Clinical and Genetic Profile of Children With Short Stature Presenting to a Genetic Clinic in Northern India

Objective: To define the spectrum of genetic disorders in patients with short stature visiting the genetic out-patient department in a tertiary care hospital. Methods: A chart review was done for 455 individuals (10 months-16 yrs) with short stature, who were evaluated at the genetic clinic from 1 January, 2017 upto 31 October, 2018. 226 patients who needed detailed evaluation, the spectrum of genetic diagnosis is presented. Results: Proportionate short stature was identified in 63% individuals (n=142) of which 93 (65%) were recognizable syndromes such as Turner syndrome, and William syndrome, and RASopathies. In clinically undefined syndromes (39, 27%), a diagnosis could be made by karyotype (n=3/10), chromosomal microarray (6/12) and exome sequencing (1/6). In the 84 children in the disproportionate short stature group (37%), lysosomal storage disorders (LSDs) (45%, n=38) were identified by enzyme analysis in 86.8% and skeletal dysplasias (44%, n=37) identified by skeletal survey in 89% cases. Conclusions: In undefined syndromic short stature, chromosomal microarray may be the first investigation of choice if phenotyping is not suggestive of a specific genetic syndrome. Exome sequencing can be useful in identifying newer genes among idiopathic and familial short stature cohorts.

The Medical Termination of Pregnancy (Amendment) Act, 2021: A step towards liberation

Reform of the abortion laws in favour of the well-being of pregnant women is one aspect of the removal of gender discrimination. The Medical Termination of Pregnancy Act (MTP Act) 1971, was a breakthrough legislation in this regard, as it reduced the number of unsafe illegal abortions. With advancements in ultrasonography and genetic technologies, many foetal malformations and genetic disorders were being diagnosed after 20 weeks of gestation. The fact that termination of pregnancy was not legally permitted beyond 20 weeks of gestation caused great distress to such women, and highlighted the need to increase the upper limit of termination of pregnancy. Concurrently, there has been greater awareness around the world on the rights of women to take decisions regarding their own bodies. The MTP Bill, 2020, has come as a breath of fresh air extending the term limit for legal abortions to 24 weeks for certain categories of women, and removing the limit for abortion in the presence of a significant foetal abnormality. The amendments were recently approved by Parliament and the President of India, and have become law as of March 25, 2021. This paper presents the amendments made and their implications for obstetric, ultrasonographic and foetal medical practice. It also presents a critique of the various Acts and suggests further amendments that would enhance the value of the Act.

Prevalence of familial hypercholesterolemia in premature coronary artery disease patients admitted to a tertiary care hospital in North India

Aims The prevalence of premature coronary artery disease (CAD) in India is two to three times more than other ethnic groups. Untreated heterozygous familial hypercholesterolemia (FH) is one of the important causes for premature CAD. As the age advances, these patients without treatment have 100 times increased risk of cardiovascular (CV) mortality resulting from myocardial infarction (MI). Recent evidence suggests that one in 250 individuals may be affected by FH (nearly 40 million people globally). It is indicated that the true global prevalence of FH is underestimated. The true prevalence of FH in India remains unknown. Methods A total of 635 patients with premature CAD were assessed for FH using the Dutch Lipid Clinical Network (DLCN) criteria. Based on scores, patients were diagnosed as definite, probable, possible, or no FH. Other CV risk factors known to cause CAD such as smoking, diabetes mellitus, and hypertension were also recorded. Results Of total 635 patients, 25 (4%) were diagnosed as definite, 70 (11%) as probable, 238 (37%) as possible, and 302 (48%) without FH, suggesting the prevalence of potential (definite + probable) FH of about 15% in the North Indian population. FH is more common in younger patients, and they have lesser incidence of common CV risk factors such as diabetes, hypertension, and smoking than the younger MI patients without FH (26.32% vs.42.59%; 17.89% vs.29.44%; 22.11% vs.40.74%). Conclusion FH prevalence is high among patients with premature CAD admitted to a cardiac unit. To detect patients with FH, routine screening with simple criteria such as family history of premature CAD combined with hypercholesterolemia, and a DLCN criteria score >5 may be effectively used.

Ethylmalonic Encephalopathy in an Indian Boy.

Background: Ethylmalonic encephalopathy is a rare inborn error of metabolism characterized by neurodevelopmental delay / regression, recurrent petechiae, orthostatic acrocyanosis, and chronic diarrhea. Case Characteristics: 4-year-old boy with developmental regression, chronic diarrhea, petechial spots and acrocyanosis. MRI brain showed T2W/FLAIR hyperintensities in bilateral caudate and putamen. Abnormal acyl-carnitine profile and metabolites on urinary GC-MS analysis suggested the diagnosis. Intervention: Sequencing of ETHE1 gene revealed mutations: c.488G>A and c.375+5G>T (novel). Message: EE is clinically-recognizable disorder with typical clinical features.