RESUMEN
OBJECTIVE: To describe the clinical features, therapeutic interventions, and patient outcomes of gastrointestinal (GI) hemorrhage in individuals with a telomere biology disorder, including dyskeratosis congenita, Hoyeraal-Hreidarsson syndrome, Revesz syndrome, and Coats plus. STUDY DESIGN: Clinical Care Consortium for Telomere Associated Ailments members were invited to contribute data on individuals with telomere biology disorders at their institutions who experienced GI bleeding. Patient demographic, laboratory, imaging, procedural, and treatment information and outcomes were extracted from the medical record. RESULTS: Sixteen patients who experienced GI hemorrhage were identified at 11 centers. Among 14 patients who underwent genetic testing, 8 had mutations in TINF2, 4 had mutations in CTC1 or STN1, and 1 patient each had a mutation in TERC and RTEL1. Ten patients had a history of hematopoietic cell transplantation. The patients with Coats plus and those without Coats plus had similar clinical features and courses. Angiodysplasia of the stomach and/or small bowel was described in 8 of the 12 patients who underwent endoscopy; only 4 had esophageal varices. Various medical interventions were trialed. No single intervention was uniformly associated with cessation of bleeding, although 1 patient had a sustained response to treatment with bevacizumab. Recurrence was common, and the overall long-term outcome for affected patients was poor. CONCLUSIONS: GI bleeding in patients with telomere biology disorders is associated with significant morbidity and with vascular ectasias rather than varices.
Asunto(s)
Hemorragia Gastrointestinal/etiología , Telómero/genética , Adolescente , Adulto , Ataxia/complicaciones , Ataxia/genética , Enfermedades Óseas Metabólicas/complicaciones , Enfermedades Óseas Metabólicas/genética , Médula Ósea/anomalías , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/genética , Calcinosis/complicaciones , Calcinosis/genética , Quistes del Sistema Nervioso Central/complicaciones , Quistes del Sistema Nervioso Central/genética , Niño , Preescolar , Disqueratosis Congénita/complicaciones , Disqueratosis Congénita/genética , Femenino , Retardo del Crecimiento Fetal/genética , Hemorragia Gastrointestinal/genética , Humanos , Discapacidad Intelectual/complicaciones , Discapacidad Intelectual/genética , Leucoencefalopatías/complicaciones , Leucoencefalopatías/genética , Masculino , Microcefalia/complicaciones , Microcefalia/genética , Espasticidad Muscular/complicaciones , Espasticidad Muscular/genética , Mutación , Retina , Enfermedades de la Retina/complicaciones , Enfermedades de la Retina/genética , Convulsiones/complicaciones , Convulsiones/genética , Telómero/metabolismo , Telómero/patología , Adulto JovenRESUMEN
OBJECTIVES: To investigate the range of clinical presentations for Shwachman-Diamond syndrome (SDS) with the long-term goal of improving diagnosis. STUDY DESIGN: We reviewed the North American Shwachman-Diamond Syndrome Registry. Genetic reports of biallelic Shwachman-Bodian-Diamond syndrome mutations confirming the diagnosis of SDS were available for 37 patients. RESULTS: Neutropenia was the most common hematologic abnormality at presentation (30/37, 81%); however, only 51% (19/37) of patients presented with the classic combination of neutropenia and steatorrhea. Absence of pancreatic lipomatosis on ultrasound or computed tomography scan, normal fecal elastase levels, and normal skeletal survey do not rule out the diagnosis of SDS. SDS was diagnosed in 2 asymptomatic siblings of SDS probands. Twenty-four of 37 patients (65%) had congenital anomalies. CONCLUSION: Our cohort reveals a broad range of clinical presentation for SDS. Clues to the underlying diagnosis of SDS included cytopenias with a hypocellular marrow, congenital anomalies, family history, and myelodysplasia with clonal abnormalities frequently found in SDS. Reliance on classic clinical criteria for SDS would miss or delay diagnosis of a significant subset of patients with SDS.
Asunto(s)
Enfermedades de la Médula Ósea/diagnóstico , Insuficiencia Pancreática Exocrina/diagnóstico , Lipomatosis/diagnóstico , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , América del Norte , Sistema de Registros , Estudios Retrospectivos , Síndrome de Shwachman-DiamondRESUMEN
OBJECTIVE: To characterize the endocrine phenotype of patients with Shwachman-Diamond syndrome (SDS). STUDY DESIGN: Clinically indicated endocrine screening data from 43 patients with SDS or SDS-like presentation were analyzed according to sex, age, and genetic testing. In addition to 25 patients with biallelic Shwachman-Bodian-Diamond syndrome (SBDS) gene mutations, we evaluated 18 patients with cytopenias who were receiving pancreatic enzyme replacement but were without SBDS mutation. We performed a retrospective review of growth records and clinically indicated endocrine evaluations. RESULTS: Of patients with SBDS mutations, 2 had low stimulated growth hormone levels, 2 had mildly elevated thyrotropin levels, 5 had abnormal glucose levels, and 1 had an elevated follicle-stimulating hormone level (post transplantation). In contrast, 1 patient without SBDS mutations had postprandial hyperglycemia and 3 had mildly low free thyroxine levels without short stature. Endocrine abnormalities were identified in 19% of short patients and 26% of the whole group. Of patients with SBDS mutations, 56% had a height expressed in SD units from the mean for age and sex of <-1.8, in contrast to only 12% of patients without SBDS mutations (38% of the whole group). Body mass index z score was significantly greater in the group with SBDS mutations (P<.001). CONCLUSION: Although short stature was more common in patients with SBDS mutations, no consistent endocrine phenotype was observed in patients with SDS regardless of genetic testing.