Atelosteogenesis type III: long term survival, prenatal diagnosis, and evidence for dominant transmission.

We describe two additional instances of atelosteogenesis, type III, in a woman and her son. Clinical and radiographic information concerning these individuals allows further definition of this rare skeletal dysplasia. This is the first documentation of survival to adulthood of an individual with this disorder, of prenatal diagnostic assessment of an affected individual, and of vertical transmission suggestive of autosomal dominant inheritance. The clinical and radiologic phenotype of atelosteogenesis, type III overlaps with that of another skeletal dysplasia, autosomal dominant Larsen syndrome; these most likely represent allelic conditions.

Previously undescribed syndrome of spondylometaphyseal dysplasia, osteocartilaginous metaplasia of long bones, and progressive osteolysis of distal phalanges.

We present the findings and clinical course of a Caucasian woman (now age 23 1/2) who has been treated since early childhood for a previously undescribed syndrome of painful osteocartilaginous metaplasia of long bone metaphyses and painful distal phalangeal osteolysis and soft tissue swelling. Despite extensive evaluations and attempts at effective treatment, the cause and pathogenesis of her unique musculoskeletal disorder remain elusive.

Progressive laryngotracheal stenosis with short stature and arthropathy.

Laryngotracheal stenosis is rare in adults, especially in the absence of a malignancy. It is most commonly caused by fibrosis following endotracheal intubation or tracheal trauma. Other conditions causing progressive airway narrowing include the mucopolysaccharidoses and autoimmune disorders. With the exception of storage diseases, there are no well-defined genetic disorders with progressive airway narrowing as a common complication. We have evaluated three unrelated individuals with this potentially life-threatening finding, all of whom have a previously unrecognized condition. Each patient had short stature and joint stiffness with no evidence for infectious, inflammatory, or metabolic diseases as a cause of their condition. None of our patients had clinical findings indicative of known skeletal dysplasias or storage diseases. They had minor facial anomalies which included deeply set eyes, bushy eyebrows, and flat midface. Given the unique findings of our patients including adult onset critical tracheal stenosis, short stature, progressive joint limitation, and distinct facial anomalies, we conclude that they have a previously undescribed condition.

Sponastrime dysplasia: diagnostic criteria based on five new and six previously published cases.

Sponastrime dysplasia is a dwarfing autosomal recessive bone dysplasia, the diagnosis of which is based on a combination of clinical and radiological features. The radiological features are more specific than the clinical ones. We have developed diagnostic radiological criteria based on information from our five cases and from six previously published ones.

Sponastrime dysplasia: five new cases and review of nine previously published cases.

Sponastrime dysplasia (SD) is a dwarfing autosomal recessive short-limb bone dysplasia. The diagnosis is established by a combination of clinical and radiological findings of which the radiological are the more specific. The current diagnostic criteria are ambiguous as demonstrated by the fact that, in our opinion, three of the five patients reported since the original article do not have this condition. Comparison of our five patients and the 9 published patients has led to development of more specific diagnostic criteria. Previously undescribed complications of this condition are subglottic stenosis and tracheo-broncho-malacia, developmental coxa vara, and avascular necrosis of the capital femoral epiphyses.

Kniest dysplasia: radiologic, histopathological, and scanning electronmicroscopic findings.

We describe severe neonatal Kniest dysplasia. Radiological findings in a severe case include short bowed tubular bones with exaggerated metaphyseal flare, moderate platyspondyly with vertical clefts of the vertebral bodies, and characteristically shaped iliac bones. Pathologic findings included a disorganized physeal growth plate, soft crumbly cartilage with a "Swiss-cheese" appearance, and diastase resistant intracytoplasmic inclusions in the resting chondrocytes. Transmission electronmicroscopy showed dilated cisternae of rough endoplasmic reticulum with finely granular material of accumulated protein. Scanning electronmicroscopy documented striking fragmentation and disintegration of collagen fibrils resulting in a web-like pattern and large open cyst-like spaces, and deficiency and disorganization of the collagen fibrils.

Genetic heterogeneity in multiple epiphyseal dysplasia.

Multiple epiphyseal dysplasia (MED) comprises a group of hereditary chondrodysplasias in which there are major anatomic abnormalities of the long tubular bones. The Fairbank and Ribbing types are the most frequently cited types of MED. They are primarily defined radiographically and are autosomal dominant conditions. Recently, MED in one family was shown to map to the pericentromeric region of chromosome 19 and is probably allelic to pseudoachondroplasia. We have tested linkage with six short tandem repeat markers from chromosome 19 to autosomal dominant MED in one four-generation family and to MED in a unique family with three of seven siblings affected and with unaffected parents. Autosomal dominant MED in family 1 was linked with a maximum LOD score, at D19S212, of 3.22 at a recombination fraction (theta) of .00. Linkage to chromosome 19 was excluded with MED in the other family, under both autosomal recessive and autosomal dominant, with either reduced-penetrance or germ line-mosaicism models. Linkage to candidate genes COL9A1, COL9A2, and COL11A2 was tested and excluded for both genetic models in this family. COL11A1 was excluded under a recessive model. We have confirmed linkage of autosomal dominant Fairbank MED to chromosome 19 and have demonstrated that MED is genetically heterogeneous.

