Meier-Gorlin syndrome (MGS) is a rare genetic disorder impacting growth and development from before birth. It is a form of primordial dwarfism, where slowed growth begins in the womb and continues throughout life. Due to its rarity, the exact prevalence of MGS is unknown.
Core Physical Characteristics
Individuals with Meier-Gorlin syndrome often display a distinct set of physical features. Three common characteristics are primordial dwarfism, microtia, and aplasia or hypoplasia of the patellae. Primordial dwarfism means severely short stature with restricted growth before and after birth. Microtia involves small or underdeveloped outer ears. Aplasia or hypoplasia of the patellae refers to absent or underdeveloped kneecaps.
Other physical traits can also be present. Many individuals have microcephaly, a smaller than average head size, though this typically does not affect intellectual ability. Facial features may include a small mouth (microstomia), an underdeveloped lower jaw (micrognathia), full lips, and a narrow nose with a high nasal bridge. Skeletal anomalies are common, such as unusually narrow long bones, genu recurvatum (knee bending backward), and delayed bone mineralization. Sparse or absent underarm hair and certain urogenital abnormalities, like undescended testes or underdeveloped external genitalia, can also occur.
Genetic Origins and Inheritance
Meier-Gorlin syndrome arises from genetic mutations that disrupt normal cellular processes. It is caused by changes in genes that provide instructions for proteins forming the pre-replication complex. This complex regulates DNA replication before cells divide, a process essential for growth and development. When these genes are altered, the complex’s formation is impaired, delaying cell division and affecting the growth of bones and other tissues.
Several genes cause MGS, including ORC1, ORC4, ORC6, CDT1, and CDC6. Mutations in ORC1 and ORC4 are often associated with more severe short stature and microcephaly. The most common inheritance pattern is autosomal recessive. This means an individual must inherit two copies of a mutated gene, one from each parent, to develop the condition. Both parents are typically unaffected carriers, carrying one copy of the altered gene without showing symptoms.
Diagnosis and Evaluation
Diagnosis of Meier-Gorlin syndrome typically begins with a clinical assessment. A doctor observes characteristic physical features, such as short stature, ear appearance, and the presence or absence of kneecaps. While some individuals may display all three primary features, a diagnosis may still be considered if at least two are present. Prenatal ultrasounds might offer clues like intrauterine growth restriction or a smaller jaw, though these are not definitive for MGS alone.
Imaging studies confirm suspected skeletal anomalies. X-rays evaluate bone development and confirm the patellae’s state, especially in older children where kneecaps are visible. For infants and young children, ultrasound of the kneecaps is preferred, as patellae are not fully mineralized on X-rays until around five or six years. Molecular genetic testing is the definitive diagnostic step, analyzing DNA to pinpoint specific mutations in genes known to cause MGS.
Management of Associated Health Conditions
There is no cure for Meier-Gorlin syndrome, so management addresses specific health issues and symptoms. A multidisciplinary team of specialists provides comprehensive care. Hearing loss, often associated with microtia or narrow ear canals, may be managed with hearing aids or surgical options for ear reconstruction.
Physical and occupational therapy help individuals with mobility and joint issues, especially those related to underdeveloped or absent kneecaps, which can lead to instability, pain, and early arthritis. Infants may experience feeding difficulties and poor weight gain, requiring feeding support. Regular orthopedic monitoring addresses potential knee problems and other skeletal abnormalities. While intelligence is typically unaffected, some individuals may experience delayed motor or speech development, for which speech therapy can be helpful. Respiratory issues, such as congenital pulmonary emphysema, are also possible and require monitoring and preventative measures like vaccinations.