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Geleophysic dysplasia is characterized by typical facies ("happy natured"), small hands and feet, short stature, hepatomegaly, and progressive cardiac disease. We describe five patients (two of whom are siblings) with this disorder and document its variable expressivity. The facies were strikingly similar with small nose, anteverted nostrils, broad nasal bridge, and long thin upper lip with flat and long philtrum. Behavior, development, and intelligence were normal. Growth delay was noticed during infancy, and the two patients who completed normal puberty had marked short stature (140 and 150 cm), with relatively lean body habitus. The hands and feet were small, with short, plump tubular bones and broad proximal phalanges, associated with marked limitation in motion of fingers and wrists. The liver was enlarged after the age of 3 years. Two patients had mild mitral and tricuspid valve stenosis and one had severe aortic stenosis. The most severely affected child died at 3 1/2 years of age of airway obstruction as a result of progressive tracheal narrowing. Lysosomal storage vacuoles were found in skin epithelial cells from three patients whose skin was examined, and in the tracheal mucosa, liver, cartilage and macrophages of the child who died. The basic defect of this autosomal recessive lysosomal storage disease remains to be determined.

tive study of unexplained nausea and vomiting after marrow transplantation. Transplantation 1986;42:602-7. 4. Spencer GD, Shulman HM, Myerson D, Thomas ED, McDonald GB. Diffuse intestinal ulceration after marrow transplantation: A clinicopathologic study of 13 patients. Hum Pathol 1986;17:621-33. 5. Pass RF, Whitley R J, Diethelm AG, Whelchel JD, Reynolds DW, Alford CA. Cytomegalovirus infection in patients with renal transplants: Potentiation by antithymocyte globulin and an incompatible graft. J Infect Dis 1980;142:9-17. 6. Converse P, Hess A, Tutschka P, Santos GW. Effect of cyclosporine on the response of normal human lymphocytes to cytomegalovirus in vitro. Infect Immun 1983;41:1226-33. 7. Chachoua A, Dieterich D, Krasinski K, et al. 9-(1,3-dihydroxy-2-propoxymethyl) guanine (gancyclovir) in the treatment of cytomegalovirus gastrointestinal disease with the acquired immunodeficiency syndrome. Ann Intern Med 1987;107:1337. 8. Weber JN, Thorn S, Barrison I, et al. Cytomegalovirus colitis and oesophageal ulceration in the context of AIDS: Clinical manifestations and preliminary report of treatment with Foscarnet (phosphonoformate). Gut 1987;28:482-7. 9. Rakela J, Wiesner RH, Taswell HF, et al. Incidence of cytomegalovirus infection and its relationship to donor-recipient serologic status in liver transplantation. Transplant Proc 1987; 19:2399-2402. 10. Snydman DR, Werner BG, Heinze-Lacey B, et al. Use of cytomegalovirus immune globulin to prevent cytomegalovirus disease in renal-transplant recipients. N Engl J Med 1987;317-1049-54.

Cerebral gigantism is a syndrome consisting of characteristic dysmorphic features, accelerated growth in early childhood, and variable degrees of mental retardation. Its etiology and pathogenesis have not been defined. Three families are presented with multiple affected members. The vertical transmission of the trait and equal expression in both sexes in these families indicates a genetic etiology with a dominant pattern of inheritance, probably autosomal. As in previously reported cases, extensive endocrine evaluation failed to define the pathogenesis of the accelerated growth present in this disorder.

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.

Standard growth curves for achondroplasia, the most common form of short-limbed dwarfism, have been constructed based on measurements of height, growth velocity, upper and lower segment, and head circumference in 400 achondroplastic dwarfs. These standard curves provide the basis to assess normal growth in these individuals, to aid in the determination of superimposed disorders, and to assess any growth accelerating therapy.

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 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.

Phenotypic analysis of the reported cases of partial G monosomy indicates that deletions of a G chromosome can result in at least two distinct syndromes. The clinical features characterizing each of these entities are discussed; a child with the second syndrome is described in detail.

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.

