Dyssegmental dwarfism. A new case

In a 3 1/2 month old child with micromelic dwarfism, a case of dyssegmental dwarfism is reported. This affection is characterized, on one hand, by a shortening and a squat aspect of long bones with diaphyseal curve, and on the other hand, by a trouble of vertebral segmentation associated to a variability in the size of vertebral bodies. The differential diagnosis appears adequate to differentiate the dyssegmental dwarfism from other types of neonatal chondrodysplasia, in particular from Kniest syndrome and micrognathia dwarfism.     

A distinct chondrodysplasia resembling Kniest dysplasia: clinical, roentgenographic, histologic, and ultrastructural findings

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.     

Shwachman-Diamond syndrome: Clinical,radiological and sonographic findings

Six children with Shwachman-Diamond syndrome have been diagnosed and treated in our hospital since 1986. We describe the radiological and sonographic findings of this rare disease, which is characterized by metaphyseal chondrodysplasia, neutropenia and exocrine pancreatic insufficiency. It presents with varying extremity shortening, cup deformation of the ribs, metaphyseal widening and hypoplasia of the iliac bones, as well as increased echogenicity of the normal-sized pancreas. We discuss the differential diagnosis and review the literature.     

Coronal and sagittal clefts in skeletal dysplasias

Objective. To assess the role of coronal and sagittal vertebral clefts in diagnosing skeletal dysplasias. Material and Methods. A search in the database at the International Skeletal Dysplasia Registry revealed 40 different diagnoses in which coronal or sagittal clefts were present, the major groups being: atelosteogenesis, chondrodysplasia punctata, dyssegmental dysplasia, Kniest dysplasia and short rib polydactyly syndrome. We reviewed all firm cases with both AP and lateral films of the spine in these major groups (n = 143), with patients' ages ranging from 20 weeks of gestation up to 26 years of age. Results. Ninety-four percent of all clefts were found in children less than 1 year of age, mainly located in the thoracolumbar region. Fifty-six percent of the clefts were observed in boys. Coronal clefts were more common than sagittal clefts. Clefts were most frequently observed in atelosteogenesis (88 %), followed by chondrodysplasia punctata (79 %), dyssegmental dysplasia (73 %), Kniest dysplasia (63 %) and short rib polydactyly syndrome (53 %). Conclusion. Vertebral clefts are of major diagnostic value in the groups mentioned above, especially before 1 year of age. The search did not come up with new entities in which vertebral clefts are of major diagnostic value. Received/accepted: 6 May 1998     

The clinical phenotype of β and δβ thalassemias in Greece

Based on precise evaluation of hematological findings and clinical manifestations, the relationship between genotype and clinical phenotype was studied in 475 Greek patients with and thalassemias. Almost all known genotypes are included in this series, but the most frequent was homozygous ^th high A₂ (71.6%), ^th/^th silent (7.4%), ^th/^oth high F (6.3%) and ^th/^th Dutch (6.3%).In general, the phenotype was related to the genotype, though clinical heterogeneity was detected among patients with the same genotype. The severe type of thalassemia major was most commonly found in homozygous ^th patients mainly of ^o/^o and ^o/⁺ genotypes while homozygous ⁺ patients had milder clinical manifestation. Furthermore a small group of patients, characterized as homozygous ⁺⁺ (HbF<30%) had mild thalassemia intermedia. In addition mild thalassemia intermedia was principally related with homozygous ^oth, and compound heterozygous ^th/^th silent I, and less frequently with other genotypes such as compound heterozygous with ^th/^th Dutch, ^th/^th silent II, ^th/^th high F or Lepore.It was shown that precise genetic characterization and clinical evaluation is of primary importance in predicting the prognosis and formulating the proper treatment for the individual patient with thalassemia.     

