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Biomedical subjects

J L Tolmie

Publications and source records attributed to J L Tolmie.

At least 37 records · Page 2Linked to original sources
PubMed1997

An autosomal recessive adducted thumb-club foot syndrome observed in Turkish cousins.

Male and female cousins, the offspring of consanguineous Turkish parents, have been affected by a hitherto unreported combination of problems comprising moderate to severe psychomotor developmental delay, ocular anterior chamber abnormality, facial dysmorphisms (broad, bossed forehead, late-closing fontanelle, telecanthus, downslanting palpebral fissures, posteriorly rotated ears, downturned angles of mouth), arachnodactyly and distal arthrogryposis with severely adducted thumbs and club feet. This striking phenotype has some similarities with the multiple pterygium syndrome (Escobar syndrome), but it most likely represents a distinct condition caused by an autosomal recessive gene defect.

Abnormalities, Multiple↗
PubMed1997

A novel pattern of oculocerebral malformation.

AIMS/BACKGROUND: To report a novel pattern of oculocerebral malformation related to the group of diseases characterised by cobblestone lissencephaly. METHODS: By means of a case report with specialist descriptions of the novel neuropathological and ophthalmic pathology features. RESULTS: The patient, born to healthy consanguineous parents, presented in the neonatal period with jaundice, convulsions, and macrocephaly. Computed tomography demonstrated hydrocephalus and abnormal cerebral gyration. Ophthalmic examination revealed severe myopia and segments of retinal atrophy. Cytogenetic investigation revealed a balanced reciprocal translocation (46,XX,t(5p11;19q13.1)) that was inherited from the mother and was present in several normal relatives. Mild short stature and profound mental handicap were evident. The child died aged 7 years. At necropsy the brain showed 'cobblestone' (type II) lissencephaly. Cerebellar cortical architecture was abnormal and the brain stem lacked cerebral peduncles, basis pontis, and pyramids. Biopsies of skeletal muscles were normal. The ocular abnormalities included discrete sectors of retina of varying thickness with disordered neuronal lamination and gliosis. The optic nerve was gliotic and contained few nerve fibres. The anterior iris surface was studded with cellular stromal nodules which appear to be melanocytic in nature. CONCLUSION: Retinal dysgenesis occurs in the group of syndromes with 'cobblestone lissencephaly', the best known being Walker-Warburg syndrome. In this case, relatively long survival, lack of muscular dystrophy, and novel ocular pathology distinguish it from the other diagnoses in this group of syndromes. We suggest this child was affected by a distinct and novel oculocerebral syndrome.

Abnormalities, Multiple↗
PubMed1997

Dominantly inherited cerebral dysplasia: arachnoid cyst associated with mild mental handicap in a mother and her son.

We report a mother and son who each presented in infancy with hypotonia and global developmental delay. Subsequently, in both subjects, mild mental handicap was diagnosed in association with temporal lobe arachnoid cysts. Mendelian inheritance of this phenotype seems likely and macroscopic cerebral dysplasia in general may be underdiagnosed in people with familial, mild mental handicap.

Adult↗
PubMed1997

Paternal uniparental disomy for chromosome 6 causes transient neonatal diabetes.

We report an infant with intrauterine growth retardation and transient neonatal diabetes who has paternal uniparental disomy for chromosome 6. The infant was not dysmorphic and had no congenital anomalies. To our knowledge, this is the third case of paternal uniparental disomy occurring in an infant with transient neonatal diabetes, thus confirming the association.

Chromosome Aberrations↗
PubMed1997

Expect the worse or hope for the best? Prenatal diagnosis of geleophysic dysplasia.

Geleophysic dysplasia is a rare, autosomal recessive disorder which causes disproportionate short stature associated with severe physical handicaps, but is compatible with survival into adulthood. We present a case, a first-born child, where genetic counselling difficulties arose following ultrasound recognition of short-limbed dwarfism in association with polyhydramnios and an initial incorrect prenatal diagnosis of lethal chondrodysplasia. After birth of the surviving affected infant, the parents had great difficulty accepting that there had been a prenatal misdiagnosis and they were greatly disappointed by our inability to predict the postnatal survival of an infant to whom no hope of life had previously been given. The correct diagnosis was not made until the proband was nearly 1 year old, and the true prognosis then became clearer. This experience underlines the relative ease of prenatal recognition of skeletal growth abnormalities compared with the considerable difficulties experienced in reaching a precise diagnosis. Thus, following prenatal diagnosis of unspecified chondrodysplasia when parents seek definite information about the prognosis, the temptation to be either overpessimistic or overoptimistic should be avoided.

Abnormalities, Multiple↗
PubMed1996

Simpson-Golabi-Behmel syndrome: genotype/phenotype analysis of 18 affected males from 7 unrelated families.

Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked overgrowth disorder recently shown to be caused by mutations in the heparan sulfate proteoglycan GPC3 [Pilia et al., Nat Genet; 12:241-247 1996]. We have used Southern blot analysis and polymerase chain reaction amplification of intra-exonic sequences to identify four new GPC3 mutations and further characterize three previously reported SGBS mutations. De novo GPC3 mutations were identified in 2 families. In general, the mutations were unique deletions ranging from less than 0.1 kb to more than 300 kb in length with no evidence of a mutational hot spot discerned. The lack of correlation between the phenotype of 18 affected males from these 7 families and the location and size of the GPC3 gene mutations suggest that SGBS is caused by a nonfunctional GPC3 protein.

Abnormalities, Multiple↗
PubMed1996

X-linked hydrocephalus masquerading as spina bifida and destructive porencephaly in successive generations in one family.

The authors report a case of X-linked hydrocephalus which presented as a destructive porencephaly. There was asymmetric dilatation of the ventricles of prenatal onset, and neuro-imagining studies were suggestive of infection or haemorrhage. The child was profoundly handicapped but did not have adducted thumbs. Two of his mother's brothers had been stillborn, and postmortem reports revealed that the diagnosis had been isolated hydrocephalus and not spina bifida as reported by the family. Despite serial ultrasound scans, recurrence of X-linked hydrocephalus in the mother's subsequent pregnancy was not detected until 26 weeks gestation, when the ventricles became grossly dilated. The diagnosis was confirmed in this family by identification of mutation within the L1CAM gene.

Diagnosis, Differential↗
PubMed1996

X-linked hydrocephalus masquerading as spina bifida and destructive porencephaly in successive generations in one family.

The authors report a case of X-linked hydrocephalus which presented as a destructive porencephaly. There was asymmetric dilatation of the ventricles of prenatal onset, and neuro-imagining studies were suggestive of infection or haemorrhage. The child was profoundly handicapped but did not have adducted thumbs. Two of his mother's brothers had been stillborn, and postmortem reports revealed that the diagnosis had been isolated hydrocephalus and not spina bifida as reported by the family. Despite serial ultrasound scans, recurrence of X-linked hydrocephalus in the mother's subsequent pregnancy was not detected until 26 weeks gestation, when the ventricles became grossly dilated. The diagnosis was confirmed in this family by identification of a mutation within the LICAM gene.

Brain↗
PubMed1996

Clinical and molecular cytogenetic (FISH) diagnosis of Williams syndrome.

Sixteen children and adolescents with a firm clinical diagnosis of Williams syndrome were investigated with the chromosome fluorescence in situ hybridisation (FISH) technique employing the elastin gene probe. In each case there was a fluorescent signal on one chromosome 7 homologue only, indicating elastin gene deletion. No deletion was demonstrated in another child in whom an earlier diagnosis of Williams syndrome was judged doubtful at review. Firm clinical diagnosis correlates with elastin gene deletion in 16/16 cases of Williams syndrome and detection of such hemizygosity by FISH constitutes a useful confirmatory diagnostic test.

Adolescent↗
PubMed1996

Familial Wolf-Hirschhorn syndrome resulting from a cryptic translocation: a clinical and molecular study.

We present three cousins who have normal karyotypes, despite having clinical features of Wolf-Hirschhorn syndrome. Fluorescence in situ hybridisation techniques confirmed that all three relatives were monosomic for the distal short arm of chromosome 4 and that a cryptic translocation involving chromosomes 4 and 11 was segregating within the family. Segregation analysis indicated that the risk of an affected child being born to a parent carrying the translocation was 15%. Molecular analysis showed that loci D4S111 and D4S115 were not deleted in the proband, thus excluding these loci from the "Wolf-Hirschhorn critical region". Surprisingly, DNA studies also suggested that the translocation breakpoint on chromosome 4 was within the region of a preexisting paracentric inversion.

Abnormalities, Multiple↗
PubMed1996

Holoprosencephaly in the west of Scotland 1975-1994.

Cases of holoprosencephaly which occurred in the west of Scotland over the past 20 years were ascertained from genetics, paediatric, and pathology department records. Fifty cases were identified of which 17 had an underlying cytogenetic abnormality. Of the remaining 33 cases, 26 were delivered after 28 weeks' gestation giving a birth prevalence of 1 in 26730. Twenty-one babies were liveborn and nine children are currently alive. All survivors are profoundly mentally retarded and most have seizures. Twenty-eight patients with non-chromosomal holoprosencephaly had a total of 23 sibs and three families were identified where there was either recurrence of holoprosencephaly (one family), a related cerebral malformation (one family), or mental handicap (one family) giving an overall recurrence risk for serious neurological disability of 12% (standard error 7%). We conclude that holoprosencephaly does not necessarily breed true and this observation should be taken into account when giving genetic counselling and attempting ultrasound prenatal diagnosis after the birth of an affected child.

