Search tips
Search criteria

Results 1-25 (801061)

Clipboard (0)

Related Articles

1.  Redefined genomic architecture in 15q24 directed by patient deletion/duplication breakpoint mapping 
Human genetics  2009;126(4):589-602.
We report four new patients with a submicroscopic deletion in 15q24 manifesting developmental delay, short stature, hypotonia, digital abnormalities, joint laxity, genital abnormalities, and characteristic facial features. These clinical features are shared with six recently reported patients with a 15q24 microdeletion, supporting the notion that this is a recognizable syndrome. We describe a case of an ~2.6 Mb microduplication involving a portion of the minimal deletion critical region in a 15-year-old male with short stature, mild mental retardation, attention deficit hyperactivity disorder, Asperger syndrome, decreased joint mobility, digital abnormalities, and characteristic facial features. Some of these features are shared with a recently reported case with a 15q24 microduplication involving the minimal deletion critical region. We also report two siblings and their mother with duplication adjacent and distal to this region exhibiting mild developmental delay, hypotonia, tapering fingers, characteristic facial features, and prominent ears. The deletion and duplication breakpoints were mapped by array comparative genomic hybridization and the genomic structure in 15q24 was analyzed further. Surprisingly, in addition to the previously recognized three low-copy repeat clusters (BP1, BP2, and BP3), we identified two other paralogous low-copy repeat clusters that likely mediated the formation of alternative sized 15q24 genomic rearrangements via non-allelic homologous recombination.
PMCID: PMC3669685  PMID: 19557438
2.  Metacarpal index in Marfan's syndrome and in constitutional tall stature. 
Archives of Disease in Childhood  1994;70(2):149-150.
The metacarpal index (MCI) in 54 children with constitutional tall stature was mean (SD) 8.65 (0.8) and in 55 with Marfan's syndrome 9.15 (0.9). Indices in both groups showed arachnodactyly and differed from those found in normal individuals (< 7.9). Because the MCI is a poor discriminator patients with tall stature or clinical signs of arachnodactyly should be examined for additional signs of Marfan's syndrome or other hereditary disorders of connective tissue.
PMCID: PMC1029724  PMID: 8129443
3.  Further delineation of Nevo syndrome. 
Journal of Medical Genetics  1997;34(5):366-370.
Nevo syndrome is an autosomal recessive syndrome characterised by prenatal overgrowth, joint laxity, kyphosis, wrist drop, spindle shaped fingers, and volar oedema. Four children from two families have been reported previously. We report two further children from two unrelated Arab families from two different tribes. Both presented at birth with hypotonia, joint laxity, kyphosis, wrist drop, spindle shaped fingers, and volar oedema. Both have delayed motor development at the ages of 2 years 10 months and 3 months respectively. Cognitive development is normal in one, and the other case appears to be developing normally at 3 months of age. One has, in addition, a wide spinal canal on MRI of the spine indicating some degree of dural ectasia. This report brings the total number of children reported with this syndrome to six from four families; three of these families are Arab. This indicates that the gene for this syndrome is probably commoner in Arabs than in other populations.
PMCID: PMC1050942  PMID: 9152832
4.  Combined Bentall and modified Ravitch procedures in a patient with Marfan syndrome 
Marfan syndrome is an inherited, connective-tissue disorder transmitted as an autosomal dominant trait. Cardinal features of the disorder include tall stature, ectopia lentis, mitral valve prolapse, aortic root dilatation, and aortic dissection. Pectus excavatum may exist as an isolated lesion or in association with a genetic syndrome such as Marfan syndrome. We report the successful management of a simultaneous correction of pectus excavatum and the underlying cardiovascular diseases.
PMCID: PMC3590552  PMID: 23493844
Aortic aneurysm; Marfan syndrome; pectus excavatum
5.  Ehlers Danlos Syndrome: An Unusual Presentation You Need to Know about 
Case Reports in Pediatrics  2013;2013:764659.
