Biomedical subjects

R S Lachman

Publications and source records attributed to R S Lachman.

At least 73 records · Page 4Linked to original sources

PubMed1996

Occipital encephalocele and MURCS association: case report and review of central nervous system anomalies in MURCS patients.

The combination of MURCS association (Müllerian duct and renal agenesis, upper limb and rib anomalies) and occipital encephalocele occurred in a stillborn girl of 41 weeks gestation. The malformations are compatible with a defect in the organization of the paraxial mesoderm that gives rise to occipital, cervical, and thoracic somites and adjoining intermediate mesoderm. These structures contribute to the occipital bone, cervical spine, upper limbs, and urogenital system. Brain imaging may be useful in assessing MURCS patients, if cranial malformations prove to be clinically important in these individuals.

Abnormalities, Multiple↗

PubMed1995

Spondyloperipheral dysplasia.

We present a patient with spondyloperipheral dysplasia, a rare skeletal dysplasia which is characterized by vertebral body abnormalities (platyspondyly, end-plate indentations) and brachydactyly. Our patient also manifested a characteristic "pugilistic" face, sensorineural deafness and mental retardation. This chondroosseous dysplasia appears to be inherited as an autosomal dominant disorder. It appears that there is considerable clinical variability in spondyloperipheral dysplasia.

Adult↗

PubMed1995

Microdontia with severe microcephaly and short stature in two brothers: osteodysplastic primordial dwarfism with dental findings.

Two brothers from a black family had microcephaly, short stature, and generalized microdontia. Endocrine and chromosome studies were normal, and mild skeletal manifestations were present. The patients may represent a distinct dental-skeletal dysplasia, possibly osteodysplastic primordial dwarfism type II. Attention to dental manifestations in similar cases may be useful for classification.

Adolescent↗

PubMed1995

Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3.

Thanatophoric dysplasia (TD), the most common neonatal lethal skeletal dysplasia, affects one out of 20,000 live births. Affected individuals display features similar to those seen in homozygous achondroplasia. Mutations causing achondroplasia are in FGFR3, suggesting that mutations in this gene may cause TD. A sporadic mutation causing a Lys650Glu change in the tyrosine kinase domain of FGFR3 was found in 16 of 16 individuals with one type of TD. Of 39 individuals with a second type of TD, 22 had a mutation causing an Arg248Cys change and one had a Ser371Cys substitution, both in the extracellular region of the protein. None of these mutations were found in 50 controls showing that mutations affecting different functional domains of FGFR3 cause different forms of this lethal disorder.

Alleles↗

PubMed1995

Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene.

Pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) are dominantly inherited chondrodysplasias characterized by short stature and early-onset osteoarthrosis. The disease genes in families with PSACH and MED have been localized to an 800 kilobase interval on the short arm of chromosome 19. Recently the gene for cartilage oligomeric matrix protein (COMP) was localized to chromosome 19p13.1. In three patients with these diseases, we identified COMP mutations in a region of the gene that encodes a Ca++ binding motif. Our data demonstrate that PSACH and some forms of MED are allelic and suggest an essential role for Ca++ binding in COMP structure and function.

Achondroplasia↗

PubMed1995

Dominant mutations in the type II collagen gene, COL2A1, produce spondyloepimetaphyseal dysplasia, Strudwick type.

The chondrodysplasias are a heterogeneous group of disorders characterized by abnormal growth or development of cartilage. Current classification is based on mode of inheritance as well as clinical, histologic, and/or radiographic features. A clinical spectrum of chondrodysplasia phenotypes, ranging from mild to perinatal lethal, is due to defects in the gene for type II collagen, COL2A1. This spectrum includes Stickler syndrome, Kniest dysplasia, spondyloepiphyseal dysplasia congenita (SEDC), achondrogenesis type II, and hypochondrogenesis. Individuals affected with these disorders exhibit abnormalities of the growth plate, nucleus pulposus, and vitreous humor, which are tissues that contain type II collagen. The Strudwick type of spondyloepimetaphyseal dysplasia (SEMD) is characterized by disproportionate short stature, pectus carinatum, and scoliosis, as well as dappled metaphyses (which are not seen in SEDC). The phenotype was first described by Murdoch and Walker in 1969, and a series of 14 patients was later reported by Anderson et al. The observation of two affected sibs born to unaffected parents led to the classification of SEMD Strudwick as an autosomal recessive disorder. We now describe the biochemical characterization of defects in alpha 1(II) collagen in three unrelated individuals with SEMD Strudwick, each of which is due to heterozygosity for a unique mutation in COL2A1. Our data support the hypothesis that some cases, if not all cases, of this distinctive chondrodysplasia result from dominant mutations in COL2A1, thus expanding the clinical spectrum of phenotypes associated with this gene.

