Meier-Gorlin syndrome

Alternate names

Ear, patella, short stature syndrome; Microtia, absent patellae, micrognathia syndrome

Definition

Meier-Gorlin syndrome (MGS) is a very rare inherited condition characterized by very small ears and ear canals, short stature, and absent or very small kneecaps (patellae).

Epidemiology

Meier-Gorlin syndrome is a rare condition; however, its prevalence is unknown.

Cause

• Meier-Gorlin syndrome can be caused by mutations in one of several genes.
• Each of these genes, ORC1, ORC4, ORC6, CDT1, and CDC6, provides instructions for making one of a group of proteins known as the pre-replication complex.
• This complex regulates initiation of the copying (replication) of DNA before cells divide.
• Specifically, the pre-replication complex attaches (binds) to certain regions of DNA known as origins of replication, allowing copying of the DNA to begin at that location.
• This tightly controlled process, called replication licensing, helps ensure that DNA replication occurs only once per cell division and is required for cells to divide.

Gene mutations

• Mutations in any one of these genes impair formation of the pre-replication complex and disrupt replication licensing; however, it is not clear how a reduction in replication licensing leads to Meier-Gorlin syndrome.
• Researchers speculate that such a reduction delays the cell division process, which impairs growth of the bones and other tissues during development. Some research suggests that some of the pre-replication complex proteins have additional functions, impairment of which may contribute to features of Meier-Gorlin syndrome, such as delayed development of the kneecaps and ears.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Signs and symptoms

• It is considered a form of primordial dwarfism because the growth problems begin before birth (intrauterine growth retardation).
• After birth, affected individuals continue to grow at a slow rate.
• Other characteristic features of this condition are underdeveloped or missing kneecaps (patellae), small ears, and, often, an abnormally small head (microcephaly).
• Despite a small head size, most people with Meier-Gorlin syndrome have normal intellect.
• Some people with Meier-Gorlin syndrome have other skeletal abnormalities, such as unusually narrow long bones in the arms and legs, a deformity of the knee joint that allows the knee to bend backwards (genu recurvatum), and slowed mineralization of bones (delayed bone age).
• Most people with Meier-Gorlin syndrome have distinctive facial features.
• In addition to being abnormally small, the ears may be low-set or rotated backward.
• Additional features can include a small mouth (microstomia), an underdeveloped lower jaw (micrognathia), full lips, and a narrow nose with a high nasal bridge.
• Abnormalities in sexual development may also occur in Meier-Gorlin syndrome.
• In some males with this condition, the testes are small or undescended (cryptorchidism).
• Affected females may have unusually small external genital folds (hypoplasia of the labia majora) and small breasts. Both males and females with this condition can have sparse or absent underarm (axillary) hair.
• Additional features of Meier-Gorlin syndrome can include difficulty feeding and a lung condition known as pulmonary emphysema or other breathing problems.

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Abnormality of epiphysis morphology(Abnormal shape of end part of bone)
• Anotia
• Atresia of the external auditory canal(Absent ear canal)
• Clinodactyly of the 5th finger(Permanent curving of the pinkie finger)
• Cryptorchidism(Undescended testes)
• Delayed skeletal maturation(Delayed bone maturation)
• Failure to thrive(Faltering weight)
• Feeding difficulties(Feeding problems)
• Intrauterine growth retardation(Prenatal growth deficiency)
• Joint hyperflexibility(Joints move beyond expected range of motion)
• Mandibular aplasia(Failure of development of lower jaw)
• Microcephaly(Abnormally small skull)
• Micrognathia(Little lower jaw)
• Microtia, third degree
• Narrow mouth(Small mouth)
• Retrognathia(Receding chin)
• Severe short stature(Dwarfism)
• Slender long bone(Long bones slender)

30%-79% of people have these symptoms

• Abnormality of the ribs(Rib abnormalities)
• Aplastic clavicle(Absent collarbone)
• Camptodactyly of finger(Permanent flexion of the finger)
• Clitoral hypertrophy(Enlarged clitoris)
• Clitoral hypoplasia(Small clitoris)
• Craniosynostosis
• High, narrow palate(Narrow, high-arched roof of mouth)
• Hypoplasia of the maxilla(Decreased size of maxilla)
• Hypoplastic labia majora(Small labia majora)
• Hypoplastic labia minora(Underdeveloped inner lips)
• Low-set ears(Low set ears)
• Patellar aplasia(Absent kneecap)
• Posteriorly rotated ears(Ears rotated toward back of head)
• Respiratory distress(Breathing difficulties)
• Respiratory failure

5%-29% of people have these symptoms

• Bifid uvula
• Breast aplasia(Absent breast)
• Elbow dislocation(Dislocations of the elbows)
• Epispadias
• Global developmental delay
• Hearing impairment(Deafness)
• Hypoplasia of penis(Underdeveloped penis)
• Hypospadias
• Intellectual disability(Mental deficiency)
• Specific learning disability
• Submucous cleft hard palate
• Thick vermilion border(Full lips)

Diagnosis

MGS is diagnosed based on the clinical signs and symptoms.

Treatment

Treatment is based on the symptoms. Most people with this syndrome have normal lifespans.

NIH genetic and rare disease info

• NIH info on Meier-Gorlin syndrome

Meier-Gorlin syndrome is a rare disease.

Meier-Gorlin syndrome Resources
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