Filamin a, periventricular nodular heterotopia, and West syndrome.
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Brain Diseases↗
Biomedical subjects
S P Robertson
Publications and source records attributed to S P Robertson.
Newborn screening: new developments, new dilemmas.
Scientific and technological advances are lending pressure to expand the scope of newborn screening. Whereas this has great potential for improving child health, it also challenges our current perception of such programmes. Standard newborn screening programmes are clearly justified by the fact that early detection and treatment of affected individuals avoids significant morbidity and mortality. However, proposals to expand the scope and complexity of such testing are not all supported by a similar level of evidence for unequivocal benefit. We argue that screening for genetic susceptibility to complex disorders is inherently different from standard screening and, while of potential value, must be considered separately from conventional testing.
Diabetes Mellitus↗
Mutations in FLNB cause boomerang dysplasia.
Boomerang dysplasia (BD) is a perinatal lethal osteochondrodysplasia, characterised by absence or underossification of the limb bones and vertebrae. The BD phenotype is similar to a group of disorders including atelosteogenesis I, atelosteogenesis III, and dominantly inherited Larsen syndrome that we have recently shown to be associated with mutations in FLNB, the gene encoding the actin binding cytoskeletal protein, filamin B. We report the identification of mutations in FLNB in two unrelated individuals with boomerang dysplasia. The resultant substitutions, L171R and S235P, lie within the calponin homology 2 region of the actin binding domain of filamin B and occur at sites that are evolutionarily well conserved. These findings expand the phenotypic spectrum resulting from mutations in FLNB and underline the central role this protein plays during skeletogenesis in humans.
Abnormalities, Multiple↗
Tufted apple bud moth (Lepidoptera: Tortricidae) management model for processing apples based on early season pheromone trap capture.
Sixteen years of archived tufted apple bud moth, Platynota idaeusalis (Walker), trap capture data were compared with archived fruit injury data collected at the Penn State University Fruit Research and Extension Center to define the relationship of trap capture to fruit injury. Pheromone trap capture until 15 June was the best predictor of fruit injury at harvest. Using the regression equation of fruit injury on early season trap capture, and other assumptions about insecticide cost and fruit yield, a management model was developed for apple growers in the Mid-Atlantic region. When the model was tested on archived trap capture and fruit injury data, the results indicated that a grower would lose money on average by always treating and save money on average by never treating. By using the model, a grower could expect to save more money than by never treating. The model showed sensitivity to fruit price, insecticide price, and fruit yield.
Animals↗
Dominant intermediate Charcot-Marie-Tooth neuropathy maps to chromosome 19p12-p13.2.
The hereditary disorders of peripheral nerve form one of the most common groups of human genetic diseases, collectively called Charcot-Marie-Tooth (CMT) neuropathy. Using linkage analysis we have identified a new locus for a form of CMT that we have called "dominant intermediate CMT" (DI-CMT). A genomewide screen using 383 microsatellite markers showed strong linkage to the short arm of chromosome 19 (maximum LOD score 4.3, with a recombination fraction (straight theta) of 0, at D19S221 and maximum LOD score 5.28, straight theta=0, at D19S226). Haplotype analysis performed with 14 additional markers placed the DI-CMT locus within a 16.8-cM region flanked by the markers D19S586 and D19S546. Multipoint linkage analysis suggested the most likely location at D19S226 (maximum multipoint LOD score 6.77), within a 10-cM confidence interval. This study establishes the presence of a locus for DI-CMT on chromosome 19p12-p13.2.
Charcot-Marie-Tooth Disease↗
Linkage of otopalatodigital syndrome type 2 (OPD2) to distal Xq28: evidence for allelism with OPD1.
Otopalatodigital syndrome type 1 (OPD1) is an X-linked semidominant condition characterized by malformations of the skeleton, auditory apparatus, and palate. Previous studies have established linkage to a 16-cM region of Xq27-q28. A proposed allelic variant of OPD1, termed "OPD2," is associated with a more severe, frequently lethal phenotype with visceral and brain anomalies in addition to skeletal, auditory, and palatal defects. We report linkage of the OPD2 phenotype to a 2-cM region of distal Xq28 in a Maori kindred, with a maximum multipoint LOD score of 3.31 between the markers DXS1073 and DXS1108. This provides support for allelism between OPD1 and OPD2 and reduces the size of the disease interval to 1.8-2.1 Mb. We also demonstrate that female carriers of this disorder exhibit skewed inactivation that segregates with the high-risk haplotype and may be inversely related to the severity with which they manifest features of the disorder.