A great deal of controversy has existed concerning the effects of maternal varicella infection on the fetus. The purpose of this study was to establish a firm association between congenital anomalies of infants and maternal varicella infection (VI) in pregnancy. To date, prospective studies have failed to establish this association due to the rarity of index cases. The infant population in the present study is derived from a retrospective analysis of cases reported in the English language literature, as well as a personal case. The criteria used for the fetal Varicella Syndrome (FVS) were: 1. evidence of maternal VI during pregnancy, 2. presence of congenital skin dermatome lesions characteristic of VI and 3. immunologic proof of in-utero VI of the infants. Eighteen children who fulfilled the above criteria constituted the patient population identified as having fetal varicella syndrome (FVS). These children had a characteristic spectrum of anomalies which included: maternal VI at ≤ 20 weeks' gestation (8-20), all had skin lesions corresponding to dermatomes, 81% were female, 50% small for dates, 47% preterms, 89% had neurologic anomalies, 78% had eye anomalies, 72% had skeletal hypoplasia, 28% had gastrointestinal anomalies and 28% had urologic anomalies. Thus, it is apparent that maternal and subsequent fetal varicella infection during early pregnancy can result in a characteristic spectrum of anomalies which can be referred to as the “fetal varicella syndrome.”

peroxidase activity in the leukocytes of patients with the autosomal recessive form of CGD. The present results suggest that not all cases of autosomal recessive CGD can be ascribed to a deficiency of leukocytic glutathione peroxidase. Indeed, it is possible that the enzyme deficiency previously described in two female patients 6 was a reflection of a multiple enzyme deficiency and the lack of glutathione peroxidase had no causal relationship to the disease itself. Alternatively, it seems quite possible that the syndrome commonly referred to as CGD is not a single entity but may be encountered in the face of a deficiency of one of a number of critical enzyme activities.

Thirteen infants with achondroplasia and sudden unexpected death or unexplained apnea were discovered through nonsystematic retrospective case collection. Most were initially thought to have died from sudden infant death syndrome. However, historical and pathologic findings suggest that many of these infants had apnea and sudden unexpected death secondary to acute or chronic compression of the lower brainstem or cervical spinal cord. Infants with achondroplasia evidently are at considerably increased risk for such deaths between 1 month and 1 year of age. Appropriate intervention, given these previously unrecognized risks, may include cervical restraint, polysomnographic evaluation, and apnea monitoring.

Pseudodiastrophic dysplasia is a distinct disorder that differs from diastrophic dysplasia on the basis of clinical, radiographic, and chondro-osseous histopathologic findings. In addition to the rhizomelic shortening of the limbs and severe clubfoot deformity, which suggest the diagnosis of diastrophic dysplasia, distinguishing features are elbow and proximal interphalangeal joint dislocations, platyspondyly, and scoliosis, which are observed in infancy. This disorder has been reported previously in three infants, all of whom died in the first year of life. Two of these were sisters, suggesting autosomal recessive inheritance. We report four new patients with this distinct skeletal dysplasia, including two children now older than 4 years of age. In both of these patients neonatal contractures have improved with physical therapy and scoliosis has progressed significantly.

Twelve infants, initially considered to have thanatophoric dysplasia, were studied by a combined radiographic-histochemical-biochemical approach. Three distinct forms of platyspondylic lethal neonatal short-limbed dwarfism could be distinguished: (1) Thanatophoric type, (2) Torrance type, and (3) San Diego type. The latter two disorders had similar radiographic abnormalities that were clearly different from those of typical thanatophoric dysplasia. All three disorders had clearly different chondroosseous histopathologic abnormalities. Preliminary biochemical studies have revealed different electrophorectic abnormalities in solubilized type II collagen chains of cartilage in each of these three disorders.

The Grebe syndrome is a nonlethal form of severe short-limbed dwarfism which was previously called “achondrogenesis-Brazilian or Grebe type.” We have studied three patients with severe short-limbed dwarfism originally considered to have this syndrome. On re-evaluation of their clinical and radiographic features, only one of them had the typical features of the Grebe chondrodysplasia, whereas the other two appear to have clearly distinct, previously unreported skeletal dysplasias. These patients illustrate the heterogeneity that exists among the nonlethal forms of severe short-limbed dwarfism.

