acromesomelic dysplasia, Maroteaux type

Acromesomelic Dysplasia, Maroteaux Type: A Rare Autosomal Recessive Skeletal Disorder

Acromesomelic dysplasia, Maroteaux type (AMDM) is a rare autosomal recessive skeletal disorder that affects skeletal growth. It is characterized by severe dwarfism, with adult height typically less than 120 cm [1]. The most characteristic features of this condition are extremely short limbs, with the legs more severely affected than the upper limbs [4].

Key Features:

• Severe dwarfism (adult height <120 cm)
• Extremely short limbs, with legs more severely affected than upper limbs
• Hands and feet are also significantly shortened

Inheritance Pattern: AMDM is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition [8].

Prevalence: The prevalence of AMDM is extremely low, with fewer than 1 in 1 million people affected [8].

Age of Onset: Symptoms typically become apparent in infancy or early childhood.

Overall, acromesomelic dysplasia, Maroteaux type is a rare and severe skeletal disorder that affects postnatal growth and development.

Acromesomelic dysplasia, Maroteaux type (AMDM) is a rare autosomal recessive skeletal disorder that affects skeletal growth. The primary features of AMDM include:

• Severe short stature: Individuals with AMDM are significantly shorter than their peers, with an average adult height below 120 cm [4][6].
• Shortening of the limbs: The middle and distal segments of the arms and legs are severely shortened, resulting in a characteristic "short-limb dwarfism" appearance [10][11].
• Vertebral anomalies: Vertebral shortening and deformity are common features of AMDM [14].
• Normal facial appearance and intelligence: Individuals with AMDM typically have normal facial features and intelligence quotient (IQ) levels [3].

Other symptoms may include:

• Growth retardation: Delayed bone maturation and growth retardation are characteristic features of AMDM [4][5].
• Abnormal shortening of the bones in the hands and feet: Acromelia, a condition characterized by abnormally short hands and feet, is often associated with AMDM [4][10].

It's essential to note that each individual with AMDM may exhibit unique symptoms, and the severity of these features can vary widely among affected individuals.

Diagnostic Tests for Acromesomelic Dysplasia, Maroteaux Type

Acromesomelic dysplasia, Maroteaux type (AMDM) is a rare autosomal recessive disorder characterized by severe dwarfism and skeletal abnormalities. Diagnostic tests are essential to confirm the diagnosis of AMDM.

• Sequence analysis: Sequence analysis of the entire coding region of the NPR2 gene can be performed to detect mutations associated with AMDM [1, 8]. This test is recommended for individuals with a personal and/or family history of this disorder.
• Bi-directional sequencing: Bi-directional sequencing of the NPR2 gene can also be used to identify mutations in individuals suspected of having AMDM [2].
• PCR amplification: PCR amplification of the exons of the NPR2 gene can be performed to detect mutations associated with AMDM [8].
• Genetic analysis: Genetic analysis, including sequence analysis and PCR amplification, is essential for providing a molecular diagnosis of this disorder.

Additional Tests

While not specific to AMDM, other tests may also be used in conjunction with genetic analysis to confirm the diagnosis. These include:

• Radiological findings: Radiological findings, such as skeletal abnormalities and short stature, can be important for the diagnosis of AMDM [9].
• Clinical evaluation: A thorough clinical evaluation, including a review of medical history and physical examination, is essential for confirming the diagnosis of AMDM.

References

[1] Context 2 [2] Context 3 [8] Context 8 [9] Context 9

Treatment Options for Acromesomelic Dysplasia, Maroteaux Type (AMDM)

While there is no specific cure for AMDM, various treatment options are available to manage the symptoms and improve quality of life. Here are some of the key points related to drug treatment:

• Palliative care: Treatment is generally aimed at palliating symptoms, such as kyphosis and lumbar hyperlordosis [9].
• Growth hormone (GH) treatment: GH treatment has been utilized in children with skeletal dysplasia, including AMDM, to improve height outcomes. However, the effectiveness of GH treatment for AMDM specifically is not well established [7].
• Drug repurposing: Drug repurposing is a proposed strategy for treating achondroplasia, which shares some similarities with AMDM. Meclozine, an anti-histamine and motion sickness drug, was considered as a putative treatment for achondroplasia, but its effectiveness for AMDM is unknown [6].
• Targeted pharmacologic therapy: Vosoritide is the only targeted pharmacologic therapy for achondroplasia that has proceeded to human clinical trial. However, its efficacy and safety in treating AMDM are not established [10].

It's essential to note that treatment options for AMDM may vary depending on individual cases and should be discussed with a healthcare professional.

References:

[6] Legeai-Mallet L (2020) Cited by 50 — Drug repurposing is also a proposed strategy for achondroplasia. Meclozine, an anti-histamine and motion sickness drug was considered as putative treatment, as ...

[7] Nov 25, 2020 — GH treatment in children with skeletal dysplasia has been utilised to improve height outcomes. Several groups reported positive short- and ...

[9] Treatment is individualized but is generally aimed at palliating symptoms, for example, treatment of kyphosis and lumbar hyperlordosis. Acromesomelic dysplasia.

[10] Yap P (2016) Cited by 15 — Vosoritide is the only targeted pharmacologic therapy for achondroplasia that has proceeded to human clinical trial. The results from the Phase ...

The differential diagnosis for acromesomelic dysplasia, Maroteaux type (AMD1) includes several conditions that present with similar clinical features.

• Pseudohypoparathyroidism: This condition can be differentiated from AMD1 by the presence of dwarfism and normal vertebrae in pseudohypoparathyroidism, whereas AMD1 is characterized by severe disproportionate short stature without dwarfism.
• Acrodysostosis: Acrodysostosis also presents with hand findings similar to AMD1, but can be differentiated by the lack of dwarfism and normal vertebrae in AMD1.
• Other skeletal dysplasias: Other skeletal dysplasias such as spondylometaphyseal dysplasia (Type IV: Brahimi-Bacha Type) and campailla-martinelli type, which present with severe limb shortening and metaphyseal changes, can also be considered in the differential diagnosis.

It's worth noting that the cardinal signs for the diagnosis of AMD1 include severe disproportionate short stature with extremely shortened middle and distal segments of both the upper and lower limbs, as well as a prominent forehead and short stubby fingers with redundant skin on hands [10].

The presence of these clinical features can help differentiate AMD1 from other skeletal dysplasias and conditions that present with similar symptoms.

References: [1] Zabel B, Thomeer RT, Zonderland HM, et al. (1998) Acromesomelic dysplasia Maroteaux type maps to human chromosome 9. Am J Hum Genet. 63:155-62 (PMID: 9634515) [10] Expand 13.1 Acromesomelic Dysplasia, Maroteaux Type (MIM 602875)