168: Hereditary Disorders of Connective Tissue

Key Points

  • Disease summary:

    • Hereditary disorders of connective tissue (HDCT) are a group of disorders in which genetic errors affect the proper formation of connective tissue, the intercellular material that holds human tissues together.

    • Connective tissue is a complex network of substances (including collagen, elastin, fibrillin, fibulin, and many others) produced by fibroblast cells. The specific combination and proportion of these elements differs from one tissue to another to create diverse mechanical properties and functions within the human body.

    • There is extensive overlap both clinically and genetically between the HDCT. A single gene can affect the connective tissue of multiple organ systems (pleiotropy). The clinical features often overlap with other connective disorders caused by mutations in different genes. Furthermore, a single gene may be linked to multiple distinct disorders based on the mutation type and genetic environment.

    • The ability to differentiate between the 40+ known HDCT has the capacity to significantly alter patient care.

  • Hereditary basis:

    • The hereditary basis of HDCT varies by disorder, and can include autosomal recessive, autosomal dominant, X-linked, and de novo mutations. Refer to Table 168-1 for syndrome- and gene-specific details.

    • Differential diagnosis: Many different clinical findings may spur consideration of an underlying HDCT. Some of the most common findings are joint laxity, skin hyper- or inelasticity, vascular aneurysms, hernias, long bone overgrowth, and ophthalmologic pathology. The differential diagnosis for a suspected HDCT is not easily summarized. The major entities and causative genes and inheritance patterns are summarized in Table 168-1.

Table 168-1   Genetic Differential Diagnosis