Meier-Gorlin syndrome
Rare genetic disorder with growth deficiency, ear and patellar abnormalities.
Meier-Gorlin syndrome, sometimes called ear-patella-short stature syndrome, is a rare genetic condition passed down in an autosomal recessive pattern. It primarily involves slowed growth before and after birth, missing or underdeveloped kneecaps, and small, malformed ears. The condition is classified as a type of microcephalic primordial dwarfism. As of 2024, fewer than 150 cases had been documented.
People with Meier-Gorlin syndrome typically show a classic set of three features: growth deficiency that begins in the womb and continues after birth, absent or underdeveloped kneecaps, and small, poorly formed ears. Almost all affected individuals have both kneecap issues and microtia (small ears). The severity of microtia varies widely, and the ears may also be low-set. Microtia can come with narrowing of the ear canal and conductive hearing loss. While most patients lack kneecaps entirely, some have kneecaps that are simply smaller than normal. Most are born with intrauterine growth restriction and continue to grow slowly after birth, though their growth rate often becomes nearly normal later. Another very common feature is a smaller-than-average head size (microcephaly).
Intellectual function is usually normal. Some individuals experience developmental delays without intellectual disability, and a few reported cases have involved mild intellectual disability. In females, breast tissue often fails to develop fully, and some individuals—male or female—may have abnormal genitalia, such as underdeveloped labia or undescended testicles. Secondary sex characteristics, like underarm or pubic hair, may also be affected. Pulmonary emphysema occurs in some cases. Craniosynostosis (early fusion of skull bones) is most commonly linked to mutations in the CDC45 gene (MGORS7), but it can also occur in other subtypes.
A diagnosis can be suspected based on classic signs like microtia and is confirmed through genetic testing.
The condition is genetically heterogeneous, meaning different gene mutations can cause the same disorder. Mutations in several genes have been linked to Meier-Gorlin syndrome, with one form (MGORS6) being inherited in an autosomal dominant pattern.
Quick Facts
- Synonym
- Ear-patella-short stature syndrome, MGORS
- Symptoms
- IUGR, short stature, patellar hypoplasia or aplasia, microtia, micromastia, pulmonary emphysema.
- Causes
- Mutations in the genes ORC1, ORC4, ORC6, CDT1, CDC6, CDC45L, MCM5, GMNN, GINS3, DONSON.
- Treatment
- Symptomatic
- Frequency
- 1-9:1 000 000
- Types
- 8
Facts from the source article.
Lore & Background
Meier-Gorlin syndrome was first described by Meier and colleagues in 1959, and later by Gorlin and colleagues in 1975. The disorder is characterized by a classic triad of pre- and postnatal growth deficiency, patellar aplasia or hypoplasia, and underdevelopment of both ears. Most patients have normal intellectual functioning, though some have developmental delays without intellectual disability; a few cases of mild intellectual disabilities have been recorded. Female patients often experience underdevelopment of breast tissue, and some have abnormal genitalia or affected secondary sex characteristics. Pulmonary emphysema can also occur.
Reader's Guide
Meier-Gorlin syndrome is significant as a rare genetic disorder that provides insight into the pre-replication complex and cell cycle regulation. The syndrome is caused by mutations in genes encoding components of the pre-replication complex, including ORC1-6, CDC6, CDT1, MCM2-7, and CDC45L, which impair DNA replication and cause growth restriction. GMNN mutations are autosomal dominant gain-of-function mutations that hyperactivate the protein, inhibiting replication longer through CDT1 destruction. Some proteins linked to MGORS have non-canonical functions, such as ORC6 stimulating cytokinesis and participating in MMR, CDT1 stabilizing kinetochore-microtubule interactions, and ORC1 regulating centrosome and centriole replication. Management focuses on growth retardation, hearing loss, floating kneecap, feeding issues, gonarthrosis, knee pain, and pulmonary problems. Growth hormone therapy has been tried but was effective only in some cases.
Did You Know?
- Fewer than 150 cases had been recorded as of 2024.
- Most patients have normal intellectual functioning; only one had mild intellectual disabilities.
- Craniosynostosis is mainly associated with CDC45L (MGORS7) mutations.
More in Growth disorders 1-24
Spotted an error? Know more?
Reader corrections go straight into our review queue. Suggest an edit · How this site is sourced