SXATUR~, the quantitative measure of height, varies widely within each ethnic group with a fairly normal distribution. Of the numerous patients whom the physi, clan encounters because of short stature, relatively few are pathologically small in the context of family and ethnic background. Thus it is imperative that the physician be able to differentiate pathologic short stature from the lower end of the normal curve before embarking on a complex diagnostic evaluation. We shall provide a pathophysiologic background for the evaluation of short stature by outlining the normal human growth curve, the physiologic mechanisms that participate in the growth process, and the manner in which these processes can be disturbed. NORMAL HUMAN GROWTH A growth curve, common to all individuals, has characteristics which are shared by many other primates I ~ (Fig. 1); it is characterized by rapid fetal growth, quick deceleration of growth following birth, a period of relatively

Three children, two of them siblings, with severe combined immunodeficiency and adenosine deaminase deficiency died within the first six months of life from the complications of acute bacterial infections. Subtle radiographic abnormalities were seen at the costochondral junctions, at the apophysis of the iliac bones, and in the vertebral bodies. At autopsy, the thymus showed evidence of early differentiation and, in one instance, aborted Hassall's corpuscles. Histologic study of the bone disclosed lack of organized cartilage columnar formation, large lacuni containing hypertrophied cells, and lack of trabecular formation with uninterrupted areas of calcified cartilage. These changes are distinctly different from those observed in the metaphyseal chondrodysplasias or in other chondrodystrophies.

Achondrogenesis has traditionally been divided into type I (Parenti-Fraccaro) and type II (Langer-Saldino). We studied the clinical, radiologic, and morphologic features of 17 cases previously diagnosed as achondrogenesis type I to define whether there is even further heterogeneity. On radiographic analysis, two distinct groups of patients were defined based on the presence or absence of rib fractures and ossification of the vertebral pedicles, ischium, and fibula. Two distinct chondroosseous morphologic patterns were observed that directly correlated with the radiographic grouping. One group had round vacuolated chondrocytes with inclusion bodies; the other had collagenous rings around the chondrocytes. We conclude that achondrogenesis type I (Parenti-Fraccaro) consists of two distinct disorders: type IA, which corresponds to the cases originally published by Houston et al. and Harris et al., and type IB, which corresponds to the case originally published by Fraccaro. Analysis of Parenti's case suggests the diagnosis of achondrogenesis type II. All three types of achondrogenesis appear to be inherited as autosomal recessive traits.

The association of oral, facial, and digital malformations has become known as the oral-facial-digital (OFD) syndrome. This syndrome is currently considered to be inherited as an X-linked dominant trait, manifested only in female subjects and lethal in themale. This paper documents the presence of OFD malformations in one girl and her two male siblings. It is concluded that this symptom complex represents at least two distinct genetic entities: OFD I, inherited as an X-linked or sex-limited autosomal dominant; and OFD II (Mohr syndrome), probably inherited as an autosomal recessive.

Clinical, radiologic, and biochemical studies are presented of a patient with a previously undescribed mucopolysaccharide storage disease. Clinical features include short stuature, hepaosplenomegaly, progressive skeletal deformities of the thorax and spine, granular inclusion in leukocytes, and frequent symptomatic pulmonary infections. Corneal clouding was not present at age 30 months. Mental retardation was not present at age 2 years, but subsequent development is lagging. Radiologic changes of "dysostosis multiplex" involved the skull, spine, ribs, and long and short tubular bones. Mycopolysacchariduria was mild. Enzyme studies on white blood cells and skin fibroblasts revealed virtual absence of the lysosomal hydrolase β-D-glucuronidase. Both parents of the proband and several of his mother's siblings had reduced levels of this enzyme, suggesting an autosomal recessive inheritance. The heterozygous carriers appear clinically and radiologically normal.

A syndrome characterized by obstruction of the nasolacrimal ducts, hypoplasia or aplasia of the lacrimal puncta, cup-shaped ears, hearing loss, dental and digital malformations is described. A Mexican father and five of his eight children are affected, suggesting an autosomal dominant mode of inheritance. The name “lacrima-auriculo-dento-digital syndrome” is proposed for this disorder.