Overview

Acromesomelic dysplasia is an extremely rare, hereditary, progressive skeletal disorder that leads to one type of short stature known as short-limb dwarfism. The syndrome is characterized by acromelia and mesomelia. Mesomelia refers to the shortening of the bones of the lower legs and forearms compared with the upper parts of those limbs. When incorporated as acromelia, the term simply means the shortening of the bones of hands and feet. Thus, proportional short stature in affected individuals results from unusually short forearms and abnormal shortening of bones of the lower legs. Other characteristic features are the very short hands, fingers, feet, and toes.¹

Types

AMDs can be subclassified by using Nosology and Classification of Genetic Skeletal Disorders.

Acromesomelic dysplasia Maroteaux type

AMDM type was reported in 1971. Transmits in an autosomal recessive manner involving a particular form of dwarfism with a height below 120 cm known as acromesomelic dwarfism or short-limb dwarfism. Virtually, it is reported in 40 – 50 cases of AMDM. The phenotype is generally visualized at or can be seen during birth and becomes more evident during the early age of life; the first 2 years of life.² The characteristic features are:

• Skeletal abnormalities: Marked shortening of the bones of the forearms and lower legs, a characteristic finding in this disorder that generally causes short spareness. Changes in the hands and feet are also noted as associated with this condition – shortened, broad fingers or toes are often seen
• Facial features: In Acromesomelic Dysplasia, Maroteaux type, there are strikingly less-notable facial features. Some of the MPS VI, however, might reveal mild facial dysmorphisms of a grotesque type
• Genetic basis: The inheritance pattern of the disorder is autosomal recessive, which means to manifest; the child should have a parental carrier to transmit a mutated gene copy each³

Acromesomelic dysplasia, Grebe type

It is the autosomal recessive, severe form of acromesomelic dysplasia. AMDG is phenotyped by severely short and abnormal 100 cm of adult stature including both of the fore and the hind limbs. This increase, however, is in a proximal to distal direction; the severity of limb malformation means that the hands and feet are largely affected, and that categorizes it as a type of acromesomelic dysplasia in the International Classification of Osteochondrodyspl.

Long bones show an exaggeratedly severe shortening with fusion in fingers and toes bones of long bones, a characteristic feature.⁴

Acromesomelic dysplasia, Hunter–Thompson type

The Hunter-Thompson type was first reported by Hunter and Thompson et al. in 1976.It is inherited in an autosomal-recessive pattern.² The features are:

• Severe limb shortening of both forearms and legs, including fingers and toes. This is because the deformity may also result in restricted movements of the joint by the patient
• The facial features include a broad forehead and flat nose, although these are mild in comparison with the limb deformity
• Shortened, stubby fingers and toes

 Du Pan syndrome

This type of acromesomelic dysplasia was described by Du Pan in 1924, hence called Du Pan syndrome. He described the case of this disease in a boy affected with a complex form of brachydactylia and bilaterally absent fibulae.

Another case, of two siblings, was reported by Grebe with extremity malformations and was similar to those reported by Du Pan back in 1924. This was later followed by Hunter and Thompson who reported a case of a woman with skeletal deformities that were also similar to those reported by Du Pan and Grebe respectively. This form of acromesomelic dysplasia is wrongly understood to be involved in

Other names are 1. Fibular hypoplasia and complex brachydactyly 2. Du Pan syndrome 3. Pickle Fork Hand Syndrome The condition follows an autosomal recessive trait of inheritance. In Du Pan syndrome, the abnormalities occur symmetrically in only the extremities, while the axial skeleton is normal. Du Pan syndrome includes symptoms like moderate short stature, fibula hypoplasia/dysplasia or aplasia, complex brachydactyly, severe hypoplastic/dysplastic anomalies of the hand/feet, and normal mental development. Among the affected individuals, the internationally reported families, the fingers of the hands, including the thumbs, are variously involved, with some even displaying radial deviation and a button-like thumb appearance.²

Acrosomelic dysplasia Demirhan type 

Demirhan type was studied in a 16-year-old girl from the same consanguinous family of pertinent Turkish origin by Demirhan et al., and It showed autosomal recessive inheritance.

It is characterized by disproportionate short stature involving severe acromesomelic limb shortening. The forearm is shorter compared to the upper arm. The trunk is of average length, and the hands of all fingers are present; the affected individuals have severe brachydactyly with radially deviated fingers. All fingernails are present. Phalangeal bones are severely hypoplastic. The metacarpals are almost of normal length. Both the thumbs seem to be there only with the distal phalanx as it appears that the proximal phalanges are missing. The carpal bones give an abnormal configuration, and a number of bones are fused. The ulna and the radius are short, and its radius is also broad with an expanded distal epiphysis. During the teenage years, the epiphyseal plate of the ulna and the radius have not yet closed. Bilateral clubfoot deformity, small broad feet, and short toes with constrictions at bases are associated with this disorder. The toenails are present.²

Causes

The pathogenic variants in acromesomelic dysplasia are genetic in nature. It is the result of genetic alteration either by inheritance between parents and children or, most commonly, begins with a mutation from random cell enlargement. Genetic mutations, on the other hand, could be through contracted viruses, environmental factors such as UV radiation due to sunlight exposure, or just a mix of these factors.

