RESUMO
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.
Assuntos
Proteínas de Ligação a DNA/genética , Disostoses/genética , Deficiência Intelectual/genética , Doença de Legg-Calve-Perthes/genética , Osteocondrodisplasias/genética , Fatores de Transcrição/genética , Adolescente , Adulto , Disostoses/diagnóstico por imagem , Disostoses/fisiopatologia , Humanos , Deficiência Intelectual/diagnóstico por imagem , Deficiência Intelectual/fisiopatologia , Doença de Legg-Calve-Perthes/diagnóstico por imagem , Doença de Legg-Calve-Perthes/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Osteocondrodisplasias/diagnóstico por imagem , Osteocondrodisplasias/fisiopatologia , Proteínas Repressoras , Deleção de Sequência , Adulto JovemRESUMO
Tricho-rhino-phalangeal syndrome (TRPS) is an autosomal-dominant disease characterized by sparse and slow-growing scalp hair and craniofacial and skeletal abnormalities. We report here the case of two girls and their father who had TRPS type 1 and received a diagnosis of a new mutation of TRPS1 based on their clinical symptoms. Moreover, histological studies on skin samples obtained from one of the patients showed enhanced signal transducers and activator of transcription (STAT) 3 expression in the outer root sheath. However, TRPS1 protein expression was not reduced in the patient's follicles. These findings indicate that truncated TRPS1 protein from the mutant allele may be stably expressed in the patient's follicles and that enhanced STAT3 expression may be involved in the development of sparse and thin scalp hair in TRPS.