86 Pyknodysostosis
Pyknodysostosis 845
PKND, Osteopetrosis acro-osteolytica
Short stature, frontal prominence, small face, pinched/
anteverted nose, prominent eyes, short terminal pha- langes, dental anomalies, increased bone fragility Frequency: Rare.
Genetics
Autosomal recessive (OMIM 265800), caused by mutations in the CSTK gene encoding cathepsin K, a lysosomal cysteine protease expressed in osteoclasts, whose deficiency results in defective degradation of bone matrix proteins; disease gene locus mapped to 1q21.
Clinical Features
• Short stature (adult height 135–150 cm)
• Wide cranial sutures, frontal prominence
• Midface hypoplasia, pinched nose, anteverted nares
• Prominent eyes, blue sclerae
• Delayed teeth eruption, persistence of deciduous teeth
• Micrognathia, pointed chin
• Mildly short limbs, genua valga
• Wrinkled skin of hands, short terminal phalanges
• Narrow shoulders, narrow grooved chest
• Respiratory distress, hyperventilation, tendency to vomiting and aspiration
• Kyphosis, scoliosis, lumbar lordosis
• Hip dislocation
• Increased bone fragility Differential Diagnosis
• Cleidocranial dysplasia
• Craniomandibular dermatodysostosis
• Osteopetrosis and other dense bone disorders
Radiographic Features Generalized Bone Defects
• Generalized osteosclerosis with moderate meta- physeal undermodeling of long bones
• Fragile bones, multiple stress fractures Skull
• Dolichocephaly, with frontal and occipital bossing
• Wide open sutures and fontanels (especially the parieto-occipital), multiple wormian bones
• Sclerosis of skull base and cranial vault, dense orbital rims, absent convolutional markings
• Underdeveloped or absent sinuses and mastoid cells
• Maxillary hypoplasia, relative mandibular prog- nathism, obtuse angle of mandible
• Ectopic teeth, enamel hypoplasia Chest
• Resorption of acromial ends of clavicles
• Narrowed thorax Extremities
• Resorption of distal phalanges of fingers and toes (acro-osteolysis), progressive with age
• Moderate metaphyseal flaring
• Mild bowing of tibias Pelvis
• Hypoplastic supra-acetabular regions relative to the iliac crests
• Coxa valga Spine
• Spondylolysis (L4–5) and spondylolisthesis
• Sclerotic vertebrae
• Errors of vertebral segmentation (not mandatory, mainly in cervical spine)
P P
Fig. 86.1. Patient 1, at 12 years. Frontal prominence, midface hypoplasia, pinched nose, and micrognathia. (Reprinted, with permission, from Mastroiacovo et al. 1990)
Bibliography
Edelson JG, Obad S, Geiger R, On A, Artul HJ. Pycnodysostosis:
orthopedic aspects with a description of 14 new cases. Clin Orthop 1992; 280: 263–76
Elmore SM. Pycnodysostosis: a review. J Bone Joint Surg Am 1967; 49: 153–63
Gelb BD, Edelson JG, Desnick RJ. Linkage of pycnodysostosis to chromosome 1q21 by homozygosity mapping. Nat Genet 1995; 10: 235–7
Gelb BD, Shi GP, Chapman HA, Desnick RJ. Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency. Sci- ence 1996; 273: 1236–8
Gelb BD, Willner JP, Dunn TM, Kardon NB,Verloes A, Poncin J, Desnick RJ. Paternal uniparental disomy for chromosome 1 revealed by molecular analysis of a patient with pycn- odysostosis. Am J Hum Genet 1998; 62: 848–54
Mills KLG, Johnston AW. Pycnodysostosis. J Med Genet 1988;
25: 550–3
Maroteaux P. Toulouse-Lautrec’s diagnosis. Nat Genet 1995; 11:
362–3
Mastroiacovo P, Dallapiccola B,Andria G, Camera G, Lungarot- ti MS. Difetti congeniti e sindromi malformative. McGraw- Hill, Milan, 1990
Pyknodysostosis 846
Fig. 86.2 a, b. Patient 2, at 7 years. Note moderate sclerosis of the calvarium and skull base, frontal bossing, wide open cra- nial fontanels and sutures with wormian bones, relative
hypoplasia of the facial bones with underdeveloped paranasal sinuses, and markedly flattened mandibular angle
a b
Fig. 86.3 a, b. Patient 2, at 7 years. Slightly increased vertebral bone density, mild lumbar scoliosis, and spondylolysis with spondylolisthesis at L4–5
a b
Pyknodysostosis 847
P P
Fig. 86.4. Patient 2, at 9 years. Note lateral hypoplasia of clavi- cle and moderate sclerosis of ribs, scapula, and proximal humerus
Fig. 86.5. Patient 2, at 9 months.
Note hypoplasia of the supra-ac- etabular portions of iliac bones compared with iliac crests, in- creased acetabular angle, and mild bone sclerosis
Fig. 86.6. Patient 3, newborn.
Mild thickening of cortices of long bones, and moderate meta- physeal flaring. Tibial shaft is slightly bowed. (Courtesy of Dr.
S. Fasanelli, Rome, Italy)
Pyknodysostosis 848
Fig. 86.7 a–c. Patient 2, at a 2 years, b 7 years, and c 15 years. The hand is short and stubby, becoming increasingly dense with advancing age. Note bone resorption of some of the distal phalanges, and the dynamic nature of such lesions (regressing in left 1st and 2nd fingers from a to b and progressing in right 1st finger from b to c). Also note bulbous appearance of proximal ends of metacarpals 2 through 5
a
c
b
Fig. 86.8. Patient 2, at 7 years.
Note lytic lesions of distal pha- langes, cone-shaped proximal phalanges, and sclerosis of short tubular bones
