RESUMEN
Human nude SCID is a rare autosomal recessive inborn error of immunity (IEI) characterized by congenital athymia, alopecia, and nail dystrophy. Few cases have been reported to date. However, the recent introduction of newborn screening for IEIs and high-throughput sequencing has led to the identification of novel and atypical cases. Moreover, immunological alterations have been recently described in patients carrying heterozygous mutations. The aim of this paper is to describe the extended phenotype associated with FOXN1 homozygous, compound heterozygous, or heterozygous mutations. We collected clinical and laboratory information of a cohort of 11 homozygous, 2 compound heterozygous, and 5 heterozygous patients with recurrent severe infections. All, except one heterozygous patient, had signs of CID or SCID. Nail dystrophy and alopecia, that represent the hallmarks of the syndrome, were not always present, while almost 50% of the patients developed Omenn syndrome. One patient with hypomorphic compound heterozygous mutations had a late-onset atypical phenotype. A SCID-like phenotype was observed in 4 heterozygous patients coming from the same family. A spectrum of clinical manifestations may be associated with different mutations. The severity of the clinical phenotype likely depends on the amount of residual activity of the gene product, as previously observed for other SCID-related genes. The severity of the manifestations in this heterozygous family may suggest a mechanism of negative dominance of the specific mutation or the presence of additional mutations in noncoding regions.
Asunto(s)
Factores de Transcripción Forkhead/genética , Heterocigoto , Homocigoto , Mutación , Fenotipo , Inmunodeficiencia Combinada Grave/diagnóstico , Inmunodeficiencia Combinada Grave/etiología , Línea Celular , Preescolar , Análisis Mutacional de ADN , Manejo de la Enfermedad , Femenino , Factores de Transcripción Forkhead/química , Estudios de Asociación Genética , Sitios Genéticos , Predisposición Genética a la Enfermedad , Trasplante de Células Madre Hematopoyéticas , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Modelos Moleculares , Conformación Molecular , Linaje , Inmunodeficiencia Combinada Grave/terapia , Relación Estructura-Actividad , Resultado del TratamientoRESUMEN
Pancreatoblastoma (PB) is a rare pancreatic neoplasm which arises when a group of pancreatic cells start to go through uncontrollable growth. The diagnosis of PB is challenging due to its vague symptoms. The initial diagnosis is made by imaging, afterwards the management is usually by resection of the tumor with or without chemotherapy which depends on the size and grade of the tumor. We report a case of a nine-year-old girl who was diagnosed with pancreotoblastoma and underwent complete resection with chemotherapy.
RESUMEN
Severe combined immunodeficiency (SCID) is an extremely rare disease caused by a disruption in the forkhead box N1 (FOXN1) gene, with an incidence of <1 per 1 000 000 live births. We report a boy aged 4 months who presented with a history of fever for 3 weeks and enlarged lymph nodes. The fever was associated with dry cough and runny nose. On physical examination, we noted oral thrush, generalised lymphadenopathy, nail dystrophy and alopecia. Flow cytometry of lymph node biopsy showed high-grade B-cell lymphoma. In addition, Epstein-Barr virus (EBV) infection was documented by PCR. The diagnosis of SCID was made by genetic testing, which revealed a homozygous variant of the FOXN1 gene. The variant was confirmed with Sanger sequencing. Management of EBV infection and lymphoma was initiated; unfortunately, the patient passed away on day 45 of hospitalisation.