Progressive diaphyseal dysplasia: A three-generation family with markedly variable expressivity

Abstract

Progressive diaphyseal dysplasia was found in a 3-generation family including 18 affected individuals. We describe the clinical and radiographic manifestations in 6 of 18 patients with this autosomal-dominant bone dysplasia and the good symptomatic response to corticosteroid treatment in one of these. The variability of manifestations of the disease in this family and in others previously described seems to depend on the sex of the patient and the parental origin of the mutation. The patients with more severe symptoms are males who inherited an allele of paternal origin. We suggest that the progressive diaphyseal dysplasia gene has a function in endochondral bone formation and that its mutation is a dynamic one with repeat expansion enhanced in father-to-son transmission.

Anticipation in progressive diaphyseal dysplasia

“…A previous suggestion that anticipation was enhanced in father to son transmission2 is not supported by these new data; the patient with the earliest age of onset and one of the most severely affected is a female (IV.12, fig 1, table 1), who inherited the disease from her mother.…”

“…We have recently described a patient with this diagnosis and suggested the presence of anticipation,2 the tendency of a familial disorder to occur earlier in the younger than in the older generations of a family 3…”

Phenotypic variability at the TGF-β1 locus in Camurati-Engelmann disease

“…Families were of Portuguese (family 1), French (family 2, 4, 6, 7), Belgian (family 3) and Australian (family 5) origin. Table 1 summarizes the clinical and radiological manifestations of the disease (family 1 has been previously described in detail by Saraiva 1997Saraiva , 2000. All affected individuals disclosed X-ray manifestations of diaphyseal dysplasia but a broad intrafamilial variability was noted.…”

Hearing loss in Camurati Engelmann disease: a case report

“…It is characterized by progressive expansion and sclerosis, affecting mainly the diaphyses of the long bones. Pelvic bones, skull, mandible, and vertebrae are also thickened [9][10][11][12][13][14][15] . CED typically presents in childhood with generalized muscle weakness, lower limb pain, and a waddling gait 5 .…”