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This article reviews the newly described biochemical (type I and II collagen) abnormalities and specific gene defects in the skeletal dysplasias. The model of the collagen molecule is described and how collagen is processed from procollagen, where and how abnormalities occur, and the types of abnormalities produced (quantitative and qualitative). The only known type I collagen defects producing skeletal dysplasias - osteogenesis imperfecta, as well as the ‘family’ of established type II collagen disorders - achondrogenesis type II, hypochondrogenesis and spondyloepiphyseal dysplasia congenita are discussed. Finally, using case presentations, the practical approach to these disorders is shown. The importance of these investigations and the subsequent reevaluation of the clinical and radiological findings of specifically delineated skeletal dysplasias are discussed.

Hallermann-Streiff syndrome (HSS) is a rare disorder with an associated constellation of radiological findings that may aid in the diagnosis of affected individuals. We reviewed the skeletal surveys of 5 affected individuals and noted some characteristic and constant findings. Radiological findings can include a large, poorly ossified skull with decreased ossification in the sutural areas. There was an increase in the number of Wormian bones. Severe mid-facial hypoplasia was present along with a prominent nasal bone. The skull films also showed an abnormally obtuse or nearly straight gonial angle. The teeth appeared small. The long bones were thin and gracile in appearance and often showed poor demarcation of the cortex from the medullary portion. Abnormal bowing of the radius and ulna was seen neonatally in 2 cases. There was widening at the metaphyseal ends of the long bones. The ribs were thin, but normal in length. The vertebral bodies were noted to be small and 3 cases had platyspondyly. There was a decreased number of sternal ossification enters. The metacarpals were also thin and gracile in appearance with metaphyseal widening. We conclude that these characteristic radiological findings in the newborn with HSS can aid in the diagnosis, and a skeletal survey in suspected individuals may be valuable in confirming the diagnosis.

We report on 6 patients with short stature and progressive enchondromatous-like changes of the vertebral bodies and the metaphyses of the long bones. Parental consanguinity was observed in 5 of 6 cases, supporting autosomal recessive inheritance. In spite of the similarity in radiographic changes and body proportions, genetic heterogeneity is suggested by the presence of CNS calcifications in 3 patients. Two of the latter had progressive quadriparesis. We tentatively classified these patients into 2 provisional types. An iliac crest biopsy in one of the patients with "type I" disease did not demonstrate enchondromatosis. Light and transmission electron microscopic studies demonstrated large cisterns and small inclusion bodies containing a flocculent material within the rough endoplasmic reticulum of the chondrocytes. Based on the histological and radiographic findings, we propose to classify these conditions among the spondylometaphyseal skeletal dysplasias.

We present 5 cases of a short-limb dwarfism syndrome whose manifestations overlap those of atelosteogenesis and oto-palato-digital syndrome Type II. Clinical, radiographic, genetic, and histologic data are presented which demonstrate differences between our patients and previously reported cases of these other conditions. We conclude that the disorder seen in these children represents a distinct chondrodysplasia for which we propose the name atelosteogenesis Type III.

The Shwachman–Bodian–Diamond syndrome (SBDS) gene is a causative gene for Shwachman–Diamond syndrome, an autosomal recessive disorder with exocrine pancreatic insufficiency, bone marrow dysfunction and skeletal dysplasia. We report here on two patients with skeletal manifestations at the severest end of the phenotypic spectrum of SBDS mutations. An 11‐year‐old Japanese girl presented with neonatal respiratory failure necessitating lifelong ventilation support, severe short stature and severe developmental delay. She developed neutropenia in infancy, and decreased serum amylase was noted in childhood. A British boy was a stillbirth with pulmonary hypoplasia and hepatic fibrosis found on autopsy. Both cases had neonatal skeletal manifestations that included platyspondyly, lacy iliac crests and severe metaphysial dysplasia, and thus did not fall in the range of the known Shwachman–Diamond syndrome skeletal phenotype but resembled spondylometaphysial dysplasia (SMD) Sedaghatian type. The girl harboured a recurrent mutation (183TA→CT) and a novel missense mutation (79T→C), whereas the boy carried two recurrent mutations (183TA→CT and 258+2T→C). We also examined SBDS in one typical case with SMD Sedaghantian type and eight additional cases with neonatal SMD, but failed to discover SBDS mutations. Our experience expands the phenotypic spectrum of SBDS mutations, which, at its severest end, results in severe neonatal SMD.

