Pycnodysostosis: Natural history and management guidelines from 27 French cases and a literature review

Abstract

Pycnodysostosis is a lysosomal autosomal recessive skeletal dysplasia characterized by osteosclerosis, short stature, acro‐osteolysis, facial features and an increased risk of fractures. The clinical heterogeneity of the disease and its rarity make it difficult to provide patients an accurate prognosis, as well as appropriate care and follow‐up. French physicians from the OSCAR network have been asked to fill out questionnaires collecting molecular and clinical data for 27 patients issued from 17 unrelated families. All patients showed short stature (mean = −3.5 SD) which was more severe in females (P = .006). The mean fracture rate was moderate (0.21 per year), with four fractures in total average. About 75% underwent at least one surgery, with an average number of 2.1 interventions per patient. About 50% required non‐invasive assisted ventilation due to sleep apnea (67%). About 29% showed psychomotor difficulties and 33% needed a school assistant or adapted schooling. No patient had any psychological evaluation or follow‐up. Molecular data were available for 14 families. Growth hormone administration was efficient on linear growth in 40% of cases. We propose several axis of management, such as systematic cerebral MRI for Chiari malformation screening at diagnosis and regular psychological follow‐up.

Cathepsins in the Pathophysiology of Mucopolysaccharidoses: New Perspectives for Therapy

“…Pycnodysostosis does not correlate with increased mortality; however, it can cause significant morbidity such as recurrent fractures, osteolysis of the distal phalanges, craniosynostosis, respiratory sleep disorders, short stature, and dental problems [43]. To date, no therapy is effective for the cure of PKND, although growth hormone treatment has been shown to improve growth rates and final heights in patients with PKND [149]. Targeted enzyme or gene replacement therapies are being investigated for the cure of PKND [43].…”

Pyknodysostosis (Osteopetrosis Acro-Osteolytica)

“…While PKND was first described in 1962 (6,7), it remains an exceedingly rare diagnosis until recently (3,8,9). Differential diagnoses include fluorosis, malignancy, myelosclerosis, other forms of osteopetrosis, Pagets disease, and acromegaly.…”

“…Three hallmark features of PKND are disproportional short stature, osteosclerosis, and acro-osteolysis. While it is difficult to define a classic presentation of PKND given the heterogeneity of clinical features, recent case series have shed light on the more common features of the disease which can inform clinical decision making and diagnostic workup (8,9).…”

“…The disorder presents with an array of other skeletal complications beyond osteosclerosis. Acro-osteolysis is the second most common skeletal complication present at the time of diagnosis in the vast majority of cases (9). The high prevalence of this relatively unique radiographic finding in patients with PKND underscores the importance of a thorough radiographic workup in patients with features of sclerosing bone disorders.…”

“…In the absence of familiarity with the disorder, other bony abnormalities recognized on plain radiographs can lead the clinician to diagnosis. These features include open fontanels, delayed fusing of skull sutures, wormian bones, craniostenosis, and hypo-pneumatized or non-pneumatized mastoids or paranasal sinuses (9,11).…”