RESUMO
Tricho-rhino-phalangeal syndrome (TRPS) is a rare malformation syndrome characterized by distinctive facial, ectodermal, and skeletal features. TRPS is divided into TRPS type I/III caused by pathogenic variants in TRPS1 and TRPS type II caused by contiguous gene deletions also spanning EXT1 and RAD21. Due to its rarity, knowledge of the clinical course of TRPS remains limited. Therefore, we collected and characterized a case series of 15 TRPS type I patients (median age at diagnosis 15 [interquartile range: 10-18] years, 11 females [73%]) seen at Aarhus University Hospital, Denmark, with a median follow-up period of 10 years. We estimated a minimum point prevalence of 0.5 in 100,000 (95% CI: 0.3-0.8 per 100,000) persons. Common craniofacial features included fine and sparse hair with a high anterior hairline, eyebrows with lateral thinning and a thicker medial part, prominent ears, a bulbous nose tip with small nasal alae, a low-hanging, and often wide columella, and a long philtrum with a thin upper vermillion. Specific skeletal features included short stature and deviating and short fingers with cone-shaped epiphyses and shortened metacarpals on radiographs. The most significant morbidity of the cohort was joint complaints, which were reported by all patients, often already before the TRPS diagnosis was established. We identified ten different TRPS1 variants including both frameshift/nonsense, missense, and splice-site variants, including seven variants not previously reported in the literature. In accordance with previous literature, no genotype-phenotype correlation was identified. The clinical trajectories were heterogeneous involving pediatrics, dermatology, orthopedic surgery, clinical genetics, and/or odontology, emphasizing that close multidisciplinary collaboration is essential for early diagnosis of TRPS and to ensure proper and timely patient care and counseling.
Assuntos
Proteínas de Ligação a DNA , Síndrome de Langer-Giedion , Proteínas Repressoras , Fatores de Transcrição , Adolescente , Criança , Feminino , Humanos , Masculino , Proteínas de Ligação a DNA/genética , Dedos/anormalidades , Doenças do Cabelo , Síndrome de Langer-Giedion/genética , Síndrome de Langer-Giedion/patologia , Nariz/anormalidades , Fenótipo , Proteínas Repressoras/genética , Fatores de Transcrição/genéticaAssuntos
Transtornos Cromossômicos/diagnóstico , DNA/genética , Adulto , Amniocentese , Aneuploidia , Gonadotropina Coriônica Humana Subunidade beta/sangue , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 18/genética , DNA/sangue , Feminino , Humanos , Medição da Translucência Nucal , Fragmentos de Peptídeos/sangue , Reação em Cadeia da Polimerase , Gravidez , Primeiro Trimestre da Gravidez , Gravidez de Alto Risco , Proteína Plasmática A Associada à Gravidez/metabolismo , Diagnóstico Pré-NatalRESUMO
Hydatidiform moles (HMs) are abnormal human pregnancies with vesicular chorionic villi, imposing two clinical challenges; miscarriage and a risk of gestational trophoblastic neoplasia (GTN). The parental type of most HMs are either diandric diploid (PP) or diandric triploid (PPM). We consecutively collected 154 triploid or near-triploid samples from conceptuses with vesicular chorionic villi. We used analysis of DNA markers and/or methylation sensitive-MLPA and collected data from registries and patients records. We performed whole genome SNP analysis of one case of twinning (PP+PM).In all 154 triploids or near-triploids we found two different paternal contributions to the genome (P1P2M). The ratios between the sex chromosomal constitutions XXX, XXY, and XYY were 5.7: 6.9: 1.0. No cases of GTN were observed. Our results corroborate that all triploid human conceptuses with vesicular chorionic villi have the parental type P1P2M. The sex chromosomal ratios suggest approximately equal frequencies of meiosis I and meiosis II errors with selection against the XYY conceptuses or a combination of dispermy, non-disjunction in meiosis I and meiosis II and selection against XYY conceptuses. Although single cases of GTN after a triploid HM have been reported, the results of this study combined with data from previous prospective studies estimate the risk of GTN after a triploid mole to 0% (95% CI: 0-1,4%).
Assuntos
Vilosidades Coriônicas/metabolismo , Mola Hidatiforme/genética , Aberrações dos Cromossomos Sexuais , Triploidia , Diploide , Feminino , Genoma Humano/genética , Genótipo , Humanos , Cariótipo , Cariotipagem , Masculino , Modelos Genéticos , GravidezRESUMO
The aim of this study was to examine the value of testing for a 22q11 microdeletion in fetuses with nuchal translucency (NT) above the 99th percentile (>3.5 mm). A 22q11 microdeletion results in the development of 22q11 deletion syndrome, a spectrum of disorders also known as DiGeorge/Velocardiofacial syndrome. A total of 146 pregnancies met the inclusion criteria of NT >3.5 mm between 11+2 and 13+6 weeks' gestation, no structural malformation and normal karyotype. Chorionic villi samples were tested with either multiplex ligation-dependent probe amplification (MLPA) or fluorescent in situ hybridization (FISH) analysis for 22q11 microdeletion. None were diagnosed with the microdeletion. The estimated prevalence of 22q11 microdeletion in these otherwise normal fetuses with increased NT is below 2.7%.
