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ABSTRACT: Deletions of chromosome 6q are rare. We report 3 new patients with 6q deletions. Case 1 is a male with an interstitial deletion [del(6)(q13q14.2)], hypotonia, speech delays, and minor anomalies. Case 2 is a male with an interstitial deletion [del(6)(q16.2q22.32)] and malformations, including truncus arteriosus and bilateral oligodactyly. Case 3 is a male with a terminal deletion [del(6)(q25.2)] with retinal pits, hydrocephalus, atrioventricular canal, and hydronephrosis. The findings in our patients and those from 57 previously reported cases demonstrated 3 phenotypic groups associated with 6q deletions. Group A [del(6)(q11-q16)] had a high incidence of hernias, upslanting palpebral fissures, and thin lips with lower frequency of microcephaly, micrognathia, and heart malformations. Group B [del(6)(q15-q25)] was associated with increased intrauterine growth retardation, abnormal respiration, hypertelorism, and upper limb malformations. Group C [del(6)(q25-qter)] was associated with retinal abnormalities, cleft palate, and genital hypoplasia. The only universal finding among all patients with 6q deletions was mental retardation. Other findings common to all 3 groups included ear anomalies (90%), hypotonia (82%), and postnatal growth retardation (68%).
American Journal of Medical Genetics 07/1997; 70(4):377-86.
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ABSTRACT: We studied the neurodevelopmental profile of infants and toddlers with oculo-auriculo-vertebral spectrum (OAV) and determined if certain physical manifestations were indicative of a poor neurodevelopmental prognosis. Twenty-four patients with OAV, aged birth to 57 months, were seen in the Department of Medical Genetics at Children's National Medical Center for multidisciplinary evaluations, including neurodevelopmental assessments. Fifty-eight percent of these children scored more than 2 standard deviations below the mean in at least one domain of development. There was no difference in developmental outcome of boys versus girls, children affected unilaterally on the right side versus left side, and those with severe clinical manifestations versus those with a milder form. Children with OAV and abnormal muscle tone had lower cognitive, gross motor, and expressive language scores (P = 0.05, P = 0.002, and P = 0.02, respectively). Those affected bilaterally had lower cognitive, fine motor, receptive language, and expressive language scores (P = 0.06, P = 0.03, P = 0.03, P = 0.02, respectively). Children with cervical spine abnormalities had lower cognitive, fine motor, and expressive language scores (P = 0.02, P = 0.04, and P = 0.04, respectively). We conclude that infants and toddlers with OAV are at increased risk for neurodevelopmental delay, especially those with abnormal muscle tone, bilateral involvement, and cervical vertebral anomalies. The complexity of the neurodevelopmental problems is strongly suggestive of central nervous system disturbances. Patients with OAV need comprehensive evaluation by a multidisciplinary team to define potential neurodevelopmental delays, allow for early intervention services, and promote an optimal developmental outcome.
American Journal of Medical Genetics 01/1996; 60(6):535-40.
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Clinical Biochemistry 09/1995; 28(4):470-3. · 2.08 Impact Factor
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ABSTRACT: To report the clinical history and laboratory evaluation of a patient presenting with lactic acidosis secondary to pyruvate carboxylase deficiency.
Enzyme analysis of cultured skin fibroblasts revealed 2-5% of normal pyruvate carboxylase activity. Although most patients with this condition die in early infancy, this child has survived to age 8-1/2 years, with only occasional episodes of metabolic acidosis, usually responding rapidly to intravenous hydration and bicarbonate. Despite having a seizure disorder and moderate mental retardation, he continues to thrive and make progress in his acquisition of motor and language skills. Of the 35 patients described in the literature with pyruvate carboxylase deficiency, only two other patients have lived beyond 5 years of age.
There does not seem to be a correlation of prolonged survival with residual pyruvate carboxylase activity on assay of cultured fibroblasts. Possible explanations for this patient's prolonged survival include tissue heterogeneity, increased residual enzyme activity in vivo, or partial stabilization of the enzyme by supplemental biotin.
