ABSTRACT
ã We report on an infant with Opitz trigonocephaly C syndrome (OTCS), who also had manifestations of ciliopathy, including short ribs (non-asphyxiating), trident acetabular roofs, postaxial polydactyly cone-shaped epiphyses, and dysplasia of the renal, hepatic and pancreatic tissues. To investigate the molecular cause, we used an exome sequencing strategy followed by Sanger sequencing. Two rare variants, both predicted to result in loss of functional protein, were identified in the IFT140 gene; a substitution at the splice donor site of exon 24 (c.723 + 1 G > T) and a 17 bp deletion, impacting the first coding exon (c.-11_6del). The variants were confirmed as being biallelic using Sanger sequencing, showing that the splice variant was inherited from the propositus mother and the deletion from the father. To date, Mainzer-Saldino syndrome, Jeune syndrome, and a form of nonsyndromic retinal dystrophy, have been identified as ciliopathies caused by IFT140 mutations. We provide the first description of an OTCS phenotype that appears to result from IFT140 mutations. The presentation of this patient is consistent with previous reports showing that OTCS already exhibited skeleletal and nonskeletal features of a ciliopathy.
Subject(s)
Carrier Proteins/genetics , Ciliopathies/genetics , Craniosynostoses/genetics , Genetic Predisposition to Disease , Intellectual Disability/genetics , Ciliopathies/diagnosis , Ciliopathies/physiopathology , Craniosynostoses/diagnosis , Craniosynostoses/physiopathology , Exome/genetics , Female , Heterozygote , High-Throughput Nucleotide Sequencing , Humans , Intellectual Disability/diagnosis , Intellectual Disability/physiopathology , Male , Pedigree , RNA Splice Sites/genetics , Sequence Deletion/geneticsABSTRACT
De 200 casos de tumores primarios del sistema nervioso central, 14 (7 por ciento) resultaron tumores de células germinales, histológicamente 11 de ellos fueron germinomas, dos teratomas inmaduros con áreas de coroacarcinoma y tumor de senos endodérmicos (TI-C-TSE) y un teratoma maduro. Las manifestaciones clínicas iniciales fueron de tipo neuronal y endocrinológicas: hidrocefalia (57 por ciento) de campo visual (50 por ciento), ataxia y signos piramidales (43 por ciento), convulsiones (43 por ciento), paresias de pares craneános (36 por ciento), signo de Parinaud (21 por ciento), atrofia óptica 14 por ciento; hiperprolactinemia (43 por ciento), talla baja (43 por ciento), diabetes insípida (43 por ciento), pubertad precoz, hipotiroidismo e insuficiencia adrenal (7 por ciento) respectivamente. Las tomografías computarizadas de cráneo (TCC) evidenciaron el proceso tumoral en el 100 por ciento de los casos, contrastando con las radiografías simples de cráneo que sólo lo mostraron en el 36 por ciento de los casos. El tratamiento en todos fue cirugía y radioterapia sólo uno recibió quimioterapia, el TI-C.TSE con metástasis pulmonar. Concluimos que los germinomas deberán recibir radioterapia como tratamiento inicial. Es imprescindible la TCC, la búsqueda de células exfoliativas en líquido cefalorraquídeo y marcadores tumorales para el diagnóstico, así como las determinaciones hormonales necesarias
