1/147. chondrodysplasia punctata stemming from maternal lupus erythematosus. The finding of stippled epiphyses on a neonatal radiograph generates a wide differential diagnosis, including genetic and teratogenic causes. We report the case of a male infant with stippled epiphyses evident on neonatal radiographs in whom a typical rash of lupus erythematosus developed. The skin abnormalities in the infant resulted in a diagnosis of systemic lupus erythematosus in his mother. Over a 3-year follow-up period, the child has demonstrated strikingly short stature, midface hypoplasia, anomalous digital development, slow resolution of the stippled epiphyses, and near normal cognitive development. The differential diagnosis of chondrodysplasia punctata and the literature supporting maternal lupus as one cause are reviewed. ( info) |
2/147. Multiple epiphyseal dysplasia. A family case report. Six cases of multiple epiphyseal dysplasia were found in a 30-member kindred. The kindred showed an increased incidence of other joint abnormalities. A dominant pattern of inheritance was not confirmed. ( info) |
| The radiographic observation of stippled calcification in cartilage defines the chondrodysplasia punctata group of bone dysplasias. Several other diseases may be associated with the radiographic finding of punctate epiphyses, usually uncommonly - for example, trisomy 21. Other more subtle chromosomal abnormalities also associated with punctate epiphyses include microdeletions of the x chromosome. A case of turner syndrome with punctate calcification of the epiphyses is described. ( info) |
4/147. Late diagnosis of maternal PKU in a family segregating an arylsulfatase [corrected] E mutation causing symmetrical chondrodysplasia punctata. Mutations in the arylsulfatase E gene, located on the x chromosome, have been shown to cause chondrodysplasia punctata (CDP). A substitution of arginine with serine at amino acid 12 (R12S) was identified in a patient with typical features of mild symmetrical CDP including mild mental retardation. The proband was institutionalized and was found to have seven full and half siblings all of whom were microcephalic. Six siblings are alive and all are mentally retarded. The mother is borderline retarded. The mother and three daughters are carriers of the R12S change, but do not appear to have CDP. A son and three other daughters do not carry the R12S change. Further studies revealed that the mother had phenylketonuria (PKU) and the children maternal PKU. This suggests that the R12S change is not the primary cause of short stature, microcephaly, and mental retardation in this family. The relationship between CDP and PKU, both of which can cause short statue and mental retardation, is discussed. ( info) |
5/147. Conradi-Hunermann syndrome with ocular anomalies. We report a Japanese girl with the Conradi-Hunermann form of chondrodysplasia punctata and anterior segment malformations characteristic of Axenfeld-Rieger syndrome. The patient also had cataracts and unilateral optic atrophy. A possible role for homeobox-containing genes in the etiology of this type of chondrodysplasia punctata is suggested as an explanation for the coincidence of these two syndromes. ( info) |
6/147. Novel and recurrent EBP mutations in X-linked dominant chondrodysplasia punctata. chondrodysplasia punctata (CDP) is a heterogeneous group of skeletal dysplasias characterized by stippled epiphyses. A subtype of CDP, X-linked dominant chondrodysplasia punctata (CDPX2), known also as Conradi-Hunermann-Happle syndrome, is a rare skeletal dysplasia characterized by short stature, craniofacial defects, cataracts, ichthyosis, coarse hair, and alopecia. The cause of CDPX2 was unknown until recent identification of mutations in the gene encoding Delta(8),Delta(7) sterol isomerase emopamil-binding protein (EBP). Twelve different EBP mutations have been reported in 14 patients with CDPX2 or unclassified CDP, but with no evidence of correlation between phenotype and nature of the mutation. To characterize additional mutations and investigate possible phenotype-genotype correlation, we sequenced the entire EBP gene in 8 Japanese individuals with CDP; 5 of them presented with a CDPX2 phenotypes. We found EBP mutations in all 5 CDPX2 individuals, but none in non-CDPX2 individuals. Three of these CDPX2 individuals carried novel nonsense mutations in EBPand the other two, separate missense mutations that had been reported also in different ethnic groups. Our results, combined with previous information, suggest all EBP mutations that produce truncated proteins result in typical CDPX2, whereas the phenotypes resulted from missense mutations are not always typical for CDPX2. patients with nonsense mutations showed abnormal sterol profiles consistent with a defect in Delta(8), Delta(7) sterol isomerase. X-inactivation patterns of the patients showed no skewing, an observation that supports the assumption that inactivation of the EBP gene occurs at random in affected individuals. ( info) |