Desbuquois dysplasia is a rare form of short limb dwarfism with autosomal recessive inheritance characterized by severe short stature of prenatal onset, joint laxity, facial dysmorphic features, spur-like projections of the proximal femora (“Swedish key” or “monkey wrench”), mild vertebral and epiphyseal abnormalities, and advanced carpal and tarsal bone age. Cases may be divided into two groups depending on whether or not typical hand abnormalities are present, which include an extra ossification center distal to the second metacarpal and/or a delta phalanx of the thumb. A recent genome-wide search in four inbred Desbuquois families with typical hand abnormalities demonstrated linkage to chromosome 17q25.3. Exclusion of the 17q25.3 locus in the clinical subtype of Desbuquois dysplasia without typical hand anomalies in three inbred families was subsequently reported. We report a new family of at least four siblings and one first cousin affected with a lethal Desbuquois-like dysplasia with typical hand abnormalities. Further genomic analysis excludes linkage to chromosome 17q25.3 in this family.

Autosomal recessive infantile osteopetrosis (ARIO) is a rare and potentially fatal disorder of bone metabolism caused by a defect in osteoclast function. The pathologic features are secondary to insufficient bone resorption and usually present in the infancy. Symptoms include sclerotic bones leading to bone marrow compromise with resultant pancytopenia, cranial nerve impingement, hydrocephalus, and fracture. This is an autosomal recessive disorder caused by mutations in either TCIRG1, CLCN7, or OSTM1. Malformations are not a part of this disorder. We present a 6-month-old male, the first child between nonconsanguineous parents, who was referred to our clinic for limb defects. Findings prompting the referral included congenital left upper limb anomalies of syndactyly and radial-ulnar synostosis. There was an ipsilateral anterior rib defect, though there was no clinically appreciable hypoplasia of the pectoralis major. He also had a left low-lying, cross-fused kidney. Besides the limb anomalies, the patient presented in our clinic having signs of hydrocephalus. He had left facial nerve palsy and oculomotor abnormalities. The diagnosis of ARIO was made after hospitalization; radiographs demonstrated characteristic findings of diffuse osteosclerosis and periosteal thickening in all bones. The patient had surgical management for noncommunicating hydrocephalus with good results. The majority of cases with ARIO are compound heterozygotes. Reported homozygous patients most commonly result from a consanguineous mating or come from an isolated population (Costa Rica). Genetic testing of this patient revealed homozygosity for a rare mutation in TCIRG1, a subunit of the osteoclast vacuolar proton pump. Because this child was a product of a nonconsanguineous union, this was an unexpected result. To explain the malformations in this case, we postulated either uniparental disomy or a spontaneous contiguous gene deletion on one chromosome that included the TCIRG1 gene, which then unmasked a hemizygous recessive state. Subsequent sequence analysis of both parents for TCIRG1 mutations showed that each was a heterozygous carrier of their son9s mutation. The presence of the limb and kidney anomalies complicated the diagnosis in this case. No other reported patients with ARIO have had similar birth defects. Without treatment, early demise secondary to bone marrow failure is predicted in nearly all cases. Associated features, natural history, and management recommendations for ARIO will be reviewed.

