Congenital Contractural Arachnodactyly Research Articles

SS26 Surgical Management of Pediatric Renovascular Hypertension

Renovascular hypertension is the third most common cause of pediatric hypertension (HTN), and if left untreated, risks devastating cardiopulmonary complication, stroke, renal failure, and mortality. The impetus of this study was to identify risk factors responsible for persistent HTN necessitating reoperation. A retrospective analysis was performed of consecutive pediatric patients undergoing open surgical revascularization between 1981 and 2016. Anatomic phenotype and patient risk factors were analyzed using multinomial regression and Kaplan-Meier survival curves regarding perioperative outcomes including blood pressure control, morbidity, and secondary operations. There were 155 patients (70 girls, 85 boys), mean aged 9 years (6 months-19 years), who underwent an index operation, of whom 56 (36%) demonstrated left ventricular hypertrophy by echocardiogram. Thirty patients (19%) had neurofibromatosis, and 70 patients (45%) had abdominal aortic coarctations. Additional diagnoses identified included Williams syndrome, moyamoya disease, fibromuscular dysplasia, Beals syndrome, trisomy 21, Noonan syndrome, gonadal dysgenesis, Alagille syndrome, and Behçet disease. Malignant HTN and failure to thrive were commonly identified at the extremes of youth. Failed previous open or endovascular revascularizations affected 45 children (29%) prior to transfer to the authors' institution. There were 297 primary surgical interventions performed, including renal artery-aortic reimplantation (122), segmental renal artery-renal reimplantation (12), aortorenal bypass most commonly with hypogastric artery (49), segmental embolization (9), renal patch angioplasty (7), and partial or complete nephrectomy (21) in addition to concurrent visceral revascularization (20) and aortic revascularization by way of patch aortoplasty (28) and aortoaortic bypass (29). Surgical morbidity was minimal; renal insufficiency requiring dialysis did not occur. During follow-up that averaged 40 months, 29 children (19%) required reoperation, including both open surgical (22) and endovascular (5) procedures. Those children aged <5 years at the time of index surgery were statistically more likely to require reoperation (P < .05) in comparison to older children (Fig). Children undergoing remedial operations and those with midaortic syndrome were less likely to be cured of HTN. The overall experience revealed HTN to be cured in 67 children (43%), improved in 65 (42%), and unchanged in 21 (14%). There was no perioperative mortality. Contemporary surgical treatment of pediatric renovascular HTN requires an individualized approach providing sustainable benefit to nearly 90% of patients with negligible morbidity and no mortality. Extremes of youth increase the likelihood of reoperation. Patients undergoing remedial surgery and those with abdominal aortic coarctation are less likely to be cured of HTN. Judicious postoperative surveillance is imperative.

Exome Sequencing Identified a Novel FBN2 Mutation in a Chinese Family with Congenital Contractural Arachnodactyly.

Congenital contractural arachnodactyly (CCA) is an autosomal dominant disorder of connective tissue. CCA is characterized by arachnodactyly, camptodactyly, contrature of major joints, scoliosis, pectus deformities, and crumpled ears. The present study aimed to identify the genetic cause of a three-generation Chinese family with CCA. We successfully identified a novel missense mutation p.G1145D in the fibrillin-2 (FBN2) gene as the pathogenic mutation by whole exome sequencing (WES). The p.G1145D mutation occurs in the 12th calcium-binding epidermal growth factor-like (cbEGF) domain. The p.G1145D mutation caused a hydrophobic to hydrophilic substitution, altering the amino acid property from neutral to acidic. Three-dimensional structural analysis showed that this mutation could alter the conformation of the residue side chain, thereby producing steric clashes with spatially adjacent residues, disrupting the formation of H bonds and causing folding destabilization. Therefore, this amino acid appears to play an important role in the structure and function of FBN2. Our results may also provide new insights into the cause and diagnosis of CCA and may have implications for genetic counseling and clinical management.

Seizures as an Atypical Feature of Beal's Syndrome.

Congenital contractural arachnodactyly, commonly known as Beal's syndrome, is an extremely rare genetic disorder caused by mutations in the fibrillin-2 (FBN2) gene located on chromosome 5q23. It is an autosomal dominant inherited connective tissue disorder characterised by a Marfan-like body habitus, contractures, abnormally shaped ears and kyphoscoliosis. We report a seven-year-old Omani male who presented to the Sultan Qaboos University Hospital, Muscat, Oman, in 2014 with seizures. He was noted to have certain distinctive facial features and musculoskeletal manifestations; he was subsequently diagnosed with Beal's syndrome. Sequencing of the FBN2 gene revealed that the patient had a novel mutation which was also present in his mother; however, she had only a few facial features indicative of Beal's syndrome and no systemic involvement apart from a history of childhood seizures. To the best of the authors' knowledge, this is the first report of Beal's syndrome with seizure symptoms as a potential feature.