The Ehlers Danlos syndromes (EDS) comprise a group of connective tissue disorders characterized by tissue fragility of the skin, ligaments, blood vessels and internal organs. Variable degrees of clinical severity and organ involvement are due to the molecular and biochemical heterogeneity of this group of disorders and have led to classification into well-characterized subtypes that are extending with the discovery of new genes and overlapping syndrome. Types include classical EDS (EDS I/II), hypermobility EDS (EDS III), vascular EDS (EDS IV), kyphoscoliosis EDS (EDS VI), arthrochalasia (EDS VIIA, B) and Dermatospraxis (EDS VIIC). Even to the well trained professional, the diagnosis of EDS remains a challenge due to overlapping symptoms and cases can remain without a well-defined classification. Life altering complications of this group of disorders include vascular and hollow organ rupture and ligamentous laxity leading to chronic dislocation with ensuing pain and long term disability. Patients initially present to the general practitioner who is expected to recognize the symptoms of EDS and to proceed with appropriate referral for definitive diagnosis and management to prevent devastating complications. In this paper, we describe a male with classical EDS complicated by devastating vascular and orthopedic events.
PMCID: PMC3670523  PMID: 23762718
6.  Determination of the molecular basis of Marfan syndrome: a growth industry 
Journal of Clinical Investigation  2004;114(2):161-163.
Although it has been known for more than a decade that Marfan syndrome — a dominantly inherited connective tissue disorder characterized by tall stature, arachnodactyly, lens subluxation, and a high risk of aortic aneurysm and dissection — results from mutations in the FBN1 gene, which encodes fibrillin-1, the precise mechanism by which the pleiotropic phenotype is produced has been unclear. A report in this issue now proposes that loss of fibrillin-1 protein by any of several mechanisms and the subsequent effect on the pool of TGF-β may be more relevant in the development of Marfan syndrome than mechanisms previously proposed in a dominant-negative disease model. The model proposed in this issue demonstrates several strategies for clinical intervention.
PMCID: PMC449756  PMID: 15254580
7.  A new variant of spondylometaphyseal dysplasia with autosomal dominant mode of inheritance. 
Journal of Medical Genetics  1982;19(2):104-109.
Clinical and radiographic evaluation of an infant boy and his father revealed findings suggesting a new variant of spondylometaphyseal dysplasia with an apparently autosomal dominant mode of inheritance. The main clinical findings included short stature and marked ligamentous laxity in the infant. X-ray findings included severe and peculiar multiple metaphyseal involvement and striking vertebral undermineralisation in the infant, and platyspondyly in the father. However, all the epiphyses were normal. Laboratory studies were essentially normal except for an extremely raised serum alkaline phosphatase in the infant. The uniqueness of these findings suggests a new variant of the spondylometaphyseal dysplasias, distinct from the cases described initially by Kozlowski et al and subsequent investigators.
PMCID: PMC1048838  PMID: 7077620
8.  Evidence for anticipation in Beckwith–Wiedemann syndrome 
European Journal of Human Genetics  2013;21(12):1344-1348.
Classical Beckwith–Wiedemann syndrome (BWS) was diagnosed in two sisters and their male cousin. The children's mothers and a third sister were tall statured (178, 185 and 187 cm) and one had mild BWS features as a child. Their parents had average heights of 173 cm (mother) and 180 cm (father). This second generation tall stature and third generation BWS correlated with increased methylation of the maternal H19/IGF2-locus. The results were obtained by bisulphite treatment and subclone Sanger sequencing or next generation sequencing to quantitate the degree of CpG-methylation on three locations: the H19 promoter region and two CTCF binding sites in the H19 imprinting control region (ICR1), specifically in ICR1 repeats B1 and B7. Upon ICR1 copy number analysis and sequencing, the same maternal point variant NCBI36:11:g.1979595T>C that had been described previously as a cause of BWS in three brothers, was found. As expected, this point variant was on the paternal allele in the non-affected grandmother. This nucleotide variant has been shown to affect OCTamer-binding transcription factor-4 (OCT4) binding, which may be necessary for maintaining the unmethylated state of the maternal allele. Our data extend these findings by showing that the OCT4 binding site mutation caused incomplete switching from paternal to maternal ICR1 methylation imprint, and that upon further maternal transmission, methylation of the incompletely demethylated variant ICR1 allele was further increased. This suggests that maternal and paternal ICR1 alleles are treated differentially in the female germline, and only the paternal allele appears to be capable of demethylation.
