Greenberg dysplasia
Greenberg dysplasia is a rare, prenatally lethal genetic disorder characterized by severe bone abnormalities, including a distinctive "moth-eaten" skeletal appearance and extensive fluid accumulation in the fetus.
Overview
Greenberg dysplasia is a severe condition characterized by specific bone abnormalities in the developing fetus. This condition is fatal before birth.
Symptoms & Skeletal Abnormalities
The bones of affected individuals do not develop properly, resulting in several distinct skeletal and physical features:
- A distinctive spotted appearance called moth-eaten bone, which is visible on x-ray images.
- Abnormal calcium deposits outside of normal bone structures (ectopic calcification).
- Extremely short bones in the arms and legs.
- Abnormally flat vertebrae (platyspondyly).
- Short ribs and extra fingers (polydactyly).
- Extensive swelling of the body caused by fluid accumulation (hydrops fetalis).
Because of these key characteristics, the condition is also known as hydrops-ectopic calcification-moth-eaten skeletal dysplasia (HEM).
Frequency
Greenberg dysplasia is a very rare condition. Approximately ten cases have been reported in the scientific literature.
Causes
Mutations in the LBR gene cause Greenberg dysplasia. This gene provides instructions for making a protein called the lamin B receptor. One region of this protein, called the sterol reductase domain, plays an important role in the production (synthesis) of cholesterol.
Cholesterol is a type of fat produced in the body and obtained from animal-derived foods (such as eggs, meat, fish, and dairy products). It is necessary for normal embryonic development and has important functions both before and after birth. It is an important component of cell membranes and the protective substance covering nerve cells (myelin). Additionally, cholesterol plays a role in the production of certain hormones and digestive acids. During cholesterol synthesis, the sterol reductase function of the lamin B receptor allows the protein to perform one of several steps that convert a molecule called lanosterol to cholesterol.
LBR gene mutations involved in Greenberg dysplasia lead to a loss of
