Hypochondrogenesis is a severe

genetic disorder A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosome abnormality. Although polygenic disorders ...

causing malformations of

bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...

growth. The condition is characterized by a short body and limbs and abnormal bone formation in the

spine Spine or spinal may refer to: Science Biology * Spinal column, also known as the backbone * Dendritic spine, a small membranous protrusion from a neuron's dendrite * Thorns, spines, and prickles, needle-like structures in plants * Spine (zoology), ...

and

pelvis The pelvis (: pelves or pelvises) is the lower part of an Anatomy, anatomical Trunk (anatomy), trunk, between the human abdomen, abdomen and the thighs (sometimes also called pelvic region), together with its embedded skeleton (sometimes also c ...

. Hypochondrogenesis is a subtype of

collagenopathy, types II and XI The type II and XI collagenopathies are a group of disorders that affect connective tissue, the tissue that supports the body's joints and organs. These disorders are caused by defects in type II or type XI collagen. Collagens are complex molecules ...

, and is similar to another skeletal disorder, achondrogenesis type 2, although the spinal changes seen in hypochondrogenesis tend to be somewhat milder.

Signs and symptoms

Symptoms of hypochondrogenesis include:

edema Edema (American English), also spelled oedema (British English), and also known as fluid retention, swelling, dropsy and hydropsy, is the build-up of fluid in the body's tissue (biology), tissue. Most commonly, the legs or arms are affected. S ...

, limb undergrowth,

spondyloepiphyseal dysplasia Spondyloepiphyseal dysplasia congenita (abbreviated to SED more often than SDC) is a rare disorder of bone growth that results in dwarfism, characteristic skeletal abnormalities, and, in some instances, problems with Visual perception, vision and ...

short ribs Short ribs are a cut of beef taken from the brisket, chuck, plate, or rib areas of beef cattle. They consist of a short portion of the rib bone and the surrounding meat, which varies in thickness. There are two major types of cuts: the "flanke ...

respiratory failure Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide, or both cannot be kept at normal levels. A drop in the oxygen carried in the blood is known as hypoxemia; a r ...

, short chin, upper limb undergrowth, thoracic hypoplasia,

hypertelorism Hypertelorism is an abnormally increased distance between two organs or bodily parts, usually referring to an increased distance between the orbits (eyes), or orbital hypertelorism. In this condition, the distance between the inner eye corners, a ...

hydrops fetalis Hydrops fetalis or hydrops foetalis is a condition in the fetus characterized by an accumulation of fluid, or edema, in at least two fetal compartments. By comparison, hydrops allantois or hydrops amnion is an accumulation of excessive fluid in ...

pulmonary hypoplasia Pulmonary hypoplasia is an incomplete development of the lungs, resulting in an abnormally low number or small size of bronchopulmonary segments or alveoli. A congenital malformation, most often occurs secondary to other fetal abnormalities tha ...

, and a

cleft palate A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nose. The ...

Pathophysiology

Hypochondrogenesis is one of the most severe conditions in a spectrum of disorders caused by mutations in the ''

COL2A1 Collagen, type II, alpha 1 (primary osteoarthritis, spondyloepiphyseal dysplasia, congenital), also known as COL2A1, is a human gene that provides instructions for the production of the pro-alpha1(II) chain of type II collagen. Gene The COL2A1 ...

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. The protein made by this gene forms type II collagen, a molecule found mostly in

cartilage Cartilage is a resilient and smooth type of connective tissue. Semi-transparent and non-porous, it is usually covered by a tough and fibrous membrane called perichondrium. In tetrapods, it covers and protects the ends of long bones at the joints ...

and in the clear gel that fills the eyeball (the vitreous). Type II collagen is essential for the normal development of bones and other connective tissues (tissues that form the body's supportive framework). Mutations in the ''

'' gene interfere with the assembly of type II collagen molecules, which prevents bones from developing properly. This condition is caused by new mutations in the COL2A1 gene. Hypochondrogenesis is considered an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

disorder because the affected gene is located on an

autosome An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosomal (sex chromosome) pairs, which may have different structures. The DNA in autosomes ...

, and only one copy of the altered gene is necessary to cause the condition. The disorder is not passed on to the next generation, however, because affected individuals do not live long enough to have children.

Diagnosis

Affected infants have short arms and legs, a small chest with short ribs, and underdeveloped

lung The lungs are the primary Organ (biology), organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the Vertebral column, backbone on either side of the heart. Their ...

s. The spinal bones (

vertebrae Each vertebra (: vertebrae) is an irregular bone with a complex structure composed of bone and some hyaline cartilage, that make up the vertebral column or spine, of vertebrates. The proportions of the vertebrae differ according to their spinal ...

) in the neck and part of the pelvis (the sacrum) do not harden, or

ossify Ossification (also called osteogenesis or bone mineralization) in bone remodeling is the process of laying down new bone material by cells named osteoblasts. It is synonymous with bone tissue formation. There are two processes resulting in the ...

, properly. The face appears flat and oval-shaped, with widely spaced eyes, a small chin, and, in some cases, an opening in the roof of the mouth called a

. The abdomen is enlarged, and excess fluid may build up in the body before birth (a condition called

). As a result of these serious health problems, infants are usually premature and stillborn or die shortly after birth from respiratory failure. Some infants have lived for a time, however, with intensive medical support. Babies who live past the newborn period are usually reclassified as having spondyloepiphyseal dysplasia congenita, a related disorder on the spectrum of abnormal bone growth.

Treatment

There is no cure or treatment for hypochondrogenesis.

References

External links

''This article incorporates public domain text fro
The U.S. National Library of Medicine
' {{Scleroprotein disease Collagen disease