Meier-Gorlin syndrome 1

Meier-Gorlin syndrome (MGS) is a rare genetic disorder characterized by a distinct set of clinical features.

• Small ears (microtia): One of the hallmark features of MGS, microtia refers to abnormally small ears.
• Absent or small kneecaps (patellae): Individuals with MGS often have either absent or significantly smaller kneecaps than usual.
• Short stature: People with MGS typically experience short stature, which is a significant aspect of the disorder.

These three clinical features - microtia, absent or small patellae, and short stature - are commonly observed in individuals with Meier-Gorlin syndrome [1][2][3].

References: [1] Meier-Gorlin syndrome (MGS) is characterized by the triad of microtia, absent or small patellae and short stature. At least two of these three clinical features must be present for a diagnosis to be made. [Context 2] [2] Meier-Gorlin syndrome (MGS) is an autosomal recessive disorder characterized by microtia, patellar aplasia/hypoplasia, and short stature. [Context 5] [3] Meier–Gorlin syndrome (MGS) is a rare genetic developmental disorder that causes primordial proportional dwarfism, microtia, the absence of or hypoplastic kneecaps, and short stature. [Context 6]

Meier-Gorlin Syndrome Signs and Symptoms

Meier-Gorlin syndrome (MGS) is a rare genetic disorder characterized by several distinct signs and symptoms. The main features of MGS include:

• Small ears (microtia): One of the most distinctive characteristics of MGS, small ears can be either absent or very small in size [1].
• Absent or small kneecaps (patellae): Individuals with MGS often have patellar aplasia or hypoplasia, which means their kneecaps are either missing or underdeveloped [3][8].
• Short stature: People with MGS typically experience short stature, which is a significant aspect of the condition [2][5].

In addition to these primary features, individuals with MGS may also exhibit other signs and symptoms, such as:

• Hearing loss: Some people with MGS may experience hearing difficulties due to their small ear canals [6].
• Feeding problems: Infants with MGS might face challenges with feeding, which can be a concern for parents and caregivers [5].
• Respiratory tract abnormalities: Individuals with MGS may have issues with their respiratory system, including narrow chest or persistent respiratory manifestations [4].
• Small chin and head size: Some people with MGS may have a small chin and head size compared to others [6].

It's essential to note that each individual with Meier-Gorlin syndrome can exhibit unique signs and symptoms. A comprehensive medical evaluation is necessary for an accurate diagnosis.

References: [1] Context result 1 [2] Context result 2 [3] Context result 3 [4] Context result 4 [5] Context result 5 [6] Context result 6 [7] Context result 7 [8] Context result 8

Meier-Gorlin syndrome (MGS) is a rare genetic disorder, and diagnostic testing plays a crucial role in confirming the diagnosis.

Genetic Testing

Genetic analysis is recommended for individuals with a personal and/or family history of MGS to ensure an accurate diagnosis. The goal of genetic testing is to identify mutations in one of the five pre-replication genes associated with MGS (CDC45, CDC6, CDT1, GMNN, and ORC1) [9][10].

Clinical Molecular Genetics Test

A clinical molecular genetics test for Meier-Gorlin syndrome 1 is available, which includes sequence analysis of the entire coding region. This test can be ordered through a laboratory that offers this service [13].

Next-Generation Sequencing (NGS)

The Meier-Gorlin syndrome NGS panel consists of eight genes: CDC45, CDC6, CDT1, GMNN, MCM5, ORC1, ORC4, and ORC6. Copy number variation (CNV) analysis of the Meier-Gorlin syndrome genes is also offered as a panel [14].

High-Throughput Sequencing

High-throughput sequencing has become a standard first-tier approach for both diagnostics and research-based genetic testing. This method can be used to identify mutations in the pre-replication genes associated with MGS [15].

In summary, diagnostic tests for Meier-Gorlin syndrome 1 include:

• Genetic analysis to identify mutations in one of the five pre-replication genes
• Clinical molecular genetics test for sequence analysis of the entire coding region
• Next-generation sequencing (NGS) panel consisting of eight genes associated with MGS
• High-throughput sequencing for identifying mutations in the pre-replication genes

These diagnostic tests can aid in confirming the diagnosis of Meier-Gorlin syndrome 1 and provide valuable information for genetic counseling and family planning.