Chondrodysplasia punctata — Rhizomelic form

Pathologic, ultrastructural and radiologic studies are described on 3 infants with the rhizomelic form of chondrodysplasia punctata. Radiologic criteria in the young infant include radiolucent coronal clefts dividing all or most of the thoracic and lumbar vertebral bodies, short humeri with flared metaphyses and punctate calcifications commonly present adjacent to the ossified ischial and pubic bones and less commonly in other locations. In late infancy and childhood the radiologic criteria include demineralization in all bones with slow maturation, flat vertebral bodies, short humeri and femora, metaphyseal flaring, especially in the distal humerus, proximal femur and proximal tibia, immature shape of pelvis, and disappearance of the punctate calcifications with advancing age. The histologic changes of the resting cartilage include areas of degenerating cartilage which had become partially calcified, cystic changes with severe disturbance of the maturation of the cartilage at the physeal plate, and the formation of cancellous bone directly on resting cartilage. Ultrastructural changes are characterized by degeneration of chondrocytes, delicate collagenous fibrils without visible periodicity, and the presence of flocculent material within greatly distended endoplasmic reticulum.Supported in part by USPHS/NIH Grants GM 15422, GM 20130, and 5 K04 HD 18982. Submitted as Paper No. 1977 from the University of Wisconsin Laboratory of Genetics.     

Kniest dysplasia is caused by dominant collagen II (COL2A1) mutations: Parental somatic mosaicism manifesting as Stickler phenotype and mild spondyloepiphyseal dysplasia

We describe two unrelated children with Kniest dysplasia, a severe autosomal dominant form of chondrodysplastic dwarfism associated with cleft palate, progressive arthropathy, myopia and retinal detachment. In the first patient the disorder was caused by a 28 base pair exon 12/intron 12 deletion in the gene coding for type II collagen. Her mother had mild abnormalities of the vertebral bodies and long bones compatible with abnormalities seen in Stickler arthro-ophthalmopathy. The second child had a transition of AG to GG at the 3 splice site of intron 20 of the COL2A1 gene. Her father had premature polyarthrosis interpreted as a sequela of mild spondyloepiphyseal dysplasia. Molecular studies revealed that the mother of the first and the father of the second child each had somatic mosaicism of the same mutation as their children. Heterozygous mutations of the gene coding for type II collagen can cause Kniest dysplasia, and somatic mosaicism for the same mutations can result in the Stickler phenotype or in mild spondyloepiphyseal dysplasia leading to premature polyarthrosis.     

Management of midgut volvulus with extensive necrosis by “patch,drain, and wait” in early infancy and childhood

Midgut volvulus with extensive intestinal necrosis in the newborn period and in early infancy and childhood presents a difficult therapeutic dilemma of how to control sepsis and preserve a maximum and life-sustaining amount of large and small intestine. This problem is similar to that faced in cases of necrotizing enterocolitis with extensive intestinal ischemia and necrosis. The successful use of the patch, drain, and wait approach in necrotizing enterocolitis suggested its potential usefulness in midgut volvulus with similarly extensive necrosis in early life [7]. The basic principles of this approach involve maximum bowel salvage by avoidance of both resection and enterostomy; extensive bilateral Penrose drainage of the peritoneal cavity to provide an exit for sepsis and debris for peritonitis control; and de facto enterostomies for potential enteric fistula capture, gastrostomy for upper gastrointestinal tract venting and decompression, and Broviac catheter placement for long-term hyperalimentation. Three cases involving the successful use of this approach are reported.     

Vertebral anomalies in Larsen's syndrome

The case of two sisters with Larsen's syndrome is presented. In addition to typical features of the syndrome, multiple coronal cleft vertebrae of the lumbar vertebral bodies were seen in both sibs. The extremities were conspicuously short.     

Perinatal lethal hypophosphatasia; Clinical,radiologic and morphologic findings

Clinical, radiographic and morphologic analysis of nineteen cases of perinatal (lethal) hypophosphatasia was performed. Three families each had two affected offspring. All of the patients had lethal short limb dwarfism with very soft calvaria. Other clinical findings included polyhydramnios, blue sclerae and spurs in the mid-portion of the forearms and lower legs. Considerable variability was found in the skeletal radiographs. In addition to the well known radiographic features such as generalized decrease in the size of ossified bones with some bones not ossified at all, other changes observed included: 1) marked variability in the amount of bone ossification; 2) variability between patients as to which bones were most severely affected; 3) unusually dense, round, flattened, butterfly shaped; and saggitally clefted vertebral bodies; 4) variability in femoral shape including chromosome like, campomelic like, and shortening with or without metaphyseal cupping or irregularities; 5) osteochondral projections (Bowdler spurs) of the midshaft of the fibula and ulna. Recognition of the marked clinical and radiographic variability in this autosomal recessive lethal skeletal dysplasia is important for accurate genetic counseling and prenatal diagnosis.     