PMCID: PMC3831082  PMID: 23572028
Beckwith–Wiedemann syndrome; anticipation; imprinting; H19; IGF2
9.  Congenital contractural arachnodactyly (Beals syndrome) 
Congenital contractural arachnodactyly (Beals syndrome) is an autosomal dominantly inherited connective tissue disorder characterized by multiple flexion contractures, arachnodactyly, severe kyphoscoliosis, abnormal pinnae and muscular hypoplasia. It is caused by a mutation in FBN2 gene on chromosome 5q23. Although the clinical features can be similar to Marfan syndrome (MFS), multiple joint contractures (especially elbow, knee and finger joints), and crumpled ears in the absence of significant aortic root dilatation are characteristic of Beals syndrome and rarely found in Marfan syndrome. The incidence of CCA is unknown and its prevalence is difficult to estimate considering the overlap in phenotype with MFS; the number of patients reported has increased following the identification of FBN2 mutation. Molecular prenatal diagnosis is possible. Ultrasound imaging may be used to demonstrate joint contractures and hypokinesia in suspected cases. Management of children with CCA is symptomatic. Spontaneous improvement in camptodactyly and contractures is observed but residual camptodactyly always remains. Early intervention for scoliosis can prevent morbidity later in life. Cardiac evaluation and ophthalmologic evaluations are recommended.
PMCID: PMC1524931  PMID: 16740166
10.  Painful Hip Leading to the Diagnosis of MEN 2B Syndrome 
Case Reports in Endocrinology  2012;2012:567060.
Context. MEN 2B syndrome is characterized by the presence of medullary thyroid cancer, pheochromocytoma, mucosal neuromas, marfanoid features, and skeletal abnormalities like kyphoscoliosis, joint laxity, pes cavus, and slipped capital femoral epiphysis (SCFE) in a minority; we present the case of a young female who was brought to medical attention due to painful hip because of SCFE. Case Report. A 16-year-old female presented to orthopedics out-patient department (OPD) with complaints of pain around the left hip and walking with a limp for the last two months. MRI of hip confirmed the presence of SCFE of the left hip. General examination detected thyroid swelling which was found to be a medullary thyroid cancer and imaging of abdomen confirmed the presence of bilateral pheochromocytoma, also present were neuromas of tongue and lips. Thus, a diagnosis of MEN 2B syndrome was made. Conclusion. SCFE can sometimes be the presenting feature of MEN 2B syndrome. Physicians should keep this in mind as it can lead to early diagnosis of a potentially lethal illness.
PMCID: PMC3513729  PMID: 23227371
11.  Congenital cutis laxa with retardation of growth and development. 
Journal of Medical Genetics  1987;24(9):556-561.
Seven patients with congenital cutis laxa are presented. The associated features include developmental delay, joint laxity, wide anterior fontanelle, growth retardation, dental caries, and osteopenia. The heterogeneity and inheritance of congenital cutis laxa are discussed. This particular syndrome appears distinct and is likely to be autosomal recessive in view of the two brother-sister sib pairs in this report.
PMCID: PMC1050268  PMID: 3669050
12.  Osteoporosis-pseudoglioma syndrome with congenital heart disease: a new association. 
Journal of Medical Genetics  1988;25(1):32-36.
We report a sibship of two brothers and one sister with the osteoporosis-pseudoglioma syndrome and congenital heart disease. They presented in infancy with visual impairment and psychomotor retardation. Major features included bilateral cataracts, generalised osteopenia, severe platyspondyly, borderline mental retardation, muscular hypotonia, joint laxity, and ventricular septal defect. Parental consanguinity and affected sibs of both sexes strongly suggested autosomal recessive inheritance. Analysis of the present and previously reported cases showed a wide range of interfamilial variability which may point to the existence of multiple allelism or genetic heterogeneity in this syndrome.
PMCID: PMC1015419  PMID: 3351889
13.  Anesthesia for a patient of acromesomelic dysplasia with associated hydrocephalus, Arnold Chiari malformation and syringomyelia 
Acromesomelic dysplasias are autosomal recessive osteochondrodysplasias. Acromesomelic dysplasia Maroteaux-type (AMDM), also known as St Helena dysplasia, is of two types: The classical and the mild variety. About 50 cases of AMDM have been reported till date, most of them being the classical variety. There is scarcity of literature on anesthesia for such patients. We are reporting a case of general anesthetic management of AMDM, associated with hydrocephalus, Arnold Chiari malformation type-1 and syringomyelia. The patient was a 10-year-old short-statured boy who presented with symptomatic thoracic kyphoscoliosis, gibbus deformity and back pain. On examination, there was no neurological deficit. Radiology revealed thoracic kyphoscoliosis, mild ventriculomegaly and upper cervical syringomyelia. The patient underwent posterior fossa decompression in the prone position under general anesthesia. We will discuss the anesthetic considerations for such patients and review the pertinent literature.
