title: Two cases of Legg-Perthes and intellectual disability in Tricho-Rhino-Phalangeal syndrome type 1 associated with novel TRPS1 mutations.
abstract: Tricho-Rhino-Phalangeal syndrome is a rare autosomal dominant genetic disorder caused by mutations in the TRPS1 gene. This malformation syndrome is characterized by distinctive craniofacial features including sparse scalp hair, bulbous tip of the nose, long flat philtrum, thin upper vermilion border, and protruding ears. Skeletal abnormalities include cone-shaped epiphyses at the phalanges, hip malformations, and short stature. In this report, we describe two patients with the physical manifestations and genotype of TRPS type I but with learning/intellectual disability not typically described as part of the syndrome. The first patient has a novel heterozygous two-base-pair deletion of nucleotides at 3198-3199 (c.3198-3199delAT) in the TRPS1 gene causing a translational frameshift and subsequent alternate stop codon. The second patient has a 3.08 million base-pair interstitial deletion at 8q23.3 (113,735,487-116,818,578), which includes the TRPS1 gene and CSMD3. Our patients have characteristic craniofacial features, Legg-Perthes syndrome, various skeletal abnormalities including cone shaped epiphyses, anxiety (first patient), and intellectual disability, presenting unusual phenotypes that add to the clinical spectrum of the disease.
authors.affiliation: Section of Medical Genetics, SUNY Upstate Medical University, Syracuse, New York.
authors.forename: Jordana L
authors.identifier: http://orcid.org/0000-0001-5828-397X
authors.initials: JL
authors.lastname: Gilman
authors.affiliation: Department of Pediatrics, Division of Genetic and Genomic Medicine, University of California, Irvine, Orange, California.
authors.forename: Heather A
authors.initials: HA
authors.lastname: Newman
authors.affiliation: Department of Pediatrics, Division of Genetic and Genomic Medicine, University of California, Irvine, Orange, California.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Freeman
authors.affiliation: Department of Pediatrics, Division of Genetic and Genomic Medicine, University of California, Irvine, Orange, California.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Singh
authors.affiliation: Department of Pediatrics, Division of Genetic and Genomic Medicine, University of California, Irvine, Orange, California.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Puckett
authors.affiliation: Division of Family Medicine, School of Medicine, University of California, Irvine, California.
authors.forename: David K
authors.initials: DK
authors.lastname: Morohashi
authors.affiliation: Section of Medical Genetics, SUNY Upstate Medical University, Syracuse, New York.
authors.forename: Constance
authors.initials: C
authors.lastname: Stein
authors.affiliation: Department of Orthopedic Surgery, SUNY Upstate Medical University, Syracuse, New York.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Palomino
authors.affiliation: Section of Medical Genetics, SUNY Upstate Medical University, Syracuse, New York.
authors.forename: Robert Roger
authors.initials: RR
authors.lastname: Lebel
authors.affiliation: Department of Pediatrics, Division of Genetic and Genomic Medicine, University of California, Irvine, Orange, California.
authors.forename: Virginia E
authors.initials: VE
authors.lastname: Kimonis
mesh_terms: D000293:Adolescent; D000328:Adult; D004268:DNA-Binding Proteins / Q000235:genetics*; D004413:Dysostoses / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008607:Intellectual Disability / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D007873:Legg-Calve-Perthes Disease / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D010009:Osteochondrodysplasias / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D012097:Repressor Proteins; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D012097:Repressor Proteins; C108387:TRPS1 protein, human; D014157:Transcription Factors
keywords: Legg-Perthes; TRPS1; Tricho-Rhino-Phalangeal syndrome type 1; cone shaped epiphyses