The clinical application of preimplantation genetic diagnosis for the patient affected by congenital contractural arachnodactyly and spinal and bulbar muscular atrophy.

To investigate the usefulness of preimplantation genetic diagnosis (PGD) for the patient affected by congenital contractural arachnodactyly (CCA) and spinal and bulbar muscular atrophy (SBMA). Multiple displacement amplification (MDA) was performed for whole genome amplification (WGA) of biopsied trophectoderm (TE) cells. Direct mutation detection by sequencing and next-generation sequencing (NGS)-based single nucleotide polymorphism (SNP) haplotyping were used for CCA diagnosis. Direct sequencing of the PCR products and sex determination by amplification of sex-determining region Y (SRY) gene were used for SBMA diagnosis. After PGD, the unaffected blastocyst (B4) was transferred in the following frozen embryo transfer (FET). In this PGD cycle, sixteen MII oocytes were inseminated by ICSI with testicular spermatozoa. Four blastocysts (B4, B5, B10, B13) were utilized for TE cell biopsy on day 5 after ICSI. After PGD, B4 was unaffected by CCA and SBMA. B5 was affected by CCA and carried SBMA. B10 was unaffected by CCA and carried SBMA. B13 was affected by CCA and unaffected by SBMA. B4 was the only unaffected blastocyst and transferred into the uterus for the subsequent FET cycle. The accuracy of PGD was confirmed by amniocentesis at 21weeks of gestation. A healthy boy weighing 2850g was born by cesarean section at the 38th week of gestation. PGD is a valid screening tool for patienst affected of CCA and SBMA to prevent transmission of these genetic diseases from parents to children.

Identification of a Novel Missense FBN2 Mutation in a Chinese Family with Congenital Contractural Arachnodactyly Using Exome Sequencing.

Congenital contractural arachnodactyly (CCA, OMIM 121050), also known as Beals-Hecht syndrome, is an autosomal dominant disorder of connective tissue. CCA is characterized by arachnodactyly, dolichostenomelia, pectus deformities, kyphoscoliosis, congenital contractures and a crumpled appearance of the helix of the ear. The aim of this study is to identify the genetic cause of a 4-generation Chinese family of Tujia ethnicity with congenital contractural arachnodactyly by exome sequencing. The clinical features of patients in this family are consistent with CCA. A novel missense mutation, c.3769T>C (p.C1257R), in the fibrillin 2 gene (FBN2) was identified responsible for the genetic cause of our family with CCA. The p.C1257R mutation occurs in the 19th calcium-binding epidermal growth factor-like (cbEGF) domain. The amino acid residue cysteine in this domain is conserved among different species. Our findings suggest that exome sequencing is a powerful tool to discover mutation(s) in CCA. Our results may also provide new insights into the cause and diagnosis of CCA, and may have implications for genetic counseling and clinical management.

Beals syndrome (congenital contractural arachnodactyly) in children: Clinical symptoms, diagnosis, treatment, and prevention

The paper deals with a rare monogenic connective tissue disease from a group of fibrillinopathies with autosomal dominant inheritance — Beals syndrome caused by a mutation in the FBN2 gene. Attention is drawn to the high phenotypic similarity of this disease and Marfan syndrome (FBN1 gene mutation), which is associated with the almost complete identity of two proteins: fibrillin 1 and fibrillin 2. The paper describes a clinical case of a child with Beals syndrome and the typical manifestations of the disease: asthenic constitution, arachnodactyly of the hands and feet, congenital contractures of the large and small joints, chest deformity, kyphoscoliosis, talpes, and crushed ears. The investigators made a differential diagnosis with other connective tissue diseases, such as Marfan syndrome, Stickler syndrome, Ehlers–Danlos syndrome, homocystenuria, and arthrogryposis. DNA diagnosis verified the Beals syndrome in the proband. Exon 28 in the FBN2 gene showed the previously undescribed missense mutation of c.3719G>A, resulting in the amino acid substitution of cysteine for tyrosine (p.Cys1240Tyr) in the structure of the protein fibrillin 2. A de novo mutation occurred. There is evidence for its pathogenicity in the development of the clinical symptoms of the disease. The problems of effective medical genetic counseling in this family are discussed.