PMCID: PMC3819856  PMID: 24249999
Acromesomelic dysplasia; arnold chiari malformation; osteochondrodysplasia; short stature; syringomyelia
14.  Phenotypic variability of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA): clinical, molecular and biochemical delineation 
The kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA) (OMIM 225400) is a rare inheritable connective tissue disorder characterized by a deficiency of collagen lysyl hydroxylase 1 (LH1; EC due to mutations in PLOD1. Biochemically this results in underhydroxylation of collagen lysyl residues and, hence, an abnormal pattern of lysyl pyridinoline (LP) and hydroxylysyl pyridinoline (HP) crosslinks excreted in the urine. Clinically the disorder is characterized by hypotonia and kyphoscoliosis at birth, joint hypermobility, and skin hyperelasticity and fragility. Severe hypotonia usually leads to delay in gross motor development, whereas cognitive development is reported to be normal.
We describe the clinical, biochemical and molecular characterisation, as well as electron microscopy findings of skin, in 15 patients newly diagnosed with this rare type of Ehlers-Danlos syndrome.
Age at diagnosis ranged from 5 months to 27 years, with only 1/3 of the patients been diagnosed correctly in the first year of life. A similar disease frequency was found in females and males, however a broad disease severity spectrum (intra- and interfamilial), independent of molecular background or biochemical phenotype, was observed. Kyphoscoliosis, one of the main clinical features was not present at birth in 4 patients. Importantly we also noted the occurrence of vascular rupture antenatally and postnatally, as well as developmental delay in 5 patients.
In view of these findings we propose that EDS VIA is a highly variable clinical entity, presenting with a broad clinical spectrum, which may also be associated with cognitive delay and an increased risk for vascular events. Genotype/phenotype association studies and additional molecular investigations in more extended EDS VIA populations will be necessary to further elucidate the cause of the variability of the disease severity.
PMCID: PMC3135503  PMID: 21699693
15.  Assessment of bone in Ehlers Danlos syndrome by ultrasound and densitometry 
Annals of the Rheumatic Diseases  1998;57(10):630-633.
OBJECTIVE—Ehlers Danlos syndrome (EDS) is an inherited disorder of connective tissue characterised by hyperextensible skin, joint laxity, and easy bruising. There are phenotypic similarities with osteogenesis imperfecta, but in EDS a tendency to fracture or altered bone mass has not previously been considered to be a cardinal feature.
METHOD—This case-control design study investigates whether 23 patients with EDS had differences in fracture rates, bone mass, and calcaneal ultrasound parameters compared with age and sex matched controls.
RESULTS—23 cases of EDS (mean (SD) age 38.5 (15.5)) were compared with 23 controls (mean age 37.8 (14.5)). A significant reduction in bone density measured by dual energy x ray absorptiometry was found at the neck of femur by 0.9 SD, p = 0.05, and lumbar spine by 0.74 SD, p = 0.02. At the calcaneum, broad band ultrasound attenuation and speed of sound were significantly reduced compared with controls by 0.95 SD (p = 0.004) and 0.49 SD (p = 0.004) for broad band ultrasound attenuation and speed of sound respectively. Broad band ultrasound attenuation and speed of sound remained significantly reduced after adjusting for bone mineral density (BMD). After adjusting for functional status (HAQ), age and sex, hypermobility was inversely correlated with broad band ultrasound attenuation and SOS, but not BMD at hip or spine. Previous fracture was 10 times more common in EDS (p < 0.001), with 86.9% of patients reporting a total of 47 low impact fractures, compared with 8.7% of controls.
CONCLUSION—This study has identified a tendency of EDS patients to fracture, have low bone mass and abnormal bone structure. The aetiology is likely to be multifactorial, with an inherited structural element, accentuated by immobility or reduced exercise. This is one of the first clinical studies to suggest ultrasound can detect structural differences in bone, independent of dual energy x ray absorptiometry.

