RESUMEN
Fanconi anaemia (FA) is a genetic disorder due to mutations in any of the 22 FANC genes (FANCA-FANCW) and has high phenotypic variation. Siblings may have similar clinical outcome because they share the same variants; however, such association has not been reported. We present the detailed phenotype and clinical course of 25 sibling sets with FA from two institutions. Haematological progression significantly correlated between siblings, which was confirmed in an additional 55 sibling pairs from the International Fanconi Anemia Registry. Constitutional abnormalities were not concordant, except for a moderate degree of concordance in kidney abnormalities and microcephaly.
Asunto(s)
Anemia de Fanconi , Riñón , Microcefalia , Sistema de Registros , Hermanos , Anemia de Fanconi/sangre , Anemia de Fanconi/genética , Anemia de Fanconi/inmunología , Femenino , Humanos , Riñón/anomalías , Riñón/inmunología , Riñón/metabolismo , Masculino , Microcefalia/genética , Microcefalia/inmunología , Microcefalia/metabolismo , Estudios RetrospectivosRESUMEN
BACKGROUND: Shwachman-Diamond Syndrome (SDS) is an autosomal recessive disorder characterized by bone marrow failure and exocrine pancreatic dysfunction. Heart failure has been described in patients with SDS. Circumferential strain (ε(cc)) is a measure of cardiac performance that may identify dysfunction when standard measures are normal. PROCEDURES: Patients with SDS were identified and the echocardiographic database queried. Cardiac anatomy and function were recorded, and ε(cc) was measured retrospectively. RESULTS: From 1995-2013, 27 patients with biallelic SBDS mutations confirming the diagnosis of SDS were identified at our institution: 14 had at least one echocardiogram available; 10 underwent HSCT, with echocardiograms available in nine. Ejection fraction (EF) was normal in all 14 patients evaluated; however, ε(cc) was decreased in 4/12 studies prior to HSCT. In two patients, ε(cc) was abnormal both before and after HSCT, in one, ε(cc) changed from normal to abnormal after HSCT, and in one, ε(cc) was normal after HSCT despite being abnormal prior. Echocardiogram reports were also available for six patients in the North American SDS registry, all with normal EF. CONCLUSIONS: While EF was normal in all patients with SDS, ε(cc) was abnormal in 33% prior to HSCT and 33% of those who had undergone HSCT. This suggests that SDS is associated with systolic dysfunction. Further studies are needed to define the incidence of dysfunction in this group and the progression to heart failure.