Spondylocarpotarsal synostosis syndrome (with or without unilateral unsegmented bar).

Spondylocarpotarsal synostosis syndrome is characterized by autosomal recessive inheritance, failure of normal spinal segmentation causing symmetrical block vertebrae or scoliosis, and lordosis. There is a disproportionately short trunk. Some patients have a unilateral unsegmented bar. Other skeletal changes include carpal synostosis, usually capitate-hamate and lunate-triquetrum. Tarsal synostoses were present in patients in whom the feet were radiographed. Stature is short. The feet are flat. Cleft palate and sensorineural or mixed hearing loss are variable manifestations. We have reviewed the literature and present 6 new patients, 2 of them sibs.

Patient with double heterozygosity for achondroplasia and pseudoachondroplasia, with comments on these conditions and the relationship between pseudoachondroplasia and multiple epiphyseal dysplasia, Fairbank type.

We present a 7 1/2-year-old girl with achondroplasia and pseudoachondroplasia. Her mother has achondroplasia and her father has pseudoachondroplasia. Radiographic manifestations of these two conditions from infancy to age 6 years are outlined. The findings in this patient are compared with those of achondroplastic patients and pseudoachondroplastic patients of similar ages. Our review of radiographs of many pseudoachondroplastic patients and subsequently of those of patients with multiple epiphyseal dysplasia (MED), Fairbank type, reinforced our opinion that pseudoachondroplasia and multiple epiphyseal dysplasia, Fairbank type, are closely related conditions. MED, Fairbank type, may be the mildest form of pseudoachondroplasia. Recently published electron microscopic findings also suggest this.

Further delineation of spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type, with emphasis on diagnostic features.

Further delineation of a generalized bone dysplasia which we call spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type is presented. This dwarfing condition has several serious complications, with the most common cause of death being spinal cord damage secondary to atlantoaxial instability. It is a heritable condition with an autosomal recessive mode of transmission. Radiologic diagnostic criteria are developed on the basis of studies in 8 patients with the oldest being between 4 and 5 years old. The condition is clinically and radiographically apparent neonatally or in early infancy, and it is probable that all or almost all affected individuals will come to medical attention in the age range screened by this study.

Spondylo-meta-epiphyseal dysplasia (SMED), short limb-hand type: a congenital familial skeletal dysplasia with distinctive features and histopathology.

We report on a "new" severe short-limb bone dysplasia which can be labeled descriptively a spondylo-meta-epiphyseal dysplasia. The 3 patients were born to 2 unrelated Sepharadic Jewish families and a Puerto Rican family. Clinical abnormalities include small stature with short limbs including short hands, a short nose with wide nasal bridge and wide nostrils, a long philtrum, ocular hypertelorism, retro/micrognathia, and a narrow chest. Radiological abnormalities include platyspondyly, short tubular bones with very abnormal metaphyses and epiphyses beyond early infancy, short ribs, and a typical evolution of bony changes over time. Chondroosseous morphology and ultrastructure document sparse matrix and degenerating chondrocytes surrounded by dense amorphous material in the 1 patient studied. Consanguinity is present in 1 family. In addition to the described patient, 2 other short-limb sibs, who did not survive infancy, were born into this family. Even in the absence of any photographic or radiologic documentation of these other 2 infants, autosomal recessive mode of inheritance seems probable.

Dominant mesomelic dysplasia, ankle, carpal, and tarsal synostosis type: a new autosomal dominant bone disorder.

A new type of mesomelic dysplasia was in 3 generations of a large Thai family. It is characterized by bilateral symmetrical marked shortening of the ulnae and shortening and bowing of the radii. The proximal fibula is usually short and synostoses are present between the tibia and fibula and the small malformed calcaneus and talus. The prominent calcanei on the ventral surfaces of the distal fibulae are a characteristic feature of the new type. Carpal and tarsal synostoses are present in some affected people. All affected individuals walk on the tips of their toes with the dorsal foot deviated laterally. The deformities of the radius and ulna somewhat resemble those of mesomelic dysplasia, Langer type, but otherwise the condition is distinctly different. This new mesomelic dysplasia is an autosomal dominant trait with complete penetrance and variable expressivity over 3 generations.