 Keywords: bone density; quantitative ultrasound; fracture, Ehlers Danlos syndrome
PMCID: PMC1752482  PMID: 9893576
16.  Fibrillin-1 Mutations Causing Weill-Marchesani Syndrome and Acromicric and Geleophysic Dysplasias Disrupt Heparan Sulfate Interactions 
PLoS ONE  2012;7(11):e48634.
The extracellular glycoprotein fibrillin-1 forms microfibrils that act as the template for elastic fibers. Most mutations in fibrillin-1 cause Marfan syndrome with severe cardiovascular and ocular symptoms, and tall stature. This is in contrast to mutations within a heparin-binding TB domain (TB5), which is downstream of the arg-gly-asp cell adhesion domain, which can cause Weill-Marchesani syndrome (WMS) or Acromicric (AD) and Geleophysic Dysplasias (GD). WMS is characterized by short limbs, joint stiffness and ocular defects, whilst fibrillin-1 AD and GD have severe short stature, joint defects and thickened skin. We previously showed that TB5 binds heparin. Here, we show that the corresponding region of fibrillin-2 binds heparin very poorly, highlighting a novel functional difference between the two isoforms. This finding enabled us to map heparin/heparan sulfate binding to two sites on fibrillin-1 TB5 using a mutagenesis approach. Once these sites were mapped, we were able to investigate whether disease-causing mutations in this domain disrupt binding to HS. We show that a WMS deletion mutant, and five AD and GD point mutants all have disrupted heparin binding to TB5. These data provide insights into the biology of fibrillins and the pathologies of WMS, AD and GD.
PMCID: PMC3487758  PMID: 23133647
17.  Assessment of the relationship between joint laxity and migration of the hip in children with Down syndrome 
The aim of this cross-sectional cohort study is to describe the incidence of joint laxity and the correlation between joint laxity and radiological migration of the hip in children with Down syndrome.
Sixty-five children (2–19 years) with Down’s syndrome were examined for joint laxity. For each subject, laxity scores for joints were carried out with the Bulbena method. Plane pelvic radiographs were used to determine the migration of the hip, according to Reimer’s migration index.
In this study, 26 out of 65 children with Down’s syndrome (40 %) were diagnosed with general joint laxity. On the radiographs of the hips we found a mean Reimer’s Migration Index of 5.2 % for all the subjects. Children with general joint laxity showed a lower Reimer’s Migration Index (2.1 %). No significant correlation was found between general joint laxity and migration of the hip.
This study showed no relationship between joint laxity and migration of the hip in children with Down’s syndrome. This implicates that we were not able to prove that joint laxity is the major factor in developing hip migration in children with Down’s syndrome.
PMCID: PMC3468730  PMID: 24082952
Down’s syndrome; Children; Joint laxity; Hip dysplasia; Migration of the hip
18.  Computer-aided preoperative planning in knee osteotomy. 
It has been demonstrated that osteoarthritis (OA) is activity related and may worsen when joint contact stress becomes excessive due to overloading. Hence, joint alignment and loading are considered to be the key biomechanical determinants for OA. The initiation of pathologic changes in the knee has been described by the mechanism termed, "vicious cycle" in which joint axial malalignment creates excessive stresses to the localized joint cartilage/subchondral bone regions and the surrounding soft tissue which in turn produces more laxity and joint deformity and thus repeats the cyclic degradation mechanism. If this degenerative cycle can be broken with joint alignment surgery such as osteotomy, a procedure to realign the knee joint and thus redistribute joint forces applied to each compartment, performed properly and at the appropriate time, the osteoarthritic disease process can be decelerated and even reversed. The main goals of this paper are to emphasize the importance of accurate preoperative planning for osteotomy in order to properly correct joint alignment, and to justify the application of an existing computer program, OASIS (Osteotomy Analysis and Simulation Software) using plain radiographs to perform appropriate surgical planning. Normal subjects and knee osteotomy patients were studied to establish a database for the purpose of establishing the utility and efficacy of the presently proposed concept. We wish to rationalize knee osteotomy as a preferred and cost-effective treatment for patients with early symptoms of OA in the knee. This paper presents a new concept of preoperative planning for knee osteotomy based on the underlying etiology of the disease and biomechanical viewpoint with strong emphasis on surgical treatment rationales. The established principles in this paper can be applied to other joints of the body and will help implement preventive measures and other non-surgical means to manage patients with axial malalignment or early degenerative changes.
