People with extremely short height often have genetic mutations: Ganga Ram Hospital study

Inherited genetic factors are largely responsible for normal variation in adult height, but those of extreme short stature often have mutations, according to a study conducted by researchers at the Sir Ganga Ram Hospital in Delhi.

Genetics plays an important part in determining an individual's height and the study has asserted the importance of a good clinical examination to enable the correct diagnosis of proportionate short stature, it said.

The study conducted at Institute of Genetics and Genomics, SGRH, between January 1, 2017 and October 31, 2018 involved 455 individuals aged between 10 months and 16 years.

A clinical profile assessment enabled diagnosis in 65% of the patients with proportionate short stature, according to the study.

"In this study, we tried to find and present the genetic spectrum of patients who were referred to our genetic clinic. Genetics plays an important part in determining an individual's height.

"Although there are many monogenic disorders (inherited disease controlled by fault in a single gene) that lead to perturbations in growth and result in short stature, this study asserts the importance of a good clinical examination to enable correct diagnosis," said Dr. Ratna Dua Puri, Chairperson, Institute of Medical Genetics and Genomics, SGRH.

"We wanted to reiterate that amongst the armamentarium of genetic tests available, a clinical profile assessment enables a diagnosis in 65 percent patients with proportionate short stature. Additionally, the tests to be offered would depend on the clinical profile," she said.

Normal variation in adult height is largely due to inherited genetic factors. But, by contrast, at the extreme of short stature, patients often have mutations in a single gene, resulting in huge effects on the height, the researchers said.

Of the 229 patients diagnosed on the basis of preliminary history, examination and investigations, 216 had Down's syndrome – a genetic disorder associated with physical growth delays.

Of the 226 patients who required detailed phenotyping and genetic testing, 142 (63%) had proportionate short stature (upper and lower body are equally short, abnormally). Of these, 93 had recognizable genetic syndromes such as Turner Syndrome (one of the X chromosomes is missing or partially missing), William Syndrome (rare genetic disorder that causes developmental and learning disabilities) and RASopathies (a group of rare genetic conditions), etc, it said. 

The rest of the children (84) had disproportionate short stature (either upper or lower part of the body is short), of which 38 had Lysosomal Storage Disorder (metabolic disorders which occur due to the lack of enzymes in the cell which leads to the accumulation of macromolecules). Thirty-seven children had Skeletal Dysplasias (shortening in the bones of the legs and arms).

"Through this study, we have attempted to represent the genetic spectrum of disorders in children with short stature and the appropriate testing indications. This becomes more relevant with the increasing ability of the tests and decreasing costs. "Achieving a definitive diagnosis can help to guide prognosis, provide treatment and genetic counseling to the families. Along with genetic tests, a good clinical examination of the child is very essential," Puri said.