We report four cases of a Spondyloepimetaphyseal dysplasia (SEMD) characterized by joint laxity and large joint dislocations, especially hips and knees. This condition was first reported as a distinct entity by Hall et al., (J Med Genet 1998; 35:566-572). They described three apparently sporadic patients. We present four unrelated patients (three males and one female) with similar radiogiaphic and clinical findings. Usually, this disorder is manifest in the neonatal period by joint dislocations but normal birth length. The children go on to have significant short stature by the time they are toddlers, as well as scoliosis and progressive joint deformities. They have normal psychomotor development. Three of our four patients also had laryngo/tracheomalacia. The radiographic findings include small irregular epiphyses and metaphyseal abnormalities of the long bones. The changes seen on hand x-rays are unique to this form of SEMD and consist of the characteristic finding of gracile metacarpals and the frequent finding of distal ulnar hypoplasia. As the radiographic findings overlapped somewhat with a severe form of multiple epiphyseal dysplasia (MED), mutation detection was undertaken in one proband. This child had normal sequence of previously established MED loci (COMP, exon 3 of COL9A2, exon 3 of COL9A3) as well as exons 8, 9, and, 10 of COL9A1 and COL2A1. Histology of a cartilage sample on this patient was mildly abnormal but not diagnostic. These four cases aid in confirming that SEMD with multiple joint dislocations is a discrete entity which is most likely inherited as an autosomal dominant trait.

Scapuloiliac dysostosis (also known as Kosenow syndrome, Pelvis-Shoulder Dysplasia)(MIM 169550) is a rare skeletal dysplasia which usually demonstrates extreme hypoplasia of the scapulae and ilia. The clavicles are also often affected (hypoplastic or elongated). Other radiological findings which have been reported include: lordosis of the lumbosacral spine, rounded appearance of the vertebral bodies (in infancy), rib anomalies and overconstriction of the femora. Dysmorphic features can include eye and ear abnormalities. We present two unrelated patients with Scapuloiliac Dysostosis, each of whom has additional abnormalities not previously reported in the literature. Patient #1 was an adult female with primary amenhorrea, features of Turner syndrome and a normal female karyotype. She also had partial hearing loss and hydronephrosis. In addition to her hypoplastic scapulae and ilia, she had lumbar lordosis and severe spinal dysraphism in the (lower lumbar) sacral region. The femoral heads were small with severe coxa vara. Patient #2 was a stillborn male with multiple skeletal abnormalities and malformations. Clinically, he had microphthalmia, short palpebral fissures, ambiguous genitalia and clubbed feet. Chromosomes were normal male. Radiologically, apart from the hypoplastic scapulae and ilia, he had a bell-shaped chest with thin ribs. There were radial head dislocations of the elbows, bilaterally. The proximal femoral area did not articulate with any ossified structure and the fibulae were absent. Kosenow syndrome seems to represent a spectrum of disorders including patients with only pelvic involvement to patients with multiple malformations in addition to the hypoplastic scapulae and ilia. This entity appears to exhibit genetic heterogeneity, as both autosomal dominant and recessive inheritance have been suggested.

Dysplasie epiphysaire hemimelique de la cheville gauche avec fragment osseux provenant probablement de l'astragale

We report on two male infants with a lethal skeletal dysplasia characterized by cleft palate, midface hypoplasia, downward-slanting palpebral fissures, small thorax, and bowed limbs with absent fibulae. The clinical and radiographic changes are similar to those seen in the recently proposed oto-palato-digital syndrome, type II [Fitch et al, 1983]. The disorder is X-linked with heterozygous females being more mildly affected.

The clinical and radiographic observations in eight patients, radiographs on an additional six patients, and morphologic observations on chondro-osseous tissue from two of these 14 patients form the basis for delineating an entity distinct from the heterogeneous group of skeletal dysplasia involving spine and tubular bones, the spondyloepiphyseal, and spondylometaphyseal dysplasias. Disproportionately short limbs and delayed epiphyseal maturation are present at birth, and the entity is radiographically indistinguishable from spondyloepiphyseal dysplasia (SED) congenita during infancy. The metaphyseal change that allows identification of the entity described here develops during early childhood, and radiographically is seen as "dappling," ie, the mottled appearance of alternating zones of osteosclerosis and osteopenia. Severe scoliosis and cord compression may be important clinical problems related to the spine changes in adulthood. We have identified one family with two affected sibs and normal parents, suggesting autosomal recessive inheritance and distinguishing the entity from SED congenita that has autosomal dominant inheritance.

