Kniest Dysplasia

Description

Kniest dysplasia is a rare genetic disorder characterized by abnormal bone growth, leading to short stature, disproportionate limbs, and joint limitations. It is a type of skeletal dysplasia, a group of disorders affecting bone development. This blog provides a comprehensive overview of Kniest dysplasia, covering its signs and symptoms, causes, diagnosis, management, and ways individuals with this condition can thrive.

Genes Involved

Kniest dysplasia is caused by mutations in specific genes involved in cartilage formation and bone development. Two primary genes are associated with this condition:

COMP (Cartilage Oligomeric Matrix Protein): Mutations in this gene are the most common cause of Kniest dysplasia.
RMRP (Ribonucleoprotein MRP): Mutations in this gene are rarer but can also lead to Kniest dysplasia.

Recognizing the Signs and Symptoms

Kniest dysplasia presents with a unique set of features, often noticeable at birth or within the first few years of life. Some of the most common signs and symptoms include:

Short stature: Individuals with Kniest dysplasia are significantly shorter than average.
Disproportionate limbs: Arms and legs are shorter compared to the torso.
Joint limitations: The knees, elbows, and hips may have limited range of motion.
Large head (macrocephaly): The head may be unusually large in proportion to the body.
Short neck: The neck may appear short and thick.
Barrel chest: The chest may be broad and rounded.
Bowing of the legs (genu varum): The legs may curve outward.
Waddling gait: Individuals may walk with a waddling motion.
Scoliosis: Spinal curvature may occur.
Breathing difficulties: Due to the narrow chest, breathing might be labored.
Hearing loss: Some individuals may experience hearing loss.
Intellectual disability: While most individuals have normal intelligence, some may experience mild intellectual disability.

Causes

Kniest dysplasia is a genetic disorder, meaning it‘s caused by changes in a person‘s genes. These changes can be inherited from a parent or occur spontaneously during the formation of the egg or sperm. In most cases, the disorder is caused by a mutation in the COMP gene. Mutations in the RMRP gene are less common.

The COMP gene provides instructions for making a protein that helps build and maintain cartilage, the tough, flexible tissue found in joints. Mutations in this gene can lead to the production of an abnormal or missing COMP protein, which affects cartilage formation and bone development.

Inheritance/recurrence risk

Inheritance or Recurrence Risk

Kniest dysplasia can be inherited in an autosomal dominant pattern. This means that if one parent carries the mutated gene, there‘s a 50% chance of passing it on to their child. It‘s also possible for the mutation to occur spontaneously, without a family history of the disorder. The risk of recurrence in future pregnancies depends on whether the mutation was inherited or spontaneous. If a parent carries the mutated gene, there‘s a 50% chance of passing it on with each pregnancy. If the mutation is spontaneous, the risk of recurrence is much lower.

WES Whole Exome Sequencing