Meier-Gorlin syndrome

Meier-Gorlin syndrome is a form of primordial dwarfism primarily characterized by short stature, underdeveloped or missing kneecaps, and small ears.

Overview

Meier-Gorlin syndrome is a condition primarily characterized by short stature. Because growth problems begin before birth, it is considered a form of primordial dwarfism. After birth, affected individuals continue to grow at a slow rate. Despite often having an abnormally small head (microcephaly), most people with the syndrome have normal intellect.

Physical Characteristics

• Skeletal: Underdeveloped or missing kneecaps (patellae), narrow long bones, and delayed bone mineralization.
• Facial: Small ears that may be low-set or rotated backward, a small mouth (microstomia), an underdeveloped lower jaw (micrognathia), and a narrow nose with a high nasal bridge.
• Sexual Development: Males may have small or undescended testes (cryptorchidism). Females may have small external genital folds and small breasts. Both sexes may have sparse or absent underarm hair.

Causes

Meier-Gorlin syndrome is caused by mutations in genes such as ORC1, ORC4, ORC6, CDT1, and CDC6. These genes provide instructions for making proteins that form the pre-replication complex, which regulates the initiation of DNA replication before cell division.

Mutations impair the formation of this complex and disrupt replication licensing. Researchers believe this delay in the cell division process impairs the growth of bones and other tissues during development.

Inheritance

This condition is inherited in an autosomal recessive pattern, meaning both copies of the gene in each cell have mutations. Parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene but typically do not show signs of the condition.