Hypochondroplasia: Definition, Symptoms, Causes, Related Disorders, Diagnosis and Treatment

Short stature is often not recognized until early childhood or, in some cases, into adulthood.

Hypochondroplasia is a genetic disorder characterized by small stature and disproportionately short arms, legs, hands, and feet (short-limbed dwarfism).

In those with the disorder, the tilt of the legs usually develops during early childhood, but often improves spontaneously with age.

Some affected individuals may also have an abnormally large head (macrocephaly), a relatively prominent forehead, and / or other physical abnormalities associated with the disorder. Also, in about 10 percent of cases, there may be mild mental retardation.

In some cases, hypochondroplasia appears to occur randomly for unknown reasons (sporadically) with no apparent family history. In other cases, the disorder is familial with autosomal dominant inheritance.

Signs and symptoms of hypochondroplasia

Hypochondroplasia is characterized primarily by short stature , disproportionately short arms and legs (limbs), mild to moderate shortening of the fingers and toes (brachydactyly), and short hands and feet (i.e., short limb dwarfism).

Slow growth is often not apparent at birth; As noted above, it may not be recognized until about two to three years of age, later in childhood, or into adulthood.

In those with hypochondroplasia, limb shortening can be relatively mild or moderate. During early childhood, the outward tilt of the legs (ie, bowlegs [genu varum]) typically appears to be pronounced during weight bearing.

This condition often improves spontaneously later in childhood. Many affected people also have limited extension and rotation of the elbows. Also, beginning in childhood, exercise can cause mild pain or discomfort in the elbows, knees, and / or ankles.

In affected adults, such joint pain can extend to the lower back. About one-third may also have an abnormally pronounced inward curvature of the lower back spine (lordosis).

Some people with hypochondroplasia also have an abnormally large head (macrocephaly).

Also, the skull may be relatively wide and short (brachycephaly) or rectangular in shape with a slightly prominent forehead. However, the facial appearance is typically normal.

Reports indicate that mild mental retardation may also be present in about 10 percent of affected people.

Causes

In some cases, hypochondroplasia appears to occur randomly for unknown reasons (sporadically) with no apparent family history of the disorder.

According to the researchers, such cases typically represent new (sporadic) genetic changes (mutations) that can be transmitted as an autosomal dominant trait (i.e. new dominant genetic mutations).

Researchers have observed an older age of the father (advanced paternal age) in some cases of apparently sporadic hypochondroplasia.

Familial cases of the disorder have also been reported. In such cases, the disorder is autosomal dominant.

Human traits, including classic genetic diseases, are the product of the interaction of two genes, one received from the father and the other from the mother.

In dominant disorders, a single copy of the disease gene (received from either the mother or the father) can be expressed by “dominating” the other normal gene and resulting in the onset of the disease.

The risk of transmitting the disorder from the affected father to the offspring is 50 percent for each pregnancy, regardless of the sex of the resulting child. The risk is the same for each pregnancy.

Researchers indicate that hypochondroplasia often appears to be the result of specific mutations in a gene known as “fibroblast growth factor receptor 3” (FGFR3). The FGFR3 gene is located on the short (p) arm of chromosome 4 (4p16.3).

Chromosomes are found in the nucleus of every cell in the body. They carry the genetic characteristics of each individual.

Human chromosome pairs are numbered 1 through 22, with a different 23 pair of X and Y chromosomes for males and two X chromosomes for females.

Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q”. Chromosomes are subdivided into bands that are numbered. Therefore, chromosome 4p16.3 refers to band 16.3 on the short arm of chromosome 4.

Researchers have also found that different mutations of the same gene (i.e., FGFR3) can cause achondroplasia, indicating that hypochondroplasia and achondroplasia are allelic disorders.

Achondroplasia is a more severe form of short-limbed dwarfism that can be characterized by certain features similar to those seen in hypochondroplasia.

Genetic analysis has revealed that some individuals with hypochondroplasia currently have no identified mutations of the FGFR3 gene.

In such cases, the researchers suggest that the disorder may be the result of mutations in different disease genes (genetic heterogeneity) or possibly other currently undetected FGFR3 gene mutations.

More research is needed to learn more about the underlying genetic causes of hypochondroplasia.

Affected populations

Hypochondroplasia appears to affect women and men in relatively equal numbers. The characteristics of the disorder were originally reported in 1913; hypochondroplasia was described as a distinct disease entity in 1924.

Since then, more than 100 cases have been recorded in the medical literature, including isolated (sporadic) and family cases. Hypochondroplasia is believed to have an incidence of approximately one twelfth of achondroplasia.

