SNP Shot: Genomic Insights

Fibrochondrogenesis is a very serious skeletal dysplasia that severely impacts bone development. Infants born with this condition typically have a significantly underdeveloped chest cavity, hindering proper lung function. Consequently, the majority of infants with fibrochondrogenesis are either stillborn or succumb to respiratory failure soon after birth. However, there are instances of individuals surviving into childhood.

Hallmarks of fibrochondrogenesis include dwarfism and various skeletal malformations. Individuals affected by this condition exhibit shortened long bones in their limbs, characterized by unusual widening at the ends, often described as dumbbell-shaped. Other skeletal features include a constricted chest with short, broad ribs, and a pronounced abdomen. The vertebrae are flattened (platyspondyly) and have a distinctive pinched or pear-like appearance visible on X-rays. Further skeletal abnormalities associated with fibrochondrogenesis may encompass atypical spinal curvature and underdeveloped pelvic bones.

Individuals with fibrochondrogenesis often present with characteristic facial features. These include prominent eyes, ears positioned lower than normal, a small mouth accompanied by an elongated upper lip, and a receding chin (micrognathia). The midface tends to appear flattened, particularly with a small nose, a flat nasal bridge, and nostrils that point forward instead of downward (anteverted nares). Visual impairments, such as severe nearsightedness (high myopia) and clouding of the eye's lens (cataracts), are frequently observed in those who survive infancy. Furthermore, most affected individuals experience sensorineural hearing loss resulting from inner ear abnormalities.

Inheritance:

Generally, fibrochondrogenesis follows an autosomal recessive inheritance pattern. This means that for the condition to manifest, an individual must inherit a mutated copy of the responsible gene from both parents. These parents, while carrying one copy of the mutated gene each, typically do not exhibit symptoms of the condition. In rare cases, parents of affected children have presented with mild features possibly linked to fibrochondrogenesis, such as slightly short stature, myopia, cataracts, joint pain, and hearing loss. In at least one reported case of fibrochondrogenesis due to a COL11A2 gene mutation, the condition was inherited in an autosomal dominant manner. This means that only one copy of the altered gene is needed to cause the disorder. In this specific case, the mutation was a spontaneous (de novo) occurrence during the formation of reproductive cells (eggs or sperm) in one of the parents. Notably, there was no previous family history of the disorder.