Insights into genotype-phenotype correlations in spinal muscular atrophy: a retrospective study of 103 patients.

Spinal muscular atrophy (SMA) is an autosomal recessive disorder associated with homozygous deletion of the survival motor neuron 1 gene (SMN1). Its centromeric copy gene, SMN2, is the major modifying factor. However, the genotype-phenotype correlation is incomplete and is therefore not useful in clinical practice. We studied a cohort of 103 patients in order to refine this correlation. In addition to standard disease severity data, we collected three additional criteria: age at death; brainstem involvement; and loss of ambulation. Gene dosage analysis was conducted by multiplex ligation-dependent probe amplification (MLPA). SMN2 copynumber was highly correlated with survival duration in SMA type I and ambulation conservation or loss in type III. Among SMA severity groups, it was not significantly different in cases with brainstem involvement. Although the SMN2 copynumber could provide prognostic indications, clinical discrepancies still exist among patients, suggesting the existence of unidentified modifying factors.

Biomarkers of neuroendocrine tumors.

Neuroendocrine tumors (NET) are rare heterogenous tumors which prevalence is increasing. Their features vary by anatomical location, functionality and hormonal production. Their management needs a multidisciplinary approach. Functional tumors develop characteristic clinical syndromes in contrast to non-functional tumors that are diagnosed fortuitously or at advanced stage. NET can secrete many specific and general biomarkers. CgA is the most sensitive general marker. Its value should be interpreted along with the renal function and the gastrin level. Some new biomarkers such as NTproBNP, proGRP and NET gene transcripts have been identified. The latter are not yet routine in clinical practice. We present In this review biological biomarkers involved in NET with a focus on the assays and their use in clinical practice.

Is hormonal activation during exercise useful for risk stratification in patients with moderate congestive heart failure?

BACKGROUND: We previously demonstrated that A-type natriuretic peptide (ANP) at peak exercise was an independent predictor of cardiac survival. No data are available concerning the predictive value of B-type natriuretic peptide (BNP) at peak exercise. METHODS: One hundred and fifty consecutive stable patients with moderate congestive heart failure (CHF) underwent echocardiography and a cardiopulmonary exercise test. Blood samples were drawn at rest and at peak exercise for the determination of plasma levels of ANP, BNP, and norepinephrine. RESULTS: Exercise significantly increased plasma values of ANP, BNP, and norepinephrine. After a median follow-up period of 1171 days, there were 35 cardiac related deaths. Mortality rates at 1 and 2 years were 4% and 8%, respectively. Independent predictors of cardiac survival were percent of maximal predicted oxygen consumption (RR = 4.8 [2.1-11], P =.002), BNP at rest (RR = 2.5 [1.2-5.6], P =.01), and left atrial diameter (RR = 2.8 [1.2-6.5], P =.02). CONCLUSIONS: In patients with stable, moderate CHF, plasma levels of ANP, BNP, and norepinephrine measured at peak exercise did not improve risk stratification. However, in addition to percent of maximal predicted oxygen consumption and left atrial diameter, plasma level of BNP at rest was an independent predictor of survival in CHF patients with low risk of cardiac events.

[Biological diagnosis of pheochromocytoma in 2014]. / Le diagnostic biologique de phéochromocytome en 2014.

Pheochromocytomas and/or paragangliomas are rare, heterogeneous tumors of the chromaffin cells. Thirty percent of the patients presented with these diseases in a hereditary context. The biological diagnosis relies on the identification of excessive secretion of the metanephrines which are more sensitive and specific than those of catecholamines. The published recommendations give the opportunity to choose between the metanephrines in sera or urines. The concentrations of the free plasmatic metanephrines reflect the ongoing production of tumor. They are little sensitive to the renal failure. The gold standard method to measure the free metaphrines in plasma is the LC-MS/MS chromatography. This is the technical event that we use since 2008, and we relate our experience.

Local-regional recurrence of sporadic or syndromic abdominal extra-adrenal paraganglioma: incidence, characteristics, and outcome.

BACKGROUND: Operative excision of abdominal extra-adrenal paragangliomas (EAPs) does not preclude the late development of local-regional recurrence. We describe the incidence, characteristics, and outcome of this rarely reported feature. METHODS: Retrospective analysis of local-regional recurrence that occurred during follow-up of 51 consecutive patients operated for a sporadic (n = 26) or hereditary (n = 25) EAP. RESULTS: Seven patients with a sporadic or syndromic EAP (n = 4: von Hippel-Lindau syndrome and SDHB, SDHC, and SDHD gene mutations) underwent reoperation for a local-regional recurrence after a median time of 46 months (interquartile range [IQR], 16-100). The Kaplan-Meier estimated incidence of local-regional recurrence (+/- standard error of the mean) reached 15% +/- 7% at 5 years and 23% +/- 9% after 10 years. Recurrent EAPs were all secreting and 38% provoked clinical symptoms. New lesions were smaller than the primary EAP (P = .01) and more often associated with lymph node metastases (43% vs 4%, P = .01). Operative excision seemed complete in 5 patients. Clinical remission was maintained in 4 patients after a median follow-up of 57 months (IQR, 22-102). CONCLUSION: Local-regional recurrence of sporadic and syndromic EAPs is frequent and may be delayed beyond 10 years, requiring lifelong follow-up after the initial operation. When technically feasible, operative excision can lead to prolonged remission.