We report on a syndrome of widow's peak, ptosis, skeletal abnormalities and other minor anomalies in a large family. The condition appears to be inherited in an X-linked dominant fashion. No similar cases have been found in the literature, suggesting that this is a "new" syndrome. Study of 5 generations of the family documents information on the natural history of the condition.

The frequency of triploid conceptuses in man is estimated to be approximately 1%; most are aborted during the first trimester. There are reports of 31 triploid fetuses which survived past the 24th week of gestation, including several infants born at term. We are unaware of a report of the prenatal diagnosis of triploidy. A typical clinical syndrome has been delineated in nonmosaic triploid fetuses and infants, including intrauterine growth retardation, syndactyly, eye and ear abnormalities, hypogonadism in males, and hydatidiform placenta. A 32-year-old primigravida presented with small uterine size at 16 weeks gestation. Subsequently the uterus grew very slowly. Ultrasound examination at 23 weeks revealed a fetal head size consistent with 20 weeks gestation and a thoracic diameter consistent with 14 weeks. Amniocentesis was done for karyotype analysis and α-fetoprotein determination. Amniography showed a small fetus with obvious disproportion between head and trunk. Abortion was induced with prostaglandin. The fetus had features consistent with the triploidy syndrome, and the amniotic fluid cells were later found to have a 69,XXY karyotype. Chromosomal polymorphisms of the fetus and parents indicated that the supernumerary haploid set of chromosomes originated from failure of the second meiotic division in the mother. This case illustrates the way in which the combined use of amniocentesis, ultrasonography, and radiographic techniques can be advantageous in prenatal diagnosis and genetic counseling, especially when the patient is relatively late in pregnancy so that it is necessary to obtain a rapid diagnosis.

Two sibs, one girl and one boy, were observed in infancy with a severe lethal skeletal dysplasia syndrome that radiologically and histologically resembled Kniest dysplasia but clearly differed in clinical course and inheritance. Kniest dysplasia is a nonlethal syndrome, whereas both of these infants died in the neonatal period. Kniest dysplasia appears to be inherited as an autosomal dominant trait; the likely transmission in this family was autosomal recessive. Roentgenograms revealed dumbbell-shaped long bones superficially similar to Kniest dysplasia, but with markedly shortened diaphyses and metaphyseal irregularities. Chondro-osseous morphology demonstrated a superficially similar foamy "Swiss cheese" appearance to the cartilage matrix, as seen in Kniest dysplasia, but there were distinctly different changes in the growth plate and resting cartilage. Ultrastructurally, the chondrocytic endoplasmic reticulum was found to have an appearance different from that observed in either normal or Kniest cartilage. These cases likely represent a distinct chondrodysplasia.

A fetus at risk for asphyxiating thoracic dysplasia was studied with ultrasound examination at 16, 18, and 23 weeks of pregnancy. Definite shortness of fetal femora was observed. Radiographic and histologic examinations after pregnancy termination confirmed the diagnosis. Asphyxiating thoracic dysplasia appears to be one of an increasing number of skeletal dysplasias that can be diagnosed prenatally with ultrasound.

Fibrochondrogenesis is a distinct, neonatally lethal, short-limb skeletal dysplasia which was first described in a single patient in 1978. We report the radiographic and morphologic studies of 2 additional unrelated stillborn infants with fibrochondrogenesis. This syndrome has distinct radiographic and chondro-osseous morphologic defects different from those seen in the other known skeletal dysplasias. The long bones are short and dumbbell-shaped with metaphyseal flare. The spine is platyspondylic with superior-inferior clefting defects, and the ribs are short and distally cupped. The growth-plate cartilage is grossly disorganized and has a densely fibrous collagenous matrix when examined by light and electron microscopy. Light, transmission, and scanning electron microscopy shows diaphyseal and metaphyseal trabecular bone to be normal.