Chromosome Aberrations↗
PubMed1996

Familial hemiplegic migraine in the west of Scotland: a clinical and genetic study of seven families.

OBJECTIVES: Clinical and genetic characterisation of families in the west of Scotland with familial hemiplegic migraine. METHODS: Families with familial hemiplegic migraine were identified via probands attending the regional paediatric neurology and child development centre. All available family members were assessed clinically and genetic linkage studies for the known familial hemiplegic migraine gene locus on chromosome 19 were carried out on three families. RESULTS: Seven unrelated kindreds with familial hemiplegic migraine were identified. Clinical information was obtained on 138 family members, 27 of whom fulfilled the International Headache Society criteria for familial hemiplegic migraine. Whereas the severity, duration, frequency, and temporal progression of acute hemiplegic migrainous attacks showed pronounced variability within and between families, and even in the same individual over time, no true clinical heterogeneity of the condition was apparent. Genetic linkage analysis gave results consistent with linkage to the familial hemiplegic migraine gene locus on chromosome 19p in one family. In the other two families, evidence against linkage was obtained. There was no significant clinical difference between these three families. CONCLUSIONS: This study provides characterisation of the clinical features of familial hemiplegic migraine in a British population. Significant variability was found in the frequency and character of migraine attacks within and between families, and no true clinical heterogeneity was identified. On the other hand, further evidence for genetic heterogeneity of the condition was found.

Adolescent↗
PubMed1995

Uniparental isodisomy for chromosome 16 in a growth-retarded infant with congenital heart disease.

We report a growth-retarded infant with congenital heart disease and maternal isodisomy for chromosome 16. Non-mosaic trisomy 16 was detected at mid-trimester chorionic villus sampling, performed because biochemical screening indicated an increased Down's syndrome risk. Further karyotyping analysis of the placenta, after delivery, showed a 50 per cent mosaic trisomy 16. The infant had an atrioventricular (A-V) canal defect, scoliosis, and several minor dysmorphic features. Although uniparental disomy for chromosome 16 has been reported previously, to our knowledge this is the first case of uniparental isodisomy for chromosome 16 which has been investigated with multiple DNA probes.

Abnormalities, Multiple↗
PubMed1995

The Aicardi-Goutières syndrome (familial, early onset encephalopathy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis).

Aicardi-Goutières syndrome (Mendelian inheritance in man Catalog No *225750) is an autosomal recessive encephalopathy which causes developmental arrest, intracerebral calcification, and white matter disease in the presence of chronic cerebrospinal fluid lymphocytosis, and a raised level of cerebrospinal fluid interferon-alpha (IFN-alpha). Diagnosis requires the presence of progressive encephalopathy with onset shortly after birth, and characteristic clinical neurological and neuroimaging signs together with chronic CSF lymphocytosis. The syndrome has superficial resemblance to the neurological sequelae of congenital infection, thus a rigorous search for microbiological and serological evidence of embryopathic infections should be carried out in each case.

Abnormalities, Multiple↗
PubMed1995

The prenatal exclusion test for Huntington's disease: experience in the west of Scotland, 1986-1993.

Information about the prenatal exclusion test for Huntington's disease (HD) has been given to an unselected series of couples who attended the genetic counselling clinic from 1986 onwards. Ten couples underwent 13 prenatal tests during this period with expressed intention of stopping a pregnancy if the result indicated a high risk (almost 50%) that the fetus carried the HD gene. Nine fetuses at nearly 50% risk of carrying the HD gene were identified but only six such pregnancies were terminated. In each of three high risk pregnancies which continued, the mother made a "final hour" decision not to undergo the scheduled, first trimester termination. In our experience, late reversal of a previous decision to undergo first trimester pregnancy termination for a genetic indication is uniquely frequent among couples who have undergone the prenatal exclusion test for HD.

Adult↗
PubMed1994

Simpson-Golabi-Behmel syndrome: disproportionate fetal overgrowth and elevated maternal serum alpha-fetoprotein.

Simpson-Golabi-Behmel (SGB) syndrome is an X-linked condition with pre- and postnatal overgrowth, characteristic facies, and visceral and skeletal anomalies. We report an affected male who presented at 16 weeks' gestation with elevated maternal serum alpha-fetoprotein (MSAFP). Fetal measurements at 20 and 31 weeks' gestation were disproportionate, with marked macrosomia but a low head to abdominal circumference ratio and normal femur length. Fetal overgrowth with elevated MSAFP may prove to be useful markers for the prenatal diagnosis of SGB syndrome.

Abnormalities, Multiple↗