Incidence refers to the number of new cases of a particular disorder or condition during a specific period. The estimated frequency of achondroplasia has ranged from about one in 15,000 to one in 35,000 births.

Related disorders

The symptoms of the following disorders may be similar to those of hypochondroplasia. Comparisons can be useful for a differential diagnosis.

Achondroplasia is a genetic disorder characterized by short-limbed dwarfism that manifests at birth.

Although hypochondroplasia has certain similar findings, experts indicate that it can be distinguished from achondroplasia by:

  • Less severe skeletal malformations of the hands and spine.
  • Absence of pelvic involvement.
  • Lack of associated or relatively mild abnormalities of the skull and facial (craniofacial) region.
  • And other differences as determined by clinical and radiographic (radiographic) evaluation.

In individuals with achondroplasia, the regions of the extremities closest to the trunk (proximal regions), such as the upper arms and thighs, are typically shorter than distal or further away from the trunk (i.e., rhizomelic dwarfism) .

Additional characteristic findings include:

  • Unusually short hands.
  • A distinctive malformation in which the fingers assume a “three-pointed” position (ie, trident).
  • Increased tilt of the pelvis, causing abnormal prominence of the abdomen and buttocks.

Distinctive facial abnormalities are also often present, including:

  • An unusually large head (macrocephaly).
  • Prominent forehead.
  • Depressed nasal bridge.
  • Narrow nasal passages.
  • Unusually flat underdeveloped midface regions (midface hypoplasia).

Affected individuals may also have decreased elbow extension and rotation, abnormally pronounced inward curvature of the lower back spine (lordosis), and / or additional physical abnormalities.

In some cases, the disorder may be associated with potentially serious neurological complications. Achondroplasia usually appears to be due to new autosomal dominant (sporadic) genetic mutations.

On rare occasions, familial cases were reported in which the disorder was inherited as an autosomal dominant trait. As noted above, achondroplasia and hypochondroplasia can be the result of different mutations of the same gene (FGFR3).

The disorder can be associated with potentially serious neurological complications. Achondroplasia usually appears to be due to new autosomal dominant (sporadic) genetic mutations.

On rare occasions, familial cases were reported in which the disorder was inherited as an autosomal dominant trait.

As noted above, achondroplasia and hypochondroplasia can be the result of different mutations of the same gene (FGFR3).

The disorder can be associated with potentially serious neurological complications. Achondroplasia usually appears to be due to new autosomal dominant (sporadic) genetic mutations.

On rare occasions, familial cases were reported in which the disorder was inherited as an autosomal dominant trait.

As noted above, achondroplasia and hypochondroplasia can be the result of different mutations of the same gene (FGFR3). Achondroplasia and hypochondroplasia can be the result of different mutations of the same gene (FGFR3).

Achondroplasia and hypochondroplasia can be the result of different mutations of the same gene (FGFR3).

Additional genetic disorders may be characterized by short stature, disproportionately short arms and legs, wide and short hands and feet, abnormal head enlargement (macrocephaly), and / or other symptoms and findings similar to those potentially associated with hypochondroplasia.

Diagnosis of hypochondroplasia

As noted above, in individuals with hypochondroplasia, short stature often may not be recognized until early or middle childhood or into adulthood.

The disorder can be diagnosed based on a complete clinical examination; identification of characteristic physical findings (eg, short stature, brachydactyly, genu varum, macrocephaly); x-ray studies; and / or other diagnostic techniques.

Treatment of hypochondroplasia

Treatment of hypochondroplasia is directed at the specific symptoms that are evident in each individual. Such treatment may require the coordinated efforts of a team of medical professionals, such as:

  • Pediatricians or internists.
  • Doctors who diagnose and treat disorders of the skeleton, joints, muscles, and related tissues (orthopedists).
  • Surgeons
  • Physiotherapists; and / or other health professionals.

Various orthopedic techniques, including surgery, may be recommended to help treat or correct certain skeletal abnormalities associated with the disorder.

For example, as noted above, although the outward lean of the legs tends to improve during later childhood, surgical straightening may be recommended in some cases.

In women with hypochondroplasia who are pregnant, cesarean section is often necessary for delivery.

Early intervention can be important to help ensure that affected children reach their potential. Special services that may be beneficial may include special education, physical therapy, occupational therapy, and / or other medical, social, or vocational services.

Genetic counseling will be beneficial to affected individuals and their families. Another treatment for this disorder is symptomatic and supportive.