In 46 preterm infants with RDS the patency of the ductus arteriosus was established by single film aortography or by clinical diagnosis and confirmation at surgery. The estimated left-to-right shunt through the PDA by aortogram correlated well with the heart size and the clinical diagnosis of heart failure. In 14 infants massive cardiomegaly and heart failure with a PDA occurred before the appearance of a heart murmur. Twelve infants had severe RDS and 34 had mild or moderate RDS. Massive cardiomegaly occurred significantly earlier in infants with severe RDS. It is suggested that ductal ligation is indicated when an infant with massive cardiomegaly requires IPPV and whose aortagram shows that all of the contrast material is in the pulmonary arteries and none in the aortic arch. A heart murmur may or may not be present.

We report on five cases of lethal Pena-Shokeir syndrome from three families with affected sibs. In addition to multiple anklyoses, camptodactyly, facial anomalies, and pulmonary hypoplasia, one fetus had pterygia of the neck and axillae and cardiac hypoplasia. Radiographic changes are nonspecific and probably are related to a lack of intrauterine movement. Our data and review of the literature suggest that pterygium formation is one of the manifestations of the Pena-Shokeir syndrome. A recently described lethal form of the recessively inherited multiple pterygium syndrome may represent a severe form of the Pena-Shokeir syndrome.

We describe the clinical, radiographic, histopathologic, and ultrastructural features of a distinct neonatal lethal chondrodysplasia inherited as an autosomal recessive trait. The characteristic radiographic findings consist of flattened, hypoplastic vertebral bodies; short ribs; hypoplastic iliac bones with "a snail-like" configuration; short, broad long-bones with dumbbell-like appearance; short and wide fibula; and precocious ossification of the tarsus. Chondro-osseous histology is characteristic with hypervascularity, increased cellular density, and normal size chondrocytes with a centrally located round nucleus and absence of lacunar space. Because of the snail-like radiographic appearance of the pelvis in this disorder, we propose the name "Schneckenbecken dysplasia" (ie, German for snail pelvis).

Diastrophic dysplasia is a distinct autosomal recessive disorder originally described in 1960. Since that time, a number of patients with similar but less severe involvement have been diagnosed as having a "diastrophic variant" disorder. This study reviews the radiological features of classic diastrophic dysplasia and compares them with the radiological findings in 26 patients with the diastrophic variant disorder. It is concluded that there is a wide variability in the phenotypic expression of diastrophic dysplasia even within sibships, and that cases of diastrophic variant disorder are actually mild forms of diastrophic dysplasia.

Two sibs, the offspring of consanguineous parents, presented with severe short-limb dwarfism and distinct chondro-osseous, radiologic, and histologic appearance. The first sib presented at 30 wk with severe hydrops following fetal death; the second was detected by ultrasonography at 20 wk. Radiologic abnormalities included an unusual “moth-eaten” appearance of the markedly short long bones, bizzare ectopic ossification centers, and marked platyspondyly with unusual ossification centers. Marked extra-medullary erythropoiesis was present in both fetuses, and chondro-osseous histology was characterized by marked disorganization of tissue with interspersed masses of cartilage, bone, and mesenchymal tissue. These sibs appear to have a distinct previously unreported autosomal recessive skeletal dysplasia, which can present as hydrops fetalis.

To determine the relationship between so-called "diastrophic variant" and diastrophic dysplasia, four patients considered to have the variant condition were studied in detail and compared to 67 patients (including 17 sets of affected sibs) considered to have classical diastrophic dysplasia. Analysis of the combined clinical, radiographic, histologic, and genetic data indicates that there is wide variability in the phenotypic expression of diastrophic dysplasia, even within sibships, and that those individuals previously labeled as having "diastrophic variant" appear to have mild diastrophic dysplasia.

