Abstract:
Organizations such as the European Medicines Agency and the U. S. Food and Drug Administration define orphan diseases mainly based on prevalence of diagnosed cases and the severity of the classic phenotype. Rare or Orphan disease, is a common term in practice, rare disease is only applied to the severe recognizable syndrome (which in fact rare), but the mild and moderate types are so frequent. Rare disease manifests itself mostly soon after birth. But the mild and moderate showed up the abnormalities later in life. Physicians frequently use the term rare, or idiopathic because these are the easiest terms to apply. The mild and the moderate types of genetic disorders are the real risk in orthopedic practices and in other medical disciplines.
Because they manifest the health problem late in life, the gene hides itself for a decade or more. Then, suddenly, it showed up with a partial but serious skeletal or extra-skeletal abnormality.
Etiology understanding is crucial for a successful management. Variable expressivity and incomplete penetrance. Many inherited disorders show: Variable expressivity i.e severity varies widely among relatives. Incomplete penetrance i.e some carriers have minimal or no symptoms. This means that within one family you may see: One person with a severe “rare disease” phenotype but siblings, relatives are with mild or moderate manifestations. Family histories are often not collected in enough depth. Mild symptoms in relatives may be considered coincidental rather than part of a shared inherited condition. In my current presentation, highlighting three-generational family study in which 13 family subjects showed variable disorders (mild-moderate clinical disorders). Whereas two siblings out of 13 family subjects showed the severe form of the disease.
