. The resulting features were combined into a hybrid model to compare the three cohorts against a background ID population. Results We validated our model using images from 71 individuals with Koolen–de Vries syndrome, and then show that facial gestalts are present for individuals with a pathogenic variant in PACS1 ( p  = 8 × 10 −4 ), PPM1D ( p  = 4.65 × 10 −2 ), and PHIP ( p  = 6.3 × 10 −3 ). Moreover, two individuals with a de novo missense variant of uncertain significance in PHIP have significant similarity to the expected facial phenotype of PHIP patients ( p  < 1.52 × 10 −2 ). Conclusion Our results show that analysis of facial photos can be used to detect previously unknown facial gestalts for novel ID syndromes, which will facilitate both clinical and molecular diagnosis of rare and novel syndromes.