Treatment Options for Meier-Gorlin Syndrome

Meier-Gorlin syndrome (MGS) is a rare genetic disorder characterized by short stature, bilateral microtia, and patellar aplasia/hypoplasia. While there is no cure for MGS, various treatment options are available to manage its symptoms.

Growth Hormone Treatment

One of the most effective treatments for MGS is growth hormone therapy. According to a study published in 2015 [1], growth hormone treatment was effective in only four patients with MGS, one with ORC4 mutations, one with CDC6 mutations, and two without mutations. However, another study from the same year [7] reported positive results for two males without mutations who received growth hormone therapy.

Other Treatment Options

While growth hormone treatment shows promise, it is not effective in most patients with MGS. In such cases, other treatment options may be considered to manage symptoms and improve quality of life. These may include:

• Physical therapy to maintain muscle strength and mobility
• Orthopedic interventions for patellar aplasia/hypoplasia
• Audiological evaluations and hearing aids for bilateral microtia

Pharmacological Implications

In some cases, pharmacological interventions may be necessary to manage associated problems in MGS patients. For example, if raised intracranial pressure is suspected, a rapid-acting nondepolarizing muscle relaxant may be preferable [8].

It's essential to note that each patient with MGS is unique, and treatment plans should be tailored to their individual needs.

References:

[1] de Munnik SA. (2015) Clinical features of Meier-Gorlin syndrome: a review. [Context result 7]

[2] Shawky RM. (2014) Meier-Gorlin syndrome: a rare autosomal recessive disorder. [Context result 10]

[3] de Munnik SA. (2012) Growth hormone therapy in Meier-Gorlin syndrome. [Context result 6]

[4] de Munnik SA. (2015) Growth hormone treatment in Meier-Gorlin syndrome: a case series. [Context result 3]

[5] Wescott R. (2023) Sustained hedgehog inhibitor treatment for basal cell carcinoma. [Context result 5]

[6] NORD. (n.d.) Meier-Gorlin Syndrome. [Context result 2]

[7] de Munnik SA. (2012) Growth charts of two patients with Meier–Gorlin syndrome showing a positive response to growth hormone treatment. [Context result 9]

[8] Pharmacological implications for raised intracranial pressure. [Context result 8]

Meier-Gorlin Syndrome Differential Diagnosis

Meier-Gorlin syndrome (MGS) can be challenging to diagnose due to its high clinical variability and genetic heterogeneity. However, several conditions share similar features with MGS, making differential diagnosis essential.

• Genitopatellar syndrome: This rare genetic disorder also presents with small kneecaps (patellae), short stature, and other skeletal abnormalities.
• Patellar aplasia-hypoplasia: A condition characterized by the absence or underdevelopment of the kneecap, which can be seen in MGS patients.
• Radial and patellar aplasia/hypoplasia: This rare congenital disorder involves the underdevelopment or absence of both the kneecap and radial bones.

Key Features to Consider

When differentiating MGS from other conditions, consider the following key features:

• Small ears (microtia)
• Absent or small kneecaps (patellae)
• Short stature
• Other skeletal abnormalities, such as unusually narrow long bones in the arms and legs

Genetic Heterogeneity

MGS is an autosomal recessive disorder, meaning that individuals must inherit two copies of the mutated gene (one from each parent) to express the condition. This genetic heterogeneity can make diagnosis more challenging.

Clinical Variability

The clinical presentation of MGS can vary significantly among affected individuals, making it essential to consider a range of possible diagnoses when evaluating patients with similar symptoms.

Citations:

• [1] - Meier-Gorlin syndrome (MGS) is an autosomal recessive disorder characterized by microtia, patellar aplasia/hypoplasia, and short stature. [6]
• The association of microtia, patellar anomalies, and short stature as such has not been described in other syndromes. [2]
• Skeletal symptoms overlapping with other syndromes make MGS difficult to diagnose clinically. [9]