Welcome to PhenoDis

Pacman dysplasia

General Information (adopted from Orphanet):

Synonyms, Signs:	EPIPHYSEAL STIPPLING WITH OSTEOCLASTIC HYPERPLASIA Epiphyseal stippling syndrome - osteoclastic hyperplasia
Number of Symptoms	17
OrphanetNr:	1952
OMIM Id:	167220
ICD-10:	Q77.8
UMLs:	C1833676
MeSH:	C538095
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence:	< 10 cases [Orphanet]
Inheritance:	Autosomal recessive [Orphanet]
Age of onset:	Antenatal Neonatal [Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases:

Primary osteolysis
-Rare bone disease
-Rare developmental defect during embryogenesis
-Rare genetic disease

Symptom Information: Sort by abundance

	Symptom Information	Symptom	Abundance	DB Freq
1	(HPO:0000248)	Brachycephaly	Very frequent [Orphanet]	222 / 7739
2	(HPO:0000601)	Hypotelorism	Very frequent [Orphanet]	83 / 7739
3	(HPO:0002970)	Genu varum	Very frequent [Orphanet]	60 / 7739
4	(HPO:0006487)	Bowing of the long bones	Very frequent [Orphanet]	95 / 7739
5	(HPO:0003468)	Abnormality of the vertebrae	Very frequent [Orphanet]	77 / 7739
6	(HPO:0011849)	Abnormal bone ossification	Very frequent [Orphanet]	35 / 7739
7	(HPO:0005716)	Lethal skeletal dysplasia		6 / 7739
8	(HPO:0100670)	Rough bone trabeculation	Very frequent [Orphanet]	12 / 7739
9	(HPO:0010655)	Epiphyseal stippling	Very frequent [Orphanet]	32 / 7739
10	(HPO:0001643)	Patent ductus arteriosus	Very frequent [Orphanet]	228 / 7739
11	(HPO:0001939)	Abnormality of metabolism/homeostasis		328 / 7739
12	(HPO:0000006)	Autosomal dominant inheritance		2518 / 7739
13	(HPO:0011420)	Death	Very frequent [Orphanet]	184 / 7739
14	(OMIM)	Periosteal cloaking		3 / 7739
15	(OMIM)	Stippling of coccygeal and sacral vertebral region		1 / 7739
16	(OMIM)	Marrow filled with loose fibrous tissue containing numerous large multinucleated osteoclasts associated with Howship lacunae on the endosteal surface		1 / 7739
17	(OMIM)	Sagittal clefting of upper vertebrae		1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol	Variation	Clinical significance	Reference

Additional Information:

Clinical Description OMIM

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 ... 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.

Symptoms & Signs

	Field	Query
	Disease
	Symptom