Short rib syndrome Beemer-Langer type with polydactyly: a multiple congenital anomalies syndrome.

A male fetus with short rib (polydactyly) syndrome, Beemer-Langer type was aborted at 30 weeks' gestation because of abnormalities visualized on sonography. This is the first documented case with polydactyly in this recently defined entity. The clinical, radiological, and pathological findings, especially of the bones, are described. The differential diagnosis of this entity is discussed.

Radiographic features of craniometadiaphyseal dysplasia, wormian bone type.

We describe the radiographic findings in two siblings with a previously unrecognized craniotubular bone dysplasia. We call this condition craniometadiaphyseal dysplasia, wormian bone type. Because the parents of the siblings are consanguineous, this is probably a genetically determined condition with an autosomal recessive type of transmission. The findings in the siblings are compared with those of a woman with the same condition, previously reported as an example of craniometaphyseal dysplasia. The combination of findings in these patients seems diagnostic: characteristic skull changes including multiple wormian bones; wide long tubular bones without normal metaphyseal flaring; wide short tubular bones without normal diaphyseal constriction and sometimes actual diaphyseal expansion; and wide ribs and clavicles.

Spondylometaphyseal dysplasia, corner fracture type: a heritable condition associated with coxa vara.

The authors present the radiographic features of a previously incompletely delineated bone dysplasia, which they call spondylometaphyseal dysplasia, corner fracture type. This is a dominant heritable condition associated with short stature and developmental coxa vara. The progressive hip deformity usually causes significant disability requiring surgical correction. Developmental coxa vara, simulated corner fractures of long tubular bones, and vertebral body abnormalities result in a diagnostic constellation. Knowledge of these distinctive radiologic features allows accurate diagnosis, which in turn should lead to appropriate genetic counseling and possibly to earlier, more efficacious surgical treatment of the coxa vara.

A severe autosomal recessive acromesomelic dysplasia, the Hunter-Thompson type, and comparison with the Grebe type.

Two siblings with a short-limb dwarfing condition which we call acromesomelic dysplasia, Hunter-Thompson type are reported. Abnormalities are limited to the limbs and limb joints in this severe form of dwarfism. The middle and distal segments of the limbs are most affected. The lower limbs are more affected than the upper. We are aware of one previously published case of this entity reported by A. G. W. Hunter and M. W. Thompson in 1976. Dislocations of the elbows and ankles were present in all three patients and dislocations of the hips and knees in two. One of the siblings who did not have hip and knee dislocations clinically resembled Grebe chondrodysplasia, another severe acromesomelic dwarfing condition. However, radiological analysis suggests that while acromesomelic dysplasia, Hunter-Thompson type and Grebe chondrodysplasia are related, they are not identical. Grebe chondrodysplasia has been established as an autosomal recessive trait. It appears probable that the entity we describe has the same mode of genetic transmission.

Thanatophoric dysplasia and cloverleaf skull.

Nine infants with thanatophoric dysplasia (TD) and cloverleaf skull (CS) are reported. Twenty-two previously published CSTD cases are reviewed. These CSTD cases are compared to cases of TD without CS. It is concluded that there are two types of TD: type 1, with curved femora and very flat vertebral bodies; and type 2, with straight femora and taller vertebral bodies. Consistent but subtle histopathological characteristics differentiate the two types. Only a very few type 1 cases have CS, and the CS is mild. Almost all type 2 cases have severe CS.

Three conditions in neonatal asphyxiating thoracic dysplasia (Jeune) and short rib-polydactyly syndrome spectrum: a clinicopathologic study.

Clinicopathologic examination of eight patients with asphyxiating thoracic dysplasia (Jeune; ATD) disclosed two different types, which were designated as type 1 and type 2. Type 1 ATD was characterized by the presence of radiologically irregular metaphyseal ends and histopathologically irregular cartilage bone junction with patchy distribution of physeal zone of hypertrophy. Type 2 ATD showed radiologically smooth metaphyseal ends and histopathologically diffusely retarded and disorganized physes with smooth cartilage bone junctions. Examination of four patients with the "Verma-Naumoff" short rib-polydactyly syndrome showed many radiologic and pathologic features similar to those of type 1 ATD. Differential diagnosis of these three osteochondrodysplasias is discussed along with chondroectodermal dysplasia (Ellis-van Creveld), short rib-polydactyly syndrome type 1 (Saldino-Noonan), short rib-polydactyly syndrome type 2 (Majewski), and the new short rib syndrome reported by Beemer et al [1983].

A new skeletal dysplasia: clinical, radiologic, and pathologic findings.

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.