When it comes to genetic conditions, a classical belief determines these claims be traced back to the chromosomes received from the father and the mother.

Several disorders arise from recessive genetic disorders where a person inherits one such gene from both parents, both for the same trait. These carriers generally do not suffer the overt symptoms of the disease. In every pregnancy, the two carrier individuals are at a 25 percent risk that both of them will contribute the defective gene and therefore their child will be affected. There is a 50 percent level of risk in every pregnancy of having a child who turns out to be a carrier just like the parents are. The probability of the child inheriting normal genes from both parents is 25% and genetically normal for the trait. This is the same in both males and females.

Everybody has 4-5 odd genes in their genetic materials. Close blood-related parents are more likely to carry the same abnormal gene than parents who are not related by blood, increasing the likelihood of having a child with a recessive genetic disorder.

A dominant genetic disorder occurs when it takes only one abnormal gene to produce a specific disease. One faulty gene is expressed even if the matching gene on the other chromosome is normal. The abnormal gene can come from either parent or be a new mutation that first appears in the affected person. Each pregnancy has a 50% risk of passing the abnormal gene from the affected parent to the offspring. The risk is the same for both males and females.¹

Sign and symptoms

• Limb shortening: Acromesomelic dysplasia is the inhibition of the growth of long bones, that is, forearms and lower legs. They have short forearms and lower legs. They exhibit a short stature. These are observed during the first year of life
• Hand and foot deformities: Abnormal development of the cartilage can also result in changes in the bones in the hands and feet. This results in shortened fingers and toes
• Spinal deformities: The spinal deformities are not the primary characteristics of acromesomelic dysplasia but the secondary complications caused due to the deformity of limbs. Shortening of lower limbs can affect the alignment of the pelvis and lower spine. It can also result in lumbar lordosis, which is an inward curvature of the spine
• Abnormalities about the joint: Acromesomelic dysplasia involves bones in such a manner that abnormalities involve the bones and mobility and functions of the individual. Abnormal shortening of the limbs leads to tightness of the ligaments and tendons around the joints, causing limitations in the movement of joints like that of the knee, elbow, and fingers. Because of this, bowing of the legs and knock-knees often occur; the knee deformity causes a gait abnormality
• Facial features: flattened faces and small noses which are generally flat. Marked with macrocephaly and prominent occipital
• Degeneration, rigidity, deep touch tenderness, and pain in the joint may happen due to elbow–osteoarthritis

Diagnosis

• Physical examination: Acromesomelic dysplasia can be diagnosed in the initial years of life during a physical examination at a clinic, where the detailed patient history, family history, and characteristic examination can aid in understanding the abnormality
• X-ray 
• Genetic testing: Analyzes the specific diagnosis and peculiar syndromes on a genetic level

Treatment

Orthopaedic surgeons are such doctors who carry out the necessary surgery and treatment associated with bones. Acromesomelic conditions can degrade with time, affecting the life quality if treatments are not given in time.⁵

• Surgical procedure: Limb shortening is exhibited in acromesomelic dysplasia presenting as spinal, knee, and elbow deformities which can, in turn, become restrictive in mobility and also disfiguring in appearance. To give better mobility and good stature, surgical elongation of the limb can be done. The benefits of surgical correction of joint deformities are it gives the patient an enhanced correction of deformity and increased mobility
• Physical therapy and rehabilitation: The physical therapist deals with a patient suffering from acromesomelic dysplasia and gives him personalized exercises based on his deformity. This helps in increasing mobility and muscle strength, improving quality of life
• Orthotic devices: In these, there are braces and splints which give joint good support and alignment to maintain good posture and enable a person to move well
• Drug: Besides the joint deformity, pain can also be experienced among individuals with acromesomelic dysplasia; medicines are prescribed in this instance to lessen the pain
• Human genetic counselling: The genetic counsellors provide information about the pattern of inheritance of the genetic mutation, its chances to transmit further in the coming generations, and also family planning in order to avoid it. Living with acromesomelic dysplasia has severe physical and psychological challenges not only for the individual but also for the family members. Counselling helps people affected by acromesomelic dysplasia and their family members accept and move on concerning their health conditions

Summary 

Acromesomelic dysplasia is a very rare inherited disorder with an autosomal recessive mode of inheritance and is characterized by dwarfism with disproportionately short limbs, unusual at the mainland Chinese hospitals underreported. It adds that there are different identified types of the condition of acromesomelic dysplasia, and many signs, among which are severe limb shortening and hand or foot abnormalities.

Acromesomelic dysplasia is inherited from changes in the genetic material and can be diagnosed physically, with the help of X-rays, and genetically. This would then entail surgical interventions, physical therapy, orthotics and equipment, medication, genetic counselling, and psychological treatment to allow for the restoration of mobility in patients with acromesomelic dysplasia.