BackgroundSilver–Russell syndrome (SRS) is characterised by intrauterine growth restriction, poor postnatal growth, relative macrocephaly, triangular face and asymmetry. Maternal uniparental disomy (mUPD) of chromosome 7 and hypomethylation of the imprinting control region (ICR) 1 on chromosome 11p15 are found in 5–10% and up to 60% of patients with SRS, respectively. As many features are non-specific, diagnosis of SRS remains difficult. Studies of patients in whom the molecular diagnosis is confirmed therefore provide valuable clinical information on the condition.MethodsA detailed, prospective study of 64 patients with mUPD7 (n=20) or ICR1 hypomethylation (n=44) was undertaken.Results and conclusionsThe considerable overlap in clinical phenotype makes it difficult to distinguish these two molecular subgroups reliably. ICR1 hypomethylation was more likely to be scored as ‘classical’ SRS. Asymmetry, fifth finger clinodactyly and congenital anomalies were more commonly seen with ICR1 hypomethylation, whereas learning difficulties and referral for speech therapy were more likely with mUPD7. Myoclonus-dystonia has been reported previously in one mUPD7 patient. The authors report mild movement disorders in three further cases. No correlation was found between clinical severity and level of ICR1 hypomethylation. Use of assisted reproductive technology in association with ICR1 hypomethylation seems increased compared with the general population. ICR1 hypomethylation was also observed in affected siblings, although recurrence risk remains low in the majority of cases. Overall, a wide range of severity was observed, particularly with ICR1 hypomethylation. A low threshold for investigation of patients with features suggestive, but not typical, of SRS is therefore recommended.

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Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes, caused by a mutation in the mitochondrial DNA (mtDNA) which impairs mitochondrial function by decreasing the e ciency of the Leucine Transfer ribonucleic acid (tRNA) in adding amino acids to developing proteins. MIDD has a prevalence of 0.5-3% among diabetic population but almost always misdiagnosed and managed as either Type 1 or Type 2 diabetes mellitus, which adversely impacts their long term outcome. So it is important to differentiate these cases early enough and to institute correct treatment. We report on 3 cases of MIDD which was con rmed by genetic testing and ve of their rst degree relatives with similar clinical presentation. A heteroplasmic missense mutation in the MT-TL1 gene (chrm: 3243A > G mitochondrial DNA) was detected in all three patients but genetic con rmation was not possible in their relatives for want of patient consent for genetic study. To our knowledge, this is the largest series of MIDD reported from India.

Maternally inherited diabetes and deafness (MIDD) is a rare form of diabetes, caused by a mutation in the mitochondrial DNA (mtDNA) which impairs mitochondrial function by decreasing the efficiency of the Leucine Transfer ribonucleic acid (tRNA) in adding amino acids to developing proteins. MIDD has a prevalence of 0.5–3% among diabetic population but almost always misdiagnosed and managed as either Type 1 or Type 2 diabetes mellitus, which adversely impacts their long term outcome. So it is important to differentiate these cases early enough and to institute correct treatment. We report on 3 cases of MIDD which was confirmed by genetic testing and five of their first degree relatives with similar clinical presentation. A heteroplasmic missense mutation in the MT-TL1 gene (chrm: 3243A > G mitochondrial DNA) was detected in all three patients but genetic confirmation was not possible in their relatives for want of patient consent for genetic study. To our knowledge, this is the largest series of MIDD reported from India.

INTRODUCTION: Diabetic foot ulcers (DFU) are a serious complication of diabetes mellitus that can have significant medical and socioeconomic impact as well as increase in mortality rates. Healing of ischemic or neuro ischemic foot ulcers is most challenging as conventional therapies often fail to achieve adequate vascularity. Ulcers of the heel area can be very severe and strenuous to treat and can eventually end up in the amputation of the limb due to poor vascularity. So optimization of therapies to improve vascularity should be a major objective in successfully treating such cases. CASE PRESENTATION: Here we report two cases of chronic non-healing ischemic ulcers of the heel area of the foot. Patients approached us after the conventional medical treatments had failed to achieve healing. We treated them with a cocktail (Diabcare protocol) that we formulated using existing medications along with appropriate wound care and antibiotics. Diabcare protocol comprises plaque regression agents (statins), antiplatelet drugs (Aspirin), novel oral anticoagulant (Rivaroxaban) and vasoactive agents [PDE3 inhibitor (Cilostazol) and PDE5 inhibitor (Tadalafil)]. On Serial measurements, ulcers showed progressive healing and wound contraction. Vascularity improved significantly and fresh granulation appeared within days to weeks of initiation of therapy. Ulcers healed completely, with spontaneous epithelialization in the first case and after SSG in the second case, within a mean period of three months. CONCLUSION The ‘Diabcare protocol’ is found to be effective in healing difficult-to-heal ischemic foot ulcers where conventional treatment fails.