PMCID: PMC2329085  PMID: 7634043
19.  Identifying Multiplanar Knee Laxity Profiles and Associated Physical Characteristics 
Journal of Athletic Training  2012;47(2):159-169.
A single measure of knee laxity (ie, measurement of laxity in a single plane of motion) is probably inadequate to fully describe how knee joint laxity is associated with anterior cruciate ligament injury.
To characterize interparticipant differences in the absolute and relative magnitudes of multiplanar knee laxity (ie, sagittal, frontal, and transverse planes) and examine physical characteristics that may contribute to these differences.
Descriptive laboratory study.
University research laboratory.
Patients or Other Participants:
140 participants (90 women, 50 men).
Main Outcome Measure(s):
Using cluster analysis, we grouped participants into distinct multiplanar knee laxity profiles based on the absolute and relative magnitudes of their anterior knee laxity (AKL), genu recurvatum (GR), and varusvalgus (VV) and internal-external rotation (IER) knee laxity. Using multinomial logistic regression, we then examined associations between the different laxity profile clusters and physical characteristics of sex, age, activity level, general joint laxity, body mass index, thigh strength, and 8 measures of lower extremity anatomical alignment.
Six clusters were identified: low (LOW), moderate (MOD) and high (HIGH) laxity overall and disproportionally higher VV/IER (MODVV/IER), GR (HIGHGR), and AKL (HIGHAKL) laxity. Once all other physical characteristics were accounted for, the LOW cluster was more likely to be older, with longer femur length. Clusters with greater magnitudes of VV and IER laxity were more likely to be younger and to have lower body mass index, smaller Q-angle, and shorter femur length (MOD, HIGH, MODVV/IER) and less thigh strength (HIGH). The HIGHGR cluster was more likely to be female and to have a smaller tibiofemoral angle and longer femur length. The HIGHAKL cluster was more likely to have greater hip anteversion and navicular drop.
The absolute and relative magnitudes of a person's multiplanar knee laxity are not always uniform across planes of motion and can be influenced by age, body composition, thigh strength, and structural alignment. Except in HIGHGR, sex was not a significant predictor of cluster membership once other physical characteristics were taken into account.
PMCID: PMC3418127  PMID: 22488281
hypermobility; anterior cruciate ligament injury risk factors; body composition; strength; lower extremity alignment; age; sex
20.  Evaluating tall children. 
Canadian Family Physician  1995;41:457-468.
The causes of tall stature are numerous; genetic tall stature and constitutional tall stature are the most common. Diagnosis can usually be established from the history and physical examination. An estimation of bone age can help to confirm diagnosis and to determine the child's growth potential. No treatment is usually necessary. Hormonal therapy can be considered for individuals for whom the predicted height is excessive if the psychosocial and medical advantages outweigh the risks of treatment.
PMCID: PMC2148014  PMID: 7773029
21.  Benign joint hypermobility syndrome among children with inguinal hernia 
Benign joint hypermobility syndrome (BJHS) is a disorder due to laxity of supporting connective tissue of joints. Inguinal hernia is also proposed due to weak supporting tissue that may be a clinical presentation of a more widespread problem of connective tissue.
Materials and Methods:
In a cross-sectional study, prevalence of benign hypermobility joint syndrome (BHJS) was assessed among 100 children aged 2-12 year admitted with inguinal hernia during 2010-2011.
BJHS (Beighton score ≥ 4) were detected in most of children (92%) with inguinal hernias.
BHJS amongst this population was substantially greater than reported prevalence in healthy children and due to subsequent clinical significances; it is worthy to screen such patient s for BHJS.