Adult↗

PubMed1995

A radiographic, morphologic, biochemical and molecular analysis of a case of achondrogenesis type II resulting from substitution for a glycine residue (Gly691-->Arg) in the type II collagen trimer.

The type II collagenopathies form a continuous spectrum of clinical severity, ranging from lethal achondrogenesis type II and hypochondrogenesis, through spondyloepiphyseal dysplasia, spondyloepimetaphyseal dysplasia and Kniest dysplasia to the Stickler syndrome and familial precocious osteoarthropathy at the mildest end of the spectrum. We have carried out a radiographic, morphologic, biochemical and molecular study in a case of achondrogenesis type II. Electron micrographs showed inclusion bodies of dilated rough endoplasmic reticulum in the chondrocytes and the presence of sparse collagen fibers in the cartilage matrix. Protein analysis of collagen from cartilage indicated posttranslational overmodification of the major cyanogen bromide peptides, and suggested a mutation near the carboxyl terminus of the type II collagen molecule. Analysis at the DNA level demonstrated that the phenotype was produced by a single base change (G-->C) that resulted in the substitution of glycine691 by arginine in the type II collagen triple helical domain. We confirm previous observations in three cases of hypochondrogenesis that glycine substitutions in the alpha 1(II) chain can result in a phenotype at the most severe end of the type II collagenopathy spectrum.

Abortion, Induced↗

PubMed1995

Genetic skeletal dysplasia in Thailand: the Siriraj experience.

Genetic skeletal dysplasias are a heterogeneous group of genetic disorders associated with abnormalities in the skeletal system frequently presenting with disproportionate short stature. There are over 100 distinct skeletal dysplasias which have been classified primarily on the basis of the clinical or radiographic characteristics. We have identified many genetic skeletal dysplasia disorders at Department of Pediatrics, Siriraj Hospital, Bangkok, Thailand. We have cases of achondroplasia, hypochondroplasia, pseudoachondroplasia, atelosteogenesis, pyknodysostosis, spondyloepiphyseal dysplasia (SED) congenita, spondylometaepiphyseal dysplasia (SMED), osteogenesis imperfecta type I, II and III, Ellis-van Creveld syndrome, cleidocranial dysostosis, thanatophoric dysplasia, rhizomelic chondrodysplasia punctata, trichorhinophalangeal syndrome, mucopolysaccharidosis I, II, IV and VI, mucolipidosis II, osteopetrosis, camptomelic dysplasia, metaphyseal dysplasia with spine involvement (Kozlowski type), Langer-Gideon syndrome and hypophosphatemic rickets. We have established a Genetic Skeletal Dysplasia Clinic at Siriraj Hospital since 1992, and see referrals from around the country. Genetic counseling is provided, including prenatal diagnosis and a multidisciplinary approach.

Bone Diseases, Developmental↗

PubMed1994

Microcephalic osteodysplastic dysplasia.

We present two patients with a distinct facial phenotype, short stature, brachydactyly, clubfoot deformities, cataracts, microcephaly, and normal intelligence. Similar radiographic abnormalities of the spine, long bones, hands, and feet were noted. These patients are similar to 2 males previously described by Saul and Wilson [1990: Am J Med Genet 35:388-393]. These 4 patients appear to have a unique skeletal dysplasia characterized by microcephaly, distinct facial phenotype, multisystem abnormalities, and short stature of postnatal onset.

Abnormalities, Multiple↗

PubMed1994

Fetal imaging in the skeletal dysplasias: overview and experience.