7/147. cholesterol metabolsim defect associated with Conradi-Hunerman-Happle syndrome. We present a 6-week-old black girl with Conradi-Hunerman-Happle syndrome (CHS). The mother had no past medical history of illness, and the pregnancy progressed normally to a spontaneous vaginal delivery at 36 weeks. There was no known significant family history. A diagnosis of chondrodysplasia punctata was made at birth from physical examination and X-ray findings. On physical examination at 6 weeks, a koala face, a saddle nose, and a right-sided cataract were noted (Fig. 1a,b). There was unilateral left-sided ichthyosis well demarcated at the midline, with whorled brown fine scale following Blashko's lines on the patient's right side. Orthopedic complications were bilateral but were more pronounced on the left side. There was bilateral shortening of the humerus, with polydactyly of the right hand, arachnodactyly of the left fingers, bilateral clubbing, and mild contractures of the feet. x-rays showed multiple calcifications along the spine, proximal and distal femoral epiphysis, and proximal humeral epiphysis (Fig. 2). The patient was treated with emollients (aquaphor) twice daily with continuing improvement in ichthyosis. The clubbed feet were treated with splinting and the polydactyly was corrected by surgery. ophthalmology was to follow the patient for her right-sided cataract. At the patient's 4-month follow-up, the ichthyosis showed a marked improvement with some residual hypo- pigmented atrophoderma noted. The distribution remained unchanged. Biopsies taken of ichthyotic lesions showed compact hyperkeratosis and follicular plugging. Vesicles within the stratum corneum contained amorphous material (Fig. 3a,b). The granular cell layer was thickened with retained oval nuclei. The epidermal and adnexal epithelium were disorganized. Increased apoptotic/dyskeratotic keratinocytes were seen within the epidermis, but were most evident within the follicular epithelium. Ultrastructural studies showed saccular dilations of the acellular space within the stratum corneum. These acellular spaces were filled with unprocessed lamellated pleated sheets and vesicle complexes and processed lamellae. Dyskeratotic cells were seen within the stratum spinosum. Red blood cell (RBC) plasmalogen levels and polyunsaturated fatty acids (PUFA), including decosahexaenoic acid (DHA), were within normal limits. plasma very long chain fatty acids (VLCFA), including C26 : 0/C22 : 0 ratios, phytanic and pristanic acids, plasmalogen, and phytanic/pristanic ratios, trihydroxycholestanic acid (THCA) and dihydroxycholestanoic acid (DHCA) including their ratios, THCA/cholic acid and DHCA/chenodeoxycholic acid, and PUFAs including DHA were within normal limits. urine organic acids and piecolic acid were within normal limits. Despite these normal values, there was an increase in cholest-8(9)-en-3beta-ol of 6.8 microg/mL (normal, 0.01-0.10 microg/mL) and an increase in 8-dehydrocholesterol (5.1 microg/mL) (normal, <0.10 microg/mL). ( info) |
8/147. Brachytelephalangic dwarfism due to the loss of ARSE and SHOX genes resulting from an X;Y translocation. Here we report an 8-year-old male patient who had mesomelic shortening of forearms and legs, brachytelephalangia and ichthyotic skin lesions. Chromosomal analysis showed an X;Y translocation involving the short arm of the x chromosome (Xp). fluorescence in situ hybridization (FISH) and molecular studies localized the breakpoints on Xp22.3 in the immediate vicinity of the KAL gene demonstrating deletions of steroid sulfatase (STS), arylsulfatase E (ARSE), and short stature homeo box (SHOX) genes. It was suspected that the patient was suffering from chondrodysplasia punctata because of a loss of the arylsulfatase E (ARSE) gene. However, no stippled epiphyses were to be seen in the neonatal radiograph. Interestingly, this patient is the first case with a proven