Clinical Biochemistry 03/1995; 28(1):85-9. · 2.08 Impact Factor
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H J Stern
Annals of Clinical Biochemistry 10/1994; 31 ( Pt 5):410-9. · 2.17 Impact Factor
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ABSTRACT: Osteogenesis imperfecta is a heterogeneous group of disorders of type I collagen with both lethal and nonlethal forms. Prenatal sonographic findings in affected fetuses are variable and depend on the severity of the disease. Six cases of osteogenesis imperfecta in which prenatal sonography had been performed were reviewed. Two cases of lethal type II osteogenesis imperfecta revealed short femurs at 16 to 17 weeks' gestation with development of bowing and fractures by 19 weeks' gestation. Four fetuses with the nonlethal type III or IV had femoral bowing with or without shortening in the late second or third trimester with grossly normal mineralization. Fractures in this latter group did not develop until 1 to 12 months after delivery. Understanding the progressive nature and variability of osteogenesis imperfecta is crucial in the prenatal diagnosis and management of this disease.
Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 07/1994; 13(6):419-27. · 1.25 Impact Factor
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ABSTRACT: The invention of the polymerase chain reaction (PCR) technique for nucleic acid amplification has had a major impact on many diverse areas of both basic and clinical research. Since its inception in 1985, reports on a wide variety of applications for PCR have received much attention in scientific and medical literature. This technology has been shown to have wide applicability to the diagnosis of human disease, including such diverse areas as infectious diseases, genetic disorders, and cancer. This article presents a broad overview of the principles of PCR including generic concerns that must be addressed when using or designing PCR-based assays. The application of PCR-based assays for the diagnosis of genetic disorders and for infectious disease testing is also discussed.
Journal of the International Federation of Clinical Chemistry / IFCC 08/1993; 5(3):96-105.
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ABSTRACT: We report on 2 Mennonite sisters with a syndrome of sparse hair, osteopenia, mental retardation, minor facial abnormalities, joint laxity, and hypotonia. Their asymptomatic consanguineous parents (inbreeding coefficient F = 1/64) have 6 other offspring, 3 of whom died in infancy of type II osteogenesis imperfecta (OI), and 3 of whom are normal. We analyzed collagens synthesized by cultured fibroblasts from these 2 sisters and their parents and detected no major abnormalities. Results of chromosomal and metabolic evaluations including amino acid analysis of plasma, urine, and hair were unremarkable. A literature search and survey of a computerized syndrome identification database did not disclose an identical phenotype. The sisters bear superficial resemblance to several known syndromes which we excluded on clinical and/or biochemical grounds. We conclude that they represent a new autosomal recessive syndrome, distinct from type II OI and perhaps unique to the Mennonite population or to this particular family.
American Journal of Medical Genetics 09/1992; 43(6):983-8.
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ABSTRACT: Detailed clinical, ophthalmological, and molecular studies were performed on a multigeneration family in which there were many subjects with type 1 neurofibromatosis, a common autosomal dominant disorder. Affected family members displayed a wide range of clinical findings including, in two subjects, features seen in Noonan syndrome (triangular facies, downward slanting palpebral fissures, micrognathia, short stature, and learning disability). Subjects have been described previously whose features have overlapped with neurofibromatosis and Noonan syndrome, and it has been suggested that these persons might represent a separate condition. DNA haplotype analysis showed linkage of the neurofibromatosis phenotype seen in this family to the proximal long arm of chromosome 17 in the region where the type 1 neurofibromatosis gene has been mapped. These results imply that the Noonan phenotype seen in some patients with type 1 neurofibromatosis might be the result of variable or variant expression of the neurofibromatosis gene on chromosome 17. The possible role of non-specific factors, such as fetal hypotonia, in producing the neurofibromatosis-Noonan phenotype needs further investigation. The availability of closely linked and intragenic molecular markers for neurofibromatosis could potentially be useful in the diagnosis and characterisation of patients and families with atypical forms of neurofibromatosis.
Journal of Medical Genetics 04/1992; 29(3):184-7. · 6.36 Impact Factor
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ABSTRACT: Fryns syndrome is an autosomal recessive, genetically determined condition with variable expression, which includes abnormal facial features, diaphragmatic hernia, distal limb abnormalities, and malformations of the cardiovascular, gastrointestinal, genitourinary, and central nervous systems. Five cases of children with Fryns syndrome, including an example of familial recurrence and a case of long-term survival, are described. This report brings to 25 the number of cases reported in the literature and further serves to illustrate the clinical variability of this disorder.
Pediatrics 05/1990; 85(4):499-504. · 5.44 Impact Factor