The skeletal dysplasias (osteochondrodysplasias) comprise a heterogeneous group of disorders that are characterized by generalized abnormalities of skeletal growth and development. Of approximately 125 well-described skeletal dysplasias, about 50 are clinically apparent and identifiable at birth. The prevalence of these dysplasias in the newborn is quite frequent and has been estimated to be between 3-4.5 per 10,000, and the overall frequency of skeletal dysplasias among perinatal deaths to be about 9 per 1,000. Over the past 23 years we have acquired an enormous experience in the International Skeletal Dysplasia Registry with skeletal dysplasias diagnosable at birth or earlier. More and more cases referred to the registry over the past 2 years have been diagnosed as abnormal by ultrasound during the second trimester. The results of our evaluation of almost 400 fetuses and stillborn babies with reference to detailed prenatal history and postmortem evaluation including radiographs, chondro-osseous morphology and even some biochemical and molecular studies are presented. The most common disorders diagnosed were osteogenesis imperfecta (OI), thanatophoric dysplasia, campomelic dysplasia and achondrogenesis type II. Twenty-two types of neonatally diagnosable skeletal dysplasias are discussed together with potential fetal (second trimester) ultrasound findings, the number of fetal ultrasound cases referred to this registry, the number of total cases of that disorder sent to our registry, and the inheritance pattern of that skeletal dysplasia. This information should prove helpful in the evaluation of future cases ascertained by ultrasonography in the second trimester.

Female↗

PubMed1994

A single amino acid substitution (G103D) in the type II collagen triple helix produces Kniest dysplasia.

Kniest dysplasia is a moderately severe chondrodysplasia phenotype that results from mutations in the gene for type II collagen, COL2A1. Characteristics of the disorder include a short trunk and extremities, mid-face hypoplasia, cleft palate, myopia, retinal detachment, and hearing loss. Recently, deletions of all or part of exon 12 have been identified in individuals with Kniest dysplasia, suggesting that mutations within this region of the protein may primarily result in the Kniest dysplasia phenotype. We used SSCP to analyze an amplified genomic DNA fragment containing exon 12 from seven individuals with Kniest dysplasia. An abnormality was identified in one patient. DNA sequence analysis demonstrated that the patient was heterozygous for a G to A transition that implied substitution of glycine103 of the triple helical domain by aspartate. The mutation was not observed in DNA from either of the clinically unaffected parents of the proband. Protein microsequencing demonstrated expression of the abnormal allele in cartilage. These data demonstrate that point mutations which result in single amino acid substitutions can produce Kniest dysplasia and further support the hypothesis that alteration of a domain, which includes the region encoded by exon 12, in the type II collagen protein leads to this disorder.

Amino Acid Sequence↗

PubMed1993

Radiological features in Brachmann-de Lange syndrome.

Brachmann-de Lange syndrome (BDLS) is a well-delineated disorder consisting variably of pre- and postnatal growth deficiency, microbrachycephaly, characteristic face, hypertrichosis, visceral anomalies, and limb defects consisting primarily of variable limb reduction defects, micromelia, and elbow abnormalities. The course is usually marked by initial hypertonicity, low-pitched weak cry, feeding problems, and behavioral problems with marked mental deficiency. In classical cases there is rarely any difficulty in making the diagnosis, but for mildly affected cases, it may be difficult to feel secure about the diagnosis. In an effort to increase the precision of diagnosis for mildly affected cases, we reviewed roentgenograms in 21 cases of Brachmann-de Lange syndrome, as well as previously published descriptions of the radiological manifestations. Unusual radiologic manifestations were related primarily to the limb anomalies, and these were often asymmetric. These manifestations included digital abnormalities, which ranged from acheiria to oligodactyly, hypoplasia of the thumb and first metacarpal, clinodactyly of the fifth finger, or ectrodactyly. Long bone abnormalities included ulnar a/hypoplasia, dysplasia of the radial head, or fusion of the elbow. When there was a single forearm bone, there was often fusion at the elbow and oligodactyly, which made it difficult to determine whether the radius or ulna was absent. Other radiologic manifestations included 13 ribs with precocious sternal fusion, and micrognathia. We suggest that these radiologic manifestations could increase diagnostic precision in mildly affected cases.

