RESUMEN
OBJECTIVES: To determine the diagnostic yield of next generation sequencing (NGS) in patients with moderate/severe/profound intellectual disability (ID) unexplained by conventional tests and to assess the impact of definitive diagnosis on the clinical management and genetic counselling of these families. METHODS: This was a ambi-directional study conducted at Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi. The study comprised 227 patients (prospective cohort - 126, retrospective cohort - 101) in whom NGS based tests were performed. RESULTS: The mean age of study cohort was 4.5 ± 4.4 y (2.5 mo to 37.3 y). The male: female ratio was 1.6:1. The overall diagnostic yield of NGS was 53.3% (121/227) with causative variants identified in 84 known ID genes. Autosomal recessive intellectual disability (ARID) (23.3%, 53/227) was the most common followed by autosomal dominant intellectual disability (ADID) (20.7%, 47/227) and X-linked intellectual disability (XLID) (9.2%, 21/227). The diagnostic yield was notably higher for ID plus associated condition group (55.6% vs. 20%) (p = 0.0075, Fisher's exact test) compared to isolated ID group. The impact of diagnosis on active or long-term management was observed in 17/121 (14%) and on reproductive outcomes in 26/121 (21.4%) families. CONCLUSIONS: There is paucity of data on molecular genetic spectrum of ID from India. The current study identifies extensive genetic heterogeneity and the impact of NGS in patients with ID unexplained by standard genetic tests. The study identified ARID as the most common cause of ID with additional implications for reproductive outcomes. It reiterates the importance of phenotype in genetic testing.
RESUMEN
Trisomy 18 or Edward syndrome is a chromosomal disorder due to the presence of an extra chromosome 18. We describe the phenotype of five fetuses at different gestational ages, each highlighting a different aspect of trisomy 18. The clinical spectrum included increased nuchal translucency, fetal hydrops, congenital malformations of the central nervous system, congenital heart disease, radial ray defects, and characteristic facial gestalt. We made a comparison of prenatal ultrasonography and the autopsy findings. The fetal autopsy defined the craniofacial and digit anomalies better compared with sonography. The facial features of tall forehead, hypoplastic nares, microstomia, micrognathia, low set abnormal ears along with clenched hands, and short hallux are typical for trisomy 18 and help in planning the targeted cytogenetic or molecular tests. The diagnosis was established by either fluorescence in situ hybridization or quantitative fluorescent polymerase chain reaction or chromosomal microarray in the patients. This communication emphasizes the importance of detailed assessment for craniofacial and limb anomalies on prenatal ultrasonography which can prompt an early evaluation for trisomy 18.
Asunto(s)
Trisomía , Ultrasonografía Prenatal , Femenino , Humanos , Hibridación Fluorescente in Situ , Fenotipo , Embarazo , Trisomía/diagnóstico , Trisomía/genética , Síndrome de la Trisomía 18/diagnóstico , Síndrome de la Trisomía 18/genéticaRESUMEN
Parasitic infections are the leading cause of hypereosinophilia in the paediatric population in tropical countries. We report an unusual case of Toxocara infection in an eight-year-old boy who presented with intermittent fever, hypereosinophilia complicated by massive pericardial effusion and a mycotic aneurysm. This child received treatment with four weeks of albendazole and steroids.
Asunto(s)
Aneurisma Infectado , Eosinofilia , Derrame Pericárdico , Toxocariasis , Albendazol/uso terapéutico , Aneurisma Infectado/diagnóstico , Aneurisma Infectado/tratamiento farmacológico , Aneurisma Infectado/etiología , Animales , Niño , Humanos , Masculino , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/tratamiento farmacológico , Derrame Pericárdico/etiología , Toxocariasis/complicaciones , Toxocariasis/diagnóstico , Toxocariasis/tratamiento farmacológicoRESUMEN
Hypophosphatemic rickets is one of the major causes of refractory rickets exhibiting genetic heterogeneity. Most cases are X-linked due to PHEX gene mutations. However recently, autosomal dominant (AD) forms have been described, due to mutations in FGF23. The authors present a 13-year-old girl who had hypophosphatemic rickets due to R179W mutation in FGF23 gene, being the first case in India with this mutation. She presented with bone pains, short stature and osteopenic bones, symptoms appearing after onset of menarche. This presentation is different from that seen in younger children with rickets. Burosumab, an anti-FGF23 antibody is an effective novel therapy for FGF23-related rickets but it is not available in India. High doses of calcitriol and phosphate were required to alleviate the symptoms and signs. The authors aim to alert pediatricians to keep in mind this treatable disorder to prevent diagnostic delays and improve treatment outcome.
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Raquitismo Hipofosfatémico Familiar , Factores de Crecimiento de Fibroblastos/genética , Raquitismo Hipofosfatémico , Adolescente , Análisis Mutacional de ADN , Raquitismo Hipofosfatémico Familiar/diagnóstico , Raquitismo Hipofosfatémico Familiar/tratamiento farmacológico , Raquitismo Hipofosfatémico Familiar/genética , Femenino , Factor-23 de Crecimiento de Fibroblastos , Humanos , India , Mutación , Fosfatos , Raquitismo Hipofosfatémico/diagnóstico , Raquitismo Hipofosfatémico/tratamiento farmacológico , Raquitismo Hipofosfatémico/genéticaAsunto(s)
Anoctaminas/genética , Predisposición Genética a la Enfermedad , Variación Genética , Osteogénesis Imperfecta/diagnóstico , Osteogénesis Imperfecta/genética , Fenotipo , Cráneo/anomalías , Adulto , Alelos , Biomarcadores , Densidad Ósea , Estudios de Asociación Genética , Heterocigoto , Humanos , India , Masculino , Mutación , Osteogénesis Imperfecta/metabolismo , Tomografía Computarizada por Rayos XAsunto(s)
Distrofias Retinianas/diagnóstico , alfa-Manosidosis/diagnóstico , alfa-Manosidosis/genética , Adulto , Alelos , Preescolar , Consanguinidad , Análisis Mutacional de ADN , Facies , Femenino , Angiografía con Fluoresceína , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Mutación , Linaje , Fenotipo , Distrofias Retinianas/etiología , Evaluación de Síntomas , alfa-Manosidasa/genética , alfa-Manosidasa/metabolismo , alfa-Manosidosis/complicacionesRESUMEN
Musculocontractural type of Ehlers-Danlos syndrome (MC-EDS) is a recently recognised connective tissue disorder. MC-EDS is caused by homozygous or compound heterozygous mutation in the carbohydrate sulfotransferase 14 (CHST14) gene on chromosome 15q15. Herein, we report a case of a 3-year-old boy with MC-EDS in whom a novel mutation in the CHST14 gene was discovered. Besides being the second report of this rare disorder from India, the child till 3 years has not had any bleeding tendency as described in the earlier reports of this disorder.