Our experience with 12 patients with metatropic dysplasia has demonstrated two important and treatable complications: odontoid hypoplasia with subluxation of the first and second cervical vertebrae, and ventriculomegaly. Hypoplasia and lack of ossification of the odontoid process were noted in all cases. Subluxation of these two vertebrae was demonstrated in all six patients who had lateral flexion-extension radiographs; three had subluxation even in a neutral position, and sudden odontoid dislocation developed in another after a simple fall. Four individuals have had surgical fusion of the cervical vertebrae; one child died suddenly, 1 week before scheduled surgery. In the three patients in whom computed tomography scans of the head were obtained, enlarged ventricles were found; one had symptomatic increased intracranial pressure and required a shunt. We recommend that odontoid hypoplasia be evaluated in all patients with metatropic dysplasia. If subluxation is proved, atlantoaxial fusion should be performed before damage to the cervical part of the spinal cord results. Serial head circumference measurements and evaluation for hydrocephalus are also recommended.

The Kniest syndrome is a newly defined chondrodystrophy consisting of disproportionate dwarfism with kyphoscoliosis, flat facies with prominent eyes, myopia, cleft palate, hearing loss and limited joint motion. As a result of a collaborative study of 12 patients, the roentgenographic features of this syndrome have been found to be diagnostic.The major roentgenographic features consist of:1. Flat, markedly elongated irregular vertebral bodies, which have superior-inferior defects in their midportion during infancy and early childhood.2. Dumbbell shaped long bones which in later life show epiphyseal ossification delay and irregularity, as well as expanded metaphyses with a cloud-like effect on both sides of the epiphyseal plate.3. Characteristic flattened and squared off epiphyses of the hands with joint space narrowing.Biopsies of costochondral junction and iliac crest reveal identical histologic and ultrastructural abnormalities which differ from all other chondrodystrophies. Throughout the cartilage are ...

Analysis of 9 cases of bilateral bent limbs (campomelia) and dwarfism, as well as a review of the literature, indicate that campomelic syndrome appears to be a well-defined distinct disorder which the authors call long-limbed campomelic syndrome. Other neonates with congenital bent-limbed dwarfism can be classified as having short-limbed campomelic syndrome, and among these at least two distinct forms have been delineated--the craniosynostotic and the normocephalic form. Congenital bent bones also occur in a variety of generalized disorders of ossification that must be distinguished from these well-defined types of campomelic dwarfism.

Seven commonly used arthrographic contrast media were examined in vitro for bactericidal effects against Staphylococcus aureus under various conditions simulating clinical settings, using a wide range of bacterial populations (10(1) to 10(8) colony-forming units per ml). The media tested were: sodium diatrizoate and megulumine diatrizoate (E.R. Squibb and Sons, Renogragin-60 and Renografin-76), megulumine diatrizoate (E. R. Squibb and Sons, Renografin-M-60), sodium iothalamate and megulumine iothalamate (Mallinckrodt Chemical Works, Vascoray), sodium iothalamate (Mallinckrodt Chemical Works, Conray 400), meglumine iothalamate (Mallinckrodt Chemical Works, Conray 60), and sodium diatrizoate (Winthrop Laboratories, Hypaque sodium 50%). Effects secondary to the contrast medium used, dilution ratios of the specimens, and time elapsed between the collection and cultivation of the specimens were examined. The contrast material used was found to affect bacterial growth: the Renografin materials showed a bactericidal or bacteriostatic effect, while Vascoray, the Conray materials, and Hypaque sodium 50% failed to inhibit bacterial growth. Bacterial inoculum size exhibited a direct bearing on the bactericidal or bacteriostatic effects of the Renografin but had no effect with the other media. The results indicate that Vascoray, Conray and Hypaque sodium 50% are superior to the Renografin materials for use in arthrography and other procedures in which the aspirate is submitted for microbial culture, because they interfere less with the recovery of these microorganisms.