Abnormalities, Multiple↗
Hypogonadotrophic hypogonadism in Roifman syndrome.
The combination of spondyloepiphyseal dysplasia, humoral immune deficiency, growth retardation, intellectual deficit and characteristic facial dysmorphism has recently been delineated as a discrete disorder thus far only reported in males. This report describes a fifth individual with co-existent hypogonadotrophic hypogonadism, thereby expanding the phenotype and possibly offering insight into the genetic aetiology of this condition.
Adult↗
Homozygous deletion of SHOX in a mentally retarded male with Langer mesomelic dysplasia.
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Adolescent↗
Macrocephaly--cutis marmorata telangiectatica congenita: report of five patients and a review of the literature.
Cutis marmorata telangiectatica congenita (CMTC) is a cutaneous disorder often accompanied by additional anomalies, most commonly segmental overgrowth. Recently a clinically discrete condition has been described comprising CMTC and congenital macrocephaly together with pre- and post-natal macrosomia, segmental overgrowth, central nervous system malformations, connective tissue abnormalities and intellectual handicap. We describe the natural history of macrocephaly-CMTC (M-CMTC) syndrome in a further five patients including the oldest reported patient, a 22 year old. The addition of our five patients brings the total number of reported patients to 28 and now makes it possible to more accurately delineate the phenotype and the frequency of clinical manifestations. We add some further clinical associations to those previously described, including anomalies of the growth of hair and teeth, neuronal migration defects, dislocated hips and stridor. We discuss potential genetic mechanisms that might account for the pleiotropic manifestations of this apparently rare segmental overgrowth disorder.
Abnormalities, Multiple↗
Congenital hypertrichosis, osteochondrodysplasia, and cardiomegaly: Cantú syndrome.
Cantú syndrome (hypertrichosis, osteochondrodysplasia, cardiomegaly) is a rare condition, previously reported in 13 patients. We report on two additional patients with this disorder. One of the patients had pulmonary hypertension of unknown cause which was responsive to steroid therapy. She also had unusual, deep plantar creases, not reported previously in Cantú syndrome. Autosomal recessive inheritance has been suggested previously on the basis of sib recurrence in one family and consanguinity in another. We have performed a segregation analysis based on all reported families to date; the data indicate autosomal recessive inheritance is unlikely. A new dominant mutation or microdeletion syndrome are more likely possibilities, sib recurrence possibly representing gonadal mosaicism.
Cardiomegaly↗
Oromandibular limb hypogenesis complex (Hanhart syndrome): a severe adult phenotype.
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Abnormalities, Multiple↗
An autosomal dominant or X-linked osteodysplastic disorder with severe cervical involvement.
A disorder affecting bone and cartilage growth is described in a mother and her 3-year-old son. A dysplastic process involving the vertebral bodies, most pronounced in the cervical region and leading to cervical dislocation in the first of these two patients, is the most significant complication of this disorder. This entity appears unrelated to other previously described skeletal dysplasias with cervical kyphosis as a major manifestation. This disorder is most likely autosomal dominant.
Adult↗
Sotos syndrome and cutis laxa.
Characteristics suggestive of connective tissue dysfunction have been described in Sotos syndrome and include joint hyperextensibility, pes planus, and a high arched palate. A variety of cutis laxa syndromes have also been described, some of them exhibiting mental retardation, but no reports have drawn an association with overgrowth or abnormal facies characteristic of Sotos syndrome. We report three patients with the anthropometric and dysmorphological appearance of classical Sotos syndrome in association with redundant skin folds, joint hypermobility, and, in two of the three, vesicoureteric reflux suggestive of a coexisting connective tissue disorder. All of the patients had a normal bone age suggesting that Sotos syndrome in its classically described form was not present and that this entity possibly reflects a related, perhaps allelic, condition.
Abnormalities, Multiple↗
Zimmermann-Laband syndrome in an adult. Long-term follow-up of a patient with vascular and cardiac complications.
Zimmermann-Laband syndrome (ZLS) is characterised by findings of coarse facial appearance, hepatosplenomegaly, and hirsutism often first observed in infancy, followed by the evolution during childhood of gingival fibromatosis, small joint hyperextensibility, and hypoplasia of the finger- and toenails. Intellectual deficit is variable. Some of these findings are suggestive of a storage disorder, but no biochemical defect has been identified. We report on a four decade follow-up of a male with ZLS who developed a cardiomyopathy and dilatation of the aortic root and arch, anomalies hitherto undescribed in this syndrome.
