Expert Reviewed By: Dr. Brandon Colby MD
Disproportionate short stature is a complex and heterogeneous condition, often associated with skeletal dysplasia and genetic syndromes such as Noonan-like facies. Understanding the genetic basis of this disorder is crucial for accurate diagnosis, appropriate management, and timely intervention. In recent years, advances in genetic testing have shed light on the underlying genetic causes of disproportionate short stature, providing valuable insights for patients and healthcare professionals.
Understanding Disproportionate Short Stature
Disproportionate short stature is characterized by an uneven growth pattern, resulting in a shorter-than-average height and disproportion between the limbs and trunk. This condition can be caused by various genetic factors, including mutations in specific genes and chromosomal abnormalities. Recent studies have identified several genetic variants associated with disproportionate short stature, highlighting the complexity and diversity of this disorder.
SAT-283 A Mutation In Ccdc53 Affects Pth1r Trafficking And Causes Disproportionate Short Stature With Noonan-like Facies
This study identified a de novo dominant mutation in the CCDC53 gene, which impairs interaction with WASH1 and affects PTH1R endocytic trafficking. This genetic variant is responsible for causing disproportionate short stature and Noonan-like facies, a syndrome characterized by facial features similar to those seen in Noonan syndrome.
SUN-LB008 Clinical Phenotype and Genotype Analysis of Short Stature Patients with Skeletal Dysplasia
This research analyzed the phenotype spectrum and genetic causes of skeletal-related short stature in Chinese patients. The study identified 19 variants in 5 genes, emphasizing the high heterogeneity of phenotypes associated with disproportionate short stature.
RAB33B and PCNT variants in two Pakistani families with skeletal dysplasia and short stature
This study investigated the genetic causes of skeletal dysplasia and short stature in two consanguineous Pakistani families. The researchers identified a known biallelic variant in the PCNT gene and a novel biallelic variant in the RAB33B gene, both of which contribute to the development of disproportionate short stature.
Genetic syndromes and skeletal dysplasia associated with short stature – A case series
This case series presented 25 patients with short stature, identifying genetic causes in 20 of them. The study highlighted common genetic syndromes like Noonan and Kabuki syndromes, as well as skeletal dysplasias like achondroplasia and epiphyseal dysplasia, which can result in disproportionate short stature.
Genetic Testing for Disproportionate Short Stature
Given the complex genetic landscape of disproportionate short stature, genetic testing plays a vital role in the accurate diagnosis and management of this condition. By identifying the specific genetic variants responsible for the disorder, healthcare professionals can provide personalized care and targeted interventions for patients.
Diagnostic Tool
Genetic testing can be used as a diagnostic tool to confirm the presence of a specific genetic variant or chromosomal abnormality associated with disproportionate short stature. This information can help healthcare professionals differentiate between various genetic syndromes and skeletal dysplasias, leading to more accurate diagnoses and tailored treatment plans.
Carrier Screening
For individuals with a family history of disproportionate short stature or related conditions, genetic testing can be used as a carrier screening tool. This allows prospective parents to determine their risk of passing on a genetic variant to their children, enabling them to make informed decisions about family planning and prenatal care.
Prognostic and Therapeutic Implications
By identifying the specific genetic cause of disproportionate short stature, healthcare professionals can better predict the potential severity and progression of the condition. This information can also guide the development of targeted therapies and interventions, ultimately improving the quality of life for patients with this disorder.
Conclusion
Disproportionate short stature is a complex and heterogeneous condition with diverse genetic causes. Advances in genetic testing have significantly improved our understanding of this disorder, allowing for more accurate diagnoses and personalized care. As research continues to uncover the genetic basis of disproportionate short stature, patients and healthcare professionals can look forward to a future of targeted therapies and improved outcomes.
About The Expert Reviewer
Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of and the author of Outsmart Your Genes.
Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (ACMG), an Associate of the American College of Preventive Medicine (ACPM), and a member of the National Society of Genetic Counselors (NSGC)