A case of Coffin-Siris syndrome type 1 due to 6q25.3 deletion / 中华神经科杂志

Clinical data and genetic mutation characteristics of a patient with Coffin-Siris syndrome by 6q25.3 deletion were summarized. The child was a 7-year and 6-month old girl who had feeding difficulties, repeated infection, language and motor retardation, low intelligence, laryngeal cartilage dysplasia, thick eyebrows, sparse teeth, hairy back, hyperactivity and aggressive behavior, seizures and ataxia. There was no abnormality in chromosomal karyotype analysis by proband; genomic copy number variant sequencing (CNV-seq) indicated approximately 4.27 Mb heterozygous deletion in chromosome 6q25.3 region, with 17 genes including ARID1B gene, father maternal CNV-seq showing no abnormalities. Trio-whole-exome sequencing showed the proband missed all exons 1-20 of the ARID1B gene, with wild-type parents. The proband had severe clinical symptoms and haplodose insufficiency which was the genetic etiology.

Genotype and phenotype analysis of Coffin-Siris syndrome type 6 caused by novel variant of ARID2: one case report and literature review / 中华内分泌代谢杂志

Objective:To improve understanding of autosomal dominant Coffin-Siris syndrome(CSS) caused by ARID2 variant via analyzing the clinical manifestations and genetic characteristics of this rare disease. Methods:Whole-exome sequencing was performed in a patient with CSS and her parents in Children′s Hospital of Chongqing Medical University, and genotype and phenotype were further analyzed.Results:The 2-month-old girl was admitted to hospital due to repeated vomiting for more than a month and one-time vaginal bleeding. She presented with severe malnutrition, special facial features, premature development of bilateral breasts, hymen protrusion, and vaginal bleeding. Gene sequencing revealed a de novo heterozygous frameshift mutation(c.1919delC, p. P640Lfs*7) in ARID2 gene, and no variant identified with her parents. It has been reported that the clinical manifestations of CSS caused by ARID2 variant are heterogeneous varing, mainly characterized by growth retardation, mental retardation, and feeding difficulties, accompanied by skeletal deformities, behavioral abnormalities, and visual impairment. Endocrine abnormalities are seldomly reported.Conclusion:For patients presenting growth retardation, special facial features, feeding difficulties, and unexplained vaginal bleeding, rare genetic syndrome should be considered and genetic testing be carried out. This is a novel variant(c.1919delC, p.P640Lfs*7) in ARID2.

Síndrome de Coffin-Siris / Coffin­Siris syndrome

El presente estudio describe un caso de un niño de 6 años 9 meses de edad, atendido en el Centro de De-sarrollo Infantil de la Universidad de Cuenca (CEDIUC), con las características del Síndrome de Coffin ­Siris. El cariotipo 46xy, inv9 (p12q13), determinó por rasgos clíni-cos, el diagnóstico de Síndrome de Coffin ­Siris.Niño producto de cuarta gesta; antecedentes prena-tales: amenaza de aborto; antecedentes natales: nace a las 38.4 semanas de gestación con un diagnóstico de distrés respiratorio, por lo cual estuvo internado durante 15 días en la Unidad de Cuidados intensivos de la clínica Humanitaria; antecedentes post-natales: presentó retraso global en el desarrollo, además de otras afec-taciones como cardiopatía congénita, comunicación interventricular. Recibe tratamiento en varios Centros.El síndrome de Coffin-Siris es una enfermedad genética rara, con baja incidencia por lo que es poco estudiada, caracterizada por retardo mental, retraso en el desarro-llo psicomotor, facies toscas, pelo ralo e hipoplasia de la uña del quinto dedo.Se realizó una exhaustiva revisión bibliográfica, encon-trándose que el síndrome de Coffin-Siris es una enfer-medad genética poco frecuente; existen alrededor de 10 casos publicados en Latinoamérica; la etiología aún está en controversia, no ha podido definirse su localización cromosómica, pero algunos autores han plantea-do una posible herencia autosómica recesiva.

This study describes a case of a 6-years and 9-months-old child, who was attended at the Child Develop-ment Center of the University of Cuenca (CEDIUC), with the characteristics of the Coffin-Syndrome. The karyoty-pe 46xy, inv9 (p12q13), determined by clinical features the diagnosis of Coffin-Syndrome.Child product of the fourth pregnancy, prenatal history: threatened abortion; natal history: he born at 38.4 wee-ks of gestation with a diagnosis of respiratory distress, for this reason he was hospitalized for 15 days in the In-tensive Care unit of the Humanitarian clinic; post-natal history: he presented global developmental delay, in addition to other affections such as congenital heart di-sease and ventricular septal defect. He receives treat-ment in several centers.The Coffin-Siris syndrome is a rare genetic disease, with a low incidence and for this reason it is not studied enou-gh, it is characterized by mental retardation, delayed psychomotor development, coarse facies, thinning hair and hypoplasia of the fifth finger nail.A comprehensive bibliographic review was performed, and Coffin-Siris syndrome is a rare genetic disease with about 10 cases published in Latin America; the etiolo-gy is still controversial, its chromosomal location has not been defined, but some authors have raised a possible autosomal recessive inheritance.