PMCID: PMC3897077  PMID: 24497864
Inguinal hernia; joint hypermobility; pediatric
22.  Bilaterally Asymmetric Effects of Quantitative Trait Loci (QTLs): QTLs That Affect Laxity in the Right Versus Left Coxofemoral (Hip) Joints of the Dog (Canis familiaris) 
In dogs hip joint laxity that can lead to degenerative joint disease (DJD) is frequent and heritable, providing a genetic model for some aspects of the human disease. We have used Portuguese water dogs (PWDs) to identify Quantitative trait loci (QTLs) that regulate laxity in the hip joint.A population of 286 PWDs, each characterized by ca. 500 molecular genetic markers, was analyzed for subluxation of the hip joint as measured by the Norberg angle, a quantitative radiographic measure of laxity. A significant directed asymmetry was observed, such that greater laxity was observed in the left than the right hip. This asymmetry was not heritable. However, the average Norberg angle was highly heritable as were the Norberg angles of either the right or left hips. After correction for pedigree effects, two QTLs were identified using the metrics of the left and right hips as separate data sets. Both are on canine chromosome 1 (CFA1), separated by about 95 Mb. One QTL, associated with the SSR marker FH2524 was significant for the left, but not the right hip. The other, associated with FH2598, was significant for the right but not the left hip. For both QTLs, some extreme phenotypes were best explained by specific interactions between haplotypes.
PMCID: PMC2778498  PMID: 14708095
quantitative trait loci (QTLs); dog; hip laxity; bilateral asymmetry; Norberg angle; Canine genetics; hip dysplasia
23.  Connective tissue dysplasia in five new patients with NF1 microdeletions: further expansion of phenotype and review of the literature 
Approximately 5% of patients with neurofibromatosis type 1 (NF1) have deletions of the entire NF1 gene. The phenotype usually includes early onset, large number of neurofibromas, presence of congenital anomalies, cognitive deficiency, and variable dysmorphic features and growth abnormalities. Connective tissue abnormalities are not generally recognised as a part of NF1 microdeletion syndrome, but mitral valve prolapse, joint laxity, and/or soft skin on the palms have been reported in a few patients. We describe clinical findings in six newly diagnosed patients with NF1 microdeletions, five of whom presented with connective tissue abnormalities. A literature review of the clinical findings associated with NF1 microdeletion was also performed. Our report confirms that connective tissue dysplasia is common in patients with NF1 microdeletions. Given the potential for associated cardiac manifestation, screening by echocardiogram may be warranted. Despite the large number (>150) of patients with known NF1 microdeletions, the clinical phenotype remains incompletely defined. Additional reports of patients with NF1 microdeletions, including comprehensive clinical and molecular information, are needed to elucidate possible genotype–phenotype correlation.
PMCID: PMC2603036  PMID: 16467218
neurofibromatosis type 1; microdeletion; connective tissue dysplasia
24.  Lujan-Fryns syndrome (mental retardation, X-linked, marfanoid habitus) 
The Lujan-Fryns syndrome or X-linked mental retardation with marfanoid habitus syndrome is a syndromal X-linked form of mental retardation, affecting predominantly males. The prevalence is not known for the general population. The syndrome is associated with mild to moderate mental retardation, distinct facial dysmorphism (long narrow face, maxillary hypoplasia, small mandible and prominent forehead), tall marfanoid stature and long slender extremities, and behavioural problems. The genetic defect is not known. The diagnosis is based on the presence of the clinical manifestations. Genetic counselling is according to X-linked recessive inheritance. Prenatal testing is not possible. There is no specific treatment for this condition. Patients need special education and psychological follow-up, and attention should be given to diagnose early psychiatric disorders.
PMCID: PMC1538574  PMID: 16831221
25.  Does Severity or Specific Joint Laxity Influence Clinical Outcomes of Anterior Cruciate Ligament Reconstruction? 
It generally is believed generalized joint laxity is one of the risk factors for failure of anterior cruciate ligament (ACL) reconstruction. However, no consensus exists regarding whether adverse effects on ACL reconstruction are attributable to joint-specific laxity or are related to the severity of generalized joint laxity. We therefore asked whether knee stability and functional outcomes would be related to joint-specific laxity and would differ according to the severity of generalized joint laxity. The Beighton and Horan criteria were used to assess joint laxity in 272 subjects. All elements are added to give an overall joint laxity score ranging from 0 to 5. Knee translation did not increase in proportion to the severity of the generalized joint laxity. Patients with scores less than 4 showed similar knee stability. When all variables, including the severity of generalized joint laxity, were considered, only hyperextension of the knee independently predicted knee stability and function. In patients with knee hyperextension, a bone-patellar tendon-bone autograft provided superior stability and function compared with a hamstring tendon autograft. Our data suggest knee hyperextension predicts postoperative stability and function regardless whether patients have severe generalized joint laxity.
Level of Evidence: Level III, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.
PMCID: PMC2835583  PMID: 19582525

Results 1-25 (801061)