Abstract 18260: Familial Beals- Hecht Syndrome Associated With Bicuspid Aortic Valve and Right Ventricular Apical Diverticulum. An Unusual Combination of Congenital Defects Diagnosed in Adulthood by Multimodality Imaging

Introduction: Congenital contractural arachnodactyly (CCA) is an autosomal dominant disorder. CCA is phenotypically similar to Marfan syndrome, typically not affecting the aorta or eyes. Right ventricle (RV) diverticulum with bicuspid aortic valve (BAV) and CCA is not described. Case: 48 year-old caucasian female: cardiac apical aneurysm, scoliosis, BAV, and diagnosis of CCA. CCA affected her mother, brother, and daughter. PE: 5’ 7", 128 pounds, scoliosis, arachnodactyly, wing span of 69”, Ghent Nosology score 5. Cardiac exam: unremarkable. CT chest: contrast: a 2.7 x 2.2 cm arterially enhancing thin-walled lobular structure at the cardiac apex communicating with RV. Echo: RV apical pouch: 2.2 x 1.7 cm, narrow neck - mild systolic expansion. RV size, function and strain: normal. BAV with trace AR. Ascending aorta: 3.5 cm. LVEF 73%. Cardiac MRI: 2 x 2 x 2.5 cm diverticulum arising from the RV apex, 5 mm neck communicating with the aneurysm and RV. No delayed enhancement of the myocardium/ RV diverticulum. Gene testing: 16 genes associated with familial thoracic aortic aneurysm and dissection tested. Patient: heterozygous for a novel D1532N variant in the FBN2 gene. This variant is not reported as a mutation or benign polymorphism. Discussion: CCA associated with BAV and RV diverticulum is not described. CCA is genetically linked to FBN2. Congenital ventricular diverticulum is a rare finding, very infrequently affecting the RV. Multimodality imaging and gene testing may lead to better identification of this malformation and its association with genetic diseases. There is no standardized treatment of RV diverticulum. This asymptomatic patient received conservative management.

Abnormal Activation of BMP Signaling Causes Myopathy in Fbn2 Null Mice.

Fibrillins are large extracellular macromolecules that polymerize to form the backbone structure of connective tissue microfibrils. Mutations in the gene for fibrillin-1 cause the Marfan syndrome, while mutations in the gene for fibrillin-2 cause Congenital Contractural Arachnodactyly. Both are autosomal dominant disorders, and both disorders affect musculoskeletal tissues. Here we show that Fbn2 null mice (on a 129/Sv background) are born with reduced muscle mass, abnormal muscle histology, and signs of activated BMP signaling in skeletal muscle. A delay in Myosin Heavy Chain 8, a perinatal myosin, was found in Fbn2 null forelimb muscle tissue, consistent with the notion that muscle defects underlie forelimb contractures in these mice. In addition, white fat accumulated in the forelimbs during the early postnatal period. Adult Fbn2 null mice are already known to demonstrate persistent muscle weakness. Here we measured elevated creatine kinase levels in adult Fbn2 null mice, indicating ongoing cycles of muscle injury. On a C57Bl/6 background, Fbn2 null mice showed severe defects in musculature, leading to neonatal death from respiratory failure. These new findings demonstrate that loss of fibrillin-2 results in phenotypes similar to those found in congenital muscular dystrophies and that FBN2 should be considered as a candidate gene for recessive congenital muscular dystrophy. Both in vivo and in vitro evidence associated muscle abnormalities and accumulation of white fat in Fbn2 null mice with abnormally activated BMP signaling. Genetic rescue of reduced muscle mass and accumulation of white fat in Fbn2 null mice was accomplished by deleting a single allele of Bmp7. In contrast to other reports that activated BMP signaling leads to muscle hypertrophy, our findings demonstrate the exquisite sensitivity of BMP signaling to the fibrillin-2 extracellular environment during early postnatal muscle development. New evidence presented here suggests that fibrillin-2 can sequester BMP complexes in a latent state.

A novel FBN2 mutation in a Chinese family with congenital contractural arachnodactyly

Congenital contractural arachnodactyly (CCA, OMIM: 121050) is an autosomal dominant condition that shares skeletal features with Marfan syndrome (MFS, OMIM: 154700), including contractures, arachnodactyly, dolichostenomelia, scoliosis, crumpled ears and pectus deformities but excluding the ocular and cardiovascular complications that characterize MFS. These two similar syndromes result from mutations in two genes belonging to the fibrillin family, FBN1 and FBN2, respectively. We successfully identified a novel FBN2 mutation (C1406R) in a Chinese family with CCA for over five generations. This mutation was detected