Chondrodysplasia punctata in a nine-year-old girl presenting as “Unclassified Multiple Malformation Syndrome”

A girl with chondrodysplasia punctata who showed changes consistent with Unclassified Multiple Malformation Syndrome at the age of 9 years is presented. The disease could not have been recognised had not the neonatal films been presented.     

Intussusception of the catheter sheath: A nonemergency

Percutaneous balloon dilatation angioplasty is a common therapeutic modality in patients with congenital heart disease. We report three cases of the catheter sheath telescoping into the hub of the sheath after removal of the balloon catheter. Although initially it appeared as though the sheath was torn, in actuality it was intact. We report this problem so others can avoid needless searching and concern for the missing catheter tip.     

Shwachman-Diamond syndrome: Clinical,radiological and sonographic aspects

Six children with Shwachman-Diamond syndrome have been diagnosed and treated in our hospital since 1986. We describe the radiological and sonographic findings of this rare disease which is characterized by metaphyseal chondrodysplasia, neutropenia and pancreatic exocrine insufficiency. It presents with variable extremity shortening, cup deformation of the ribs, metaphyseal widening and hypoplasia of the iliac bones, and increased echogenicity of the pancreas without change in size. We discuss the differential diagnosis and review the literature.     

“Partial trisomy 22 and 11” due to a paternal 11;22 translocation associated with hirschsprung disease

The 11;22 translocation seems to be the most frequent, non-Robertsonian translocation in man. Approximately 50 cases with an unbalanced karyotype 47,XX (or XY),+der(22), t(11q;22q), due to a 3:1 meiotic disjunction in the parental translocation carrier, have been reported in the literature. We present an additional patient with that chromosome aberration, whose father was shown to be the translocation carrier. He presented with many of the more or less typical signs of the syndrome, but had an extraordinary additional finding, namely Hirschsprung disease. Although anal stenosis is a rather frequent finding in the syndrome, Hirschsprung disease has never been described in the literature. Furthermore the most important genetic and cytogenetic data on that chromosome aberration are given, including implications for genetic counselling.Abbreviation ASD atrial septal defect The author is recipient of a scholarship from the Verein zur Förderung der human-genetischen Beratung, 5300 Bonn, FRG     

The Rose Bengal test in neonatal cholestasis: Diagnostic and prognostic value

¹³¹I Rose Bengal (¹³¹IRB) studies were performed in 73 infants with extrahepatic biliary atresia (EHBA) and in 37 with intrahepatic cholestasis of various origins. Fecal ¹³¹IRB excretion of less than 10% (complete cholestasis) was observed in EHBA but also in some patients with either paucity of intrahepatic bile ducts (syndromatic type) or with -1-antitrypsin deficiency. Seventy one ¹³¹IRB tests were also performed 3 to 8 weeks postoperatively in children operated on for EHBA. Fecal ¹³¹IRB excretion more than 15% was present in 27 out of 34 cases who were later completely jaundice free and in only one out of 37 cases where no bile flow restoration occurred.These results indicate that complete cholestasis in infants can be observed in some types of intrahepatic cholestasis, as well as in EHBA, and show that a postoperative ¹³¹IRB test is a reliable means of predicting complete restoration of bile flow in EHBA.     

Amine im menschlichen Stuhl

Zusammenfassung Die p- und m-Tyraminausscheidung wurde quantitativ im Stuhl von Neugeborenen, Säuglingen und Schulkindern unter verschiedenen Kostformen untersucht. Der p-Tyramingehalt von normalen Säuglingsstühlen (Naßgewicht) lag zwischen 0,030–0,460 Mol/g Stuhl, der normaler Stühle von Schulkindern zwischen 0,005 und 0,102 Mol/g Stuhl. m-Tyramin ließ sich in Säuglingsstühlen nicht nachweisen. Die Konzentration im Stuhl von Schulkindern überschritt sicher nicht 0,008 Mol/g Stuhl.

---

Summary The excretion of para- and meta-tyramine in faeces was estimated in newborns, infants, and children during the application of various diets. The p-tyramine content of normal stools of infants (wet weight) amounted 0.030–0.460 moles per gr. faeces and that of children 0.005–0.102 moles per gr. m-Tyramine was not detected in the faeces of infants. If this substance is found at all in faeces of children it does not exceed 0.008 moles per gr. of faeces.