loss of the ARSE gene without chondrodysplasia punctata, assuming that chondrodysplasia punctata is not an obligatory sign of ARSE gene loss. Brachytelephalangia was the only result of ARSE gene deletion in this case. The patient's mother also had dwarfism and showed Madelung deformity of the forearms. She was detected as a carrier of the same aberrant x chromosome. The male patient did not show Madelung deformity, demonstrating that Lerri-Weill syndrome phenotype may be still incomplete in children with SHOX gene deletion. The wide clinical spectrum in the male and the Leri-Weill phenotype in his mother are the results of both a deletion involving several sulfatase genes in Xp22.3 and the SHOX gene located in the pseudoautosomal region. Nevertheless, there is no explanation for the absence of chondrodysplasia punctata despite the total loss of the ARSE gene. Further studies are necessary to investigate genotype/phenotype correlation in cases with translocations or microdeletions on Xp22.3, including the ARSE and the SHOX gene loci. ( info) |
| The osteogenesis imperfecta syndromes constitute a group of heterogeneous, heritable skeletal dysplasias. Of the 4 types, type II is the most severe, with an incidence of 1 per 55,000. It is characterized by malformed bones secondary to abnormal collagen type i synthesis. Affected fetuses are divided into 3 groups: A, B, and C. All groups have long bones described as "wrinkled" or "crumpled" secondary to repeated fractures. Many bones also show evidence of demineralization, which is especially evident in the bones of the face and calvaria. In groups A and C, the chest is generally small, with thickened and shortened ribs, and each rib has characteristic "beading" patterns secondary to repeated fracturing. Sonography has traditionally been successful in the diagnosis of osteogenesis imperfecta at an early gestational age. chondrodysplasia punctata describes a heterogeneous group of skeletal disorders characterized by abnormal mineralization of bones during gestation. There are many different causes of it, but some of the specific subtypes include rhizomelic, X-linked dominant (also known as Conradi-Hunermann syndrome), X-linked recessive, and tibia-metacarpal. We report a case of severe X-linked dominant chondrodysplasia punctata, which sonographically had common features with osteogenesis imperfecta type II. ( info) |
10/147. The Upper Paleolithic triple burial of Dolni Vestonice: pathology and funerary behavior. This work focuses on paleopathological analysis of one of the skeletons from the Gravettian triple burial of Dolni Vestonice (Moravia) and addresses issues of Upper Paleolithic funerary behavior. The burial includes the well-preserved skeletons of three young individuals. The skeleton in the middle (DV 15) is pathological and very problematic to sex; the other two (DV 13 and DV 14) are males and lie in an unusual position. The young age, the possibility of a simultaneous interment, and the position of the three specimens have given rise to speculations about the symbolic significance of this spectacular and intriguing funerary pattern. The pathological condition of the skeleton in the middle further emphasizes its peculiarity. Main pathological changes of the DV 15 skeleton include: asymmetric shortening of the right femur and of left forearm bones, bowing of the right femur, right humerus, and left radius, elongation of fibulae, dysplasias of the vertebral column, and very marked enamel hypoplasias. Scrutiny of the medical literature suggests that the most likely etiology is chondrodysplasia calcificans punctata (CCP) complicated by trauma and early fractures of the upper limbs. CCP is a rare inherited disorder characterized by stippled ossification of the epiphyses. The cartilaginous stippling is a transient phenomenon that disappears during infancy, leaving permanent deformities on affected bones. Among the different forms of CCP, the X-linked dominant form is that resulting in asymmetric shortening and is lethal during early infancy in males. Thus, survival of DV 15 until young adult age would require the specimen to be a female. Clinical findings often associated with the disease (erythemas, ichthyosis, alopecia, cataracts, and joint contractures, among others) would emphasize the singular aspect of this individual, pointing to a condition that should be carefully taken into account when speculating on the significance of that peculiar burial. ( info) |