Alternative titles; symbols
SNOMEDCT: 722127006; ORPHA: 1952;
Shohat et al. (1993) described a preterm (28 weeks) female fetus with a 'new' lethal skeletal dysplasia characterized by distinctive epiphyseal stippling, periosteal cloaking, and unusual microscopic morphology. Radiologically there was marked stippling of the coccygeal and sacral vertebral region as well as of the epiphyses. Long bones showed wide periosteal cloaking and bowing. Sagittal clefting was present in the upper spine. In contrast to the normal morphology of the epiphyses and growth plates, the marrow was filled with loose fibrous tissue containing numerous large multinucleated osteoclasts which were associated with Howship lacunae on the endosteal surface. The morphologic features were consistent with elevated bone resorption. Shohat et al. (1993) suggested the pseudo-eponym 'Pacman dysplasia,' based on the video game in which little round creatures actively 'eat dots.'
Wilcox et al. (1998) reported 2 sib fetuses with radiologic and morphologic findings similar to those of Pacman dysplasia. The male and female fetuses were electively terminated at 20 and 16 weeks, respectively, after routine ultrasound studies showed short-limbed dwarfism. The radiographic appearance was characterized by undermineralized bone, stippling, rhizomelic and mesomelic shortness, platyspondyly, and a short, broad pelvis. The metaphyses were dense, but the diaphyseal cortices were thin with undermodeled long bones, and there was a deficient trabecular pattern suggesting marrow replacement. Chondroosseous structure was characterized by deficient trabecular bone formation, a fibrous marrow, and numerous large, multinucleated osteoclasts lining the endosteal surfaces of the metaphyseal bone.
Miller et al. (2003) reported a male fetus of a pregnancy electively terminated at 24 weeks due to suspected skeletal dysplasia. Postmortem radiography showed 'nearly identical' features to the original case of Pacman dysplasia (Shohat et al., 1993) with shortening of long bones, mild to moderate femoral bowing, dramatic epiphyseal, tarsal, and spinal puncta, vertebral clefting and platyspondyly, phalangeal shortening, osteopenia, periosteal cloaking about long bones, and metaphyseal lucent bands. Saul et al. (2005) described a female sib of the fetus reported by Miller et al. (2003). She had a clinical course and biochemical, cytologic, and radiographic features consistent with the diagnosis of mucolipidosis type II (ML II; 252500). Saul et al. (2005) suggested that what is called Pacman dysplasia may represent a prenatal manifestation of ML II.
Wilcox et al. (2005) stated that Pacman dysplasia is distinct from ML II, noting that enzymatic analysis of cultured fibroblasts from one of the sibs reported by Wilcox et al. (1998) revealed normal activities, thus excluding ML II. Wilcox et al. (2005) commented that radiographic and morphologic criteria cannot be used to distinguish between the disorders; for a definitive diagnosis, pathologic material must be examined for lysosomal storage or enzyme assays must be performed.
Wilcox et al. (2005) suggested that Pacman dysplasia is an autosomal recessive disorder.
Feingold (2006) and Saul et al. (2006) discussed the need for a more appropriate and precise term for this syndrome, perhaps based on the histology or biochemistry of the disorder.
Feingold, M. The use of inappropriate, demeaning, and pejorative terminology to describe syndromes. (Letter) Am. J. Med. Genet. 140A: 410-411, 2006. [PubMed: 16419131] [Full Text: https://doi.org/10.1002/ajmg.a.31108]
Miller, S. F., Proud, V. K., Werner, A. L., Field, F. M., Wilcox, W. F., Lachman, R. S., Rimoin, D. L. Pacman dysplasia: a lethal skeletal dysplasia with variable radiographic features. Pediat. Radiol. 33: 256-260, 2003. [PubMed: 12709756] [Full Text: https://doi.org/10.1007/s00247-002-0859-4]
Saul, R. A., Proud, V., Taylor, H. A., Leroy, J. G., Spranger, J. Prenatal mucolipidosis type II (I-cell disease) can present as Pacman dysplasia. Am. J. Med. Genet. 135A: 328-332, 2005. [PubMed: 15887289] [Full Text: https://doi.org/10.1002/ajmg.a.30716]
Saul, R. A., Taylor, H. A., Leroy, J., Spranger, J., Proud, V. Response to Feingold. (Letter) Am. J. Med. Genet. 140A: 412 only, 2006.
Shohat, M., Rimoin, D. L., Gruber, H. E., Lachman, R. New epiphyseal stippling syndrome with osteoclastic hyperplasia. Am. J. Med. Genet. 45: 558-561, 1993. [PubMed: 8456823] [Full Text: https://doi.org/10.1002/ajmg.1320450506]
Wilcox, W. R., Lachman, R. S., Rimoin, D. L., Wenger, D. A. Distinguishing Pacman dysplasia from mucolipidosis II: comment on Saul et al. [2005]. Am. J. Med. Genet. 135A: 333 only, 2005. [PubMed: 15887286] [Full Text: https://doi.org/10.1002/ajmg.a.30717]
Wilcox, W. R., Lucas, B. C., Loebel, B., Bachman, R. P., Lachman, R. S., Rimoin, D. L. Pacman dysplasia: report of two affected sibs. Am. J. Med. Genet. 77: 272-276, 1998. [PubMed: 9600734]