Abnormalities, Multiple↗
Cerebrospinal fluid shunts in the management of behavioural problems in Sanfilippo syndrome (MPS III).
UNLABELLED: Severe behavioural disturbance is a very common feature of Sanfilippo syndrome (mucopolysaccharidosis III, MPSIII), and one of the more difficult aspects of the disease to treat. We describe a series of six patients with MPS III who had cerebrospinal shunts inserted in an attempt to ameliorate behaviour that had proved refractory to conventional treatment. Symptoms improved significantly in all six but removal of the shunt was necessitated in one patient due to shunt blockage and infection. CONCLUSION: Our experience suggests cerebrospinal fluid shunting should be formally evaluated as an adjunct to conventional forms of treatment of extreme behavioural disturbance in MPS III.
Adolescent↗
Early childhood growth in ethnic groups predisposed to NIDDM: a prospective study.
Evidence is accumulating to suggest that the intrauterine environment may not only influence fetal growth and anthropometric indices at birth but also contribute to susceptibility to adult onset diseases such as non-insulin-dependent diabetes (NIDDM). We have followed up 77 out of 123 (65%) children at age 2 years 8 months derived from a population at high risk of NIDDM who were initially studied throughout pregnancy and birth to determine whether their weight, height, and measures of adiposity were predicted by maternal size, glycaemic control during pregnancy, or ethnicity. Adiposity was correlated with maternal pre-pregnancy weight and maternal serum triglyceride concentration. In contrast to the data gathered at birth, ethnic group did not predict any anthropometric variable except that South Asian children demonstrated faster weight gain in infancy compared to Polynesian or European subgroups.
Adult↗
The 4q-syndrome: delineation of the minimal critical region to within band 4q31.
A consistent phenotype has been associated with deletion of the distal long arm of chromosome 4. An invariant requirement for the phenotype in cases described so far has been the deletion of material from within band 4q31 but few other cases have been described that further aid the delineation of the minimum critical region sufficient for the expression of the phenotype. We report a child with a small interstitial deletion within band 4q31 who exhibits most of the features of the established 4q-phenotype.
Abnormalities, Multiple↗
Protein adsorption to poly(ether urethane ureas) modified with acrylate and methacrylate polymer and copolymer additives.
To understand better blood interactions with poly(ether urethane urea) (PEUU) materials, a radioimmunoassay and whole or diluted human plasma were used to characterize the presence of fibrinogen, immunoglobulin G, factor VIII/von Willebrand factor, Hageman factor (factor XII), and albumin on a PEUU formulation and on PEUU formulations modified with the amphiphilic additive Methacrol 2138F (co[diisopropylaminoethyl methacrylate (DIPAM)/decyl methacrylate] [3/1]), or with hydrophobic acrylate or methacrylate polymer or copolymer additives. The protein adsorption assay showed that PEUU films loaded or coated with Methacrol 2138F (Methacrol) or homopoly-DIPAM (h-DIPAM) adsorbed significantly lower amounts of the studied proteins than did either the base PEUU formulations or the PEUUs loaded with the more hydrophobic acrylate or methacrylate polymer additives. Experiments with Methacrol-loaded PEUUs, where the loading of Methacrol was varied from 0.25 wt% to 20.0 wt%, showed that the adsorption of each of the characterized proteins did not vary significantly throughout the Methacrol loading range, and that all Methacrol-loaded PEUU formulations adsorbed significantly lower amounts of the studied proteins than did the unloaded PEUU. Phase separation within the additive loaded PEUUs was characterized by scanning electron microscopy (SEM). The solubility parameters of the additives, as well as of the base PEUU, were calculated and used to interpret differences in phase separation of the additive modified PEUUs. The analysis showed that additives of lower solubility parameter phase-separated into fewer large microdroplets within the PEUU matrix. SEM analysis also showed that additive microdroplets were not present on the air side surface of loaded PEUUs. To explain the differences in protein adsorption to the air side of additive loaded PEUUs when compared to the base PEUU, it was assumed that the additives near this region of the solvent swollen PEUU matrix may have migrated to, at, or near the PEUU-air interface during film formation, creating an additive enriched PEUU surface region. Once at this surface region, it was suggested that dynamic surface reorientation in response to an aqueous medium ensured that the additives were able significantly to influence protein adsorption behavior only if they interacted with aqueous media more favorably than the PEUU.
Acrylates↗