Objectives
HbS/β+ patients’ presence in Italy increased due to immigration; these patients are clinically heterogeneous, and specific guidelines are lacking. Our aim is to describe a cohort of HbS/β+ patients, with genotype‐phenotype correlation, in order to offer guidance for clinical management of such patients.
Methods
Retrospective cohort study of HbS/β+ patients among 15 AIEOP Centres.
Results
A total of 41 molecularly confirmed S/β+ patients were enrolled (1‐55 years, median 10.9) and classified on β+ mutation: IVS‐I‐110, IVS‐I‐6, promoter, and “others.” Prediagnostic events included VOC 16/41 (39%), ACS 6/41 (14.6%), sepsis 3/41 (3.7%), and avascular necrosis 3/41 (7,3%). Postdiagnostic events were VOC 22/41 (53.6% %), sepsis 4/41 (9.7%), ACS 4/41 (9.7%), avascular necrosis 3/41 (7.3%), aplastic crisis 2/41 (4.8%), stroke 1/41 (2.4%), ACS 1/41 (2.4%), and skin ulcerations 1/41 (2.4%). The IVS‐I‐110 group presented the lowest median age at first SCD‐related event (P = .02 vs promoter group) and the higher median number of severe events/year (0.26 events/patient/year) (P = .01 vs IVS‐I‐6 and promoter groups). Promoter group presented a specific skeletal phenotype. Treatment regimen applied was variable among the centers.
Conclusions
HbS/β+ is not always a mild disease. Patients with IVS‐I‐110 mutation could benefit from a standard of care like SS and S/β° patients. Standardization of treatment is needed.
We report the case of two siblings presenting with failure to thrive in early years, progressive microcephaly, moderate intellectual disability, developmental delay, ataxic gait and seizures with an identical EEG pattern, and minimal cerebellar atrophy. We ruled out the syndromic and metabolic causes of microcephaly and subsequently conducted a panel of genetic diagnostic tests, including the clinical exome sequencing which revealed compound heterozygous mutations in MED 17 gene in both patients. p.Glu16fs was found to be inherited from the mother and p.Gly253Arg from the father. This case along with review of the literature suggests that mutations in MED17 may define a phenotype characterized by progressive microcephaly, intellectual disability, seizures, cerebellar atrophy of variable degree, and ataxia. More cases are needed to define the phenotype-genotype correlation in MED17 mutations. However, basing on our findings, we recommend testing MED17 mutations in any patient presenting with two or more of the aforementioned signs and symptoms.
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