Ultrasonographic and radiographic evaluation of a fetus at risk for osteogenesis imperfecta (O.I) type III was performed. Real-time ultrasound measurements at 15 weeks gestation were interpreted as normal, but at 20 and 22 weeks of gestation revealed marked shortening of the long bones and deformity of the femurs. The findings were confirmed by fetal radiography at 22 weeks gestation. Radiographic and histologic changes characteristic of O.I. were observed in the aborted fetus. Thus the antenatal manifestations of O.I. type III maybe severe enough to make prenatal diagnosis possible in the second trimester for families at risk for recurrence of this disorder.

The Winchester syndrome, a recently recognized inherited disorder of connective tissue, consists of dwarfism, contractures, skin lesions, corneal opacities, osteoporosis, carpal-tarsal osteolysis, and rheumatoid-like small joint destruction. We have studied the third, fourth, and fifth recognized cases of this disorder and find: (1) progressive lysis of carpal and tarsal bones; (2) replacement of bone and cartilage by dense fibrous tissue containing abnormal blood vessels; (3) scanty trabecular and cortical bone, but normal resting cartilage and growth plates; (4) hypervascularity apparently associated with osteolysis at large joints; and (5) widespread proliferation of ultrastrurally abnormal fibroblasts. Although this disorder was originally postulated to be a new mucopolysaccharidosis, we find no evidence for a lysosomal storage disease, and propose reclassification of this disorder as a nonlysosomal connective tissue disease.

Three cases of congenital lipomatosis involving the thoracic region posteriorly are presented delineating the natural history of the disease and depicting underlying bone and soft tissue changes. The rib widening and pleural thickening appear to be related to increased intercostal vascularity feeding the overlying tumor, as delineated by angiography. This entity is not described in the radiologic literature.

A 6-month-old female with a lifelong history of respiratory distress became increasingly difficult to manage and required right upper and middle pulmonary lobectomies for worsening emphysema and mediastinal shift. The postoperative course was stormy and confusing and the patient died despite emergency tracheostomy. The autopsy disclosed an anomalous bronchus to the right lower lobe, originating from the left mainstem bronchus. In addition, the left main pulmonary artery was positioned posterior to the left mainstem bronchus. Two other cases of bridging bronchus have been reported, but the association with posterior left pulmonary artery has not been described.

Three children demonstrating gastric rugal enlargement as their primary disease are reported. Two had the histologic features of Menetrier’s disease and in 1 of these patients cytomegalic inclusion bodies were found in the gastric wall. The third patient had histology consistent with angioneurotic edema.Some other diseases showing similar roentgenologic appearances are demonstrated and discussed.

Hip arthrography was performed on a group of nine patients whose diagnoses included various types of multiple epiphyseal dysplasia and spondyloepiphyseal dysplasia. The cartilage anlage of the capital femoral epiphysis was normal in size and contour in all but one patient, suggesting faulty, incomplete, or delayed ossification of the epiphysis in both multiple epiphyseal dysplasia and spondyloepiphyseal dysplasia. The multiple epiphyseal dysplasia patients, as well as those with a dominant form of spondyloepiphyseal dysplasia, had decreased joint space volumes probably related to the degenerative arthritis which commonly develops in such cases. It is not possible to distinguish between multiple epiphyseal dysplasia and spondyloepiphyseal dysplasia at arthrography.

Radiographic review was obtained of 30 patients with Niemann-Pick disease. The radiologic features are hepatosplenomegaly, pulmonary infiltrations, osteoporosis with coxa valga, long-bone expansion with modeling defects, and metacarpal widening. Some definite group specificity is appreciated but changes appear related to longevity as well as to expression of the disease. Previously undescribed features are bone changes similar to those of Gaucher's disease, diffuse lung and liver calcifications, and a notch defect of the proximal humerus. The bone and lung changes are described in detail and differentiated from similar findings in other disease entities.

Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are autosomal dominant osteochondrodysplasias that result in mild to severe short-limb dwarfism and early-onset osteoarthrosis. PSACH and some forms of MED result from mutations in the gene for cartilage oligomeric matrix protein (COMP; OMIM 600310 [http://www3.ncbi.nlm. nih.gov:80/htbin-post/Omim/dispmim?600310]). We report the identification of COMP mutations in an additional 14 families with PSACH or MED phenotypes. Mutations predicted to result in single-amino acid deletions or substitutions, all in the region of the COMP gene encoding the calmodulin-like repeat elements, were identified in patients with moderate to severe PSACH. We also identified within this domain a missense mutation that produced MED Fairbank. In two families, one with mild PSACH and the second with a form of MED, we identified different substitutions for a residue in the carboxyl-terminal globular region of COMP. Both the clinical presentations of these two families and the identification of COMP-gene mutations provide evidence of phenotypic overlap between PSACH and MED. These data also reveal a role for the carboxyl-terminal domain in the structure and/or function of COMP.

The case report is presented of a neonate with a unilateral multicystic dysplastic kidney. An intravenous pyelogram revealed septations throughout this kidney with late pooling of contrast media within the cystic structures. The pathological data stresses the presence of normal appearing glomeruli interspersed between the dysplastic cystic parenchyma. The possible etiologies for the septation sign and puddling phenomenon are discussed.

Two siblings, one male and one female, were noted to have a distinct skeletal dysplasia. The clinical and radiographic features resemble those observed in Kniest dysplasia and Rolland-Desbuquois syndrome, but important differences were noted. Specifically, these two patients have microstomia, "pursed" lips, and ectopia lentis, and their radiographs reveal no coronal clefts. Chondro-osseous features also differ from those observed in either of the other disorders. Scattered dense patches consisting of collagen fibers 10 to 30 times broader than normal are seen scattered throughout the cartilage matrix; the "Swiss cheese" appearance characteristic of Kniest dysplasia is not observed. These patients appear to have a new skeletal dysplasia, most likely inherited in an autosomal recessive fashion.

We report two sporadic cases with a previously undescribed skeletal dysplasia lethal in the neonatal period. The syndrome is characterised clinically by striking rhizomelic shortness of the limbs and radiographically by absence or hypoplasia of the humeri, hypoplastic vertebrae, absent fibulae and ossification in only the distal phalanges of the hands. Morphologic studies show hypocellular areas of growth plate cartilage containing occasional multinucleated giant cells.

This paper describes a newborn with a number of clinical manifestations compatible with duplication 16p due to a 46, XY, -7, +der (7), t(7;16) (p22;p13) pat karyotype. In addition, the baby had chondrodysplasia punctata, whose distribution of lesions did not match any of the well-documented forms of these disorders. The baby also had microcornea and lacked a gallbladder, two features, in addition to chondrodysplasia punctata, that have not previously been noted in cases of duplication 16p.

The occurrence of Hirschsprung's disease, with histologically verified colonic aganglionosis, in only 1 of 2 prematurely born and presumed identical (monozygotic) twins is reported. The occurrence of monozygotic twinning was supported by the observed sharing of a single and common placenta and by ABO and HLA identity of peripheral blood erythrocytes and leukocytes. The affected twin was of a slightly lower birth weight and experienced early respiratory distress, necrotizing enterocolotis, and more prolonged umbilical artery catheterization (not encountered in the unaffected twin). This, to the authors' knowledge, is the first reported occurrence of Hirschsprung's disease discordant in monozygotic twins. The literature relating to genetic and environmental factors in clinical and experimental colonic aganglionosis is reviewed and speculation is presented regarding the occurrence of colonic aganglionosis discordant in monozygotic twins as reported here.

We report a previously undescribed association of severe short-limbed dwarfism and macular colobomas with histological changes of cartilage resembling to some extent those of diastrophic dysplasia. Chance occurrence of two rare disorders due to different causes is considered unlikely and the patient is presumed to have a syndrome of, as yet, unknown cause.