---

---

Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Unusual bone dysplasia featuring severe platyspondyly and vertebral “coronal cleft” in infancy,and changes of metaphyseal chondrodysplasia in childhood

This is the report of a boy who presented at birth with severe generalized platyspondyly, a vertebral “coronal cleft”, and an abnormal configuration of the pelvis with short and broad iliac and ischial bones and horizontal acetabular roofs. The rest of the skeleton was normal. In the ensuing years the vertebral bodies and pelvis assumed a near normal configuration, but the patient developed changes of metaphyseal chondrodysplasia in the long bones of the lower limbs with progressive shortness of stature.     

Radiological “metamorphosis” in a patient with severe congenital osteogenesis imperfecta

Congenital osteogenesis imperfecta (OI) was diagnosed by ultrasound in a 31-week-old fetus, and the diagnosis confirmed after delivery by caesarean section at week 36. The baby survived the neonatal period, but failed to thrive, had recurrent respiratory infections and ultimately died at 8 months. Cultured fibroblasts synthesized both normal type I collagen and unstable type I collagen harbouring a structural defect in the 1(I) cyanogen bromide-derived peptide number 8 (CB8) region of the molecule, indicating a heterozygous dominant mutation. A⁺ birth, the radiological picture was that of the thin bone-type of congenital OI (OI type IIB/III in the Sillence classification); at the age of 12 weeks ribs and long bones had undergone a marked expansion giving a very different picture, that of the thick bone-type congenital OI (OI type IIA). The mechanism responsible for this change in bone structure is not known, but fractures and callus formation are unlikely to be the only factors. Caution is needed in the interpretation of radiographs of newborns with OI for prognostic or genetic purposes.     

Intravenous administration of human IgG to newborn infants: changes in serum antibody levels to group B streptococci

A human IgG preparation was given intravenously to 36 newborn infants admitted to the neonatal intensive care unit because of suspected septicaemia. IgG was given as a single dose of 0.4 g/kg body weight. Patients serum was obtained immediately before and 30 min after terminating the infusion. Blood was also withdrawn 2 days after giving the IgG in eight of the infants. The sera were tested by radioimmunoassay for IgG antibody levels to surface antigens of group B streptococci (GBS) types Ia, Ib, II and III and to R-protein. The mean increases in anti-type Ia, Ib, II, III and R-protein antibodies 30 min after the end of infusion were 81%, 73%, 49%, 60% and 69% of the preinfusion levels, respectively. This was followed by a rapid decrease during the following 2 days to 25%–32% of the initial increases. Based on the above findings, a controlled trial of passive immunisation in the management of neonatal GBS septicaemia seems justified. The rapid decline in antibody levels would necessitate a second infusion 24 h after the initial immunoglobulin administration if the suspicion of septicaemia persists.Abbreviation GBS group B streptococci Supported by grants from Allmänna BB Minnesfond, the Expressen Prenatal Research Foundation, the Hartmann-Müller-Stiftung, the Herzog-Egli-Stiftung, the Swedish Medical Research Council (grant no. B83-16X-06559-01), and the Swiss National Science Foundation (grant no. 3.884-0.81)     

The value of the routine chest roentgenogram in the cardiological evaluation of infants and children. A prospective study

The value of the routine chest roentgenogram was studied in 284 patients, newly admitted to our paediatric outpatient department. Emergency patients were excluded from the study. In 141 cases the initial diagnosis after history, physical examination and ECG was no heart disease, while in 143 cases it was heart disease. After a follow up of up to 4 years, 170 children appeared to have no heart disease and 114 definite heart disease. In 7.7% of cases the chest roentgenogram made at the first visit to the outpatient department led to a change in policy, whereas in only 3.8% was the chest roentgenogram in someway helpful in establishing the correct diagnosis. Amongst those children with initial diagnosis of innocent murmur, the chest roentgenogram led to a diagnosis of heart disease in only 2.8% of cases. It is concluded that for the differentiation heart disease or no heart disease, a chest X-ray film is not indicated. In children with heart disease the chest X-ray film is also of little value, and is mostly to be used only for documentation.Partly presented at the Jahrestagung der deutschen Gesellschaft für pädiatrische Kardiologie, Düsseldorf, 1–2 Oktober 1984