Child↗

PubMed1993

DOOR syndrome (deafness, onycho-osteodystrophy, and mental retardation): a new patient and delineation of neurologic variability among recessive cases.

We report the seventeenth case of the recessive form of the DOOR syndrome. The parents were Guatemalan and not known to be consanguineous. The patient had developmental delay, severe sensorineural deafness, and abnormal nails and phalanges in the hands and feet. Urinary 2-oxoglutarate excretion was normal. The patient was among a subset of DOOR syndrome patients without seizures in infancy. This observation may be useful in discussing the prognosis for newly identified cases.

Abnormalities, Multiple↗

PubMed1993

Fetal akinesia/hypokinesia sequence: prenatal diagnosis and intra-familial variability.

Intrauterine fetal movement plays a key role in normal embryonic and fetal development (Moessinger, 1983). When movement is absent or decreased, abnormal development takes place which can be appreciated in newborns and/or fetuses with the fetal akinesia/hypokinesia sequence. This sequence is caused by a number of heterogeneous entities which result in decreased fetal movements by the action of intrinsic or extrinsic factors. Prenatal diagnosis of the akinesia/hypokinesia sequence may be possible during the second trimester through the use of real-time ultrasonographic evaluation of fetal movement. We report a family with three consecutive affected pregnancies in which the prenatal presentation of this sequence varied. Based on the phenotypic findings of the three affected fetuses, we believe that although they superficially resemble those features found in the New-Laxova syndrome, they are probably affected with a distinctly different lethal form of akinesia/hypokinesia transmitted in an autosomal recessive fashion.

Abnormalities, Multiple↗

PubMed1993

Prenatal diagnosis of the skeletal dysplasias.

OBJECTIVE: We examined the accuracy of prenatal diagnosis of skeletal dysplasias and ways to refine this ability. STUDY DESIGN: A total of 226 fetuses and stillbirths referred for suspected skeletal dysplasia were evaluated. The fetal age, mode of ascertainment, and referring diagnosis were analyzed with regard to the final diagnosis. RESULTS: The leading mode of diagnosis was routine ultrasonography performed between 16 and 24 weeks' gestation. Twenty-two cases (9.7%) had previous sibs, parents, or cousins affected. The most common final diagnosis was osteogenesis imperfecta. In 15 cases (7%) the fetus did not appear to have a skeletal dysplasia or an obvious dysmorphic syndrome. CONCLUSIONS: Prenatal diagnosis of skeletal dysplasia can be made as early as 14 weeks. Most cases are sporadic. Fetal radiographs help in reaching an accurate diagnosis or at least in identifying the probable lethal disorders.

Bone Diseases, Developmental↗

PubMed1993

A new variant of lethal neonatal short-limbed platyspondylic dwarfism.

This article describes an unusual skeletal dysplasia in a male fetus diagnosed by ultrasound at 18 weeks of gestation. The clinical and radiologic findings resemble thanatophoric dysplasia. Histologic examination revealed abnormalities in the resting cartilage, physeal growth plate, and bone. The resting cartilage contained peculiar large chondrocytes with huge lacunae. The growth plate revealed absence of column formation and hypertrophic vacuolated chondrocytes extending far into the metaphyseal bone trabeculae. The bone was hypercellular with absence of lamellar bone. The cortical bone was scanty and woven. The histopathologic features are, therefore, unique and differ from all other well-recognized varieties of short-limbed platyspondylic dwarfism.

Bone and Bones↗

PubMed1992

Spondylometaphyseal dysplasia, Sedaghatian type.

In 1980 Sedaghatian described an Iranian infant who died shortly after birth. At autopsy, he was found to have subacute myocarditis, cortical necrosis of kidneys, and adrenal and pulmonary hemorrhage. His skeletal abnormalities included mild rhizomelic shortness of his limbs and platyspondylyl and "laciness" of the iliac wings. In 1987 Optiz et al. described another Iranian infant with a similar perinatal course and roentgenograms. This infant was born to first cousins, suggesting an autosomal recessive single gene defect. We report our findings of another infant with a lethal course.

Bone and Bones↗

PubMed1991

Radiological findings in Hallermann-Streiff syndrome: report of five cases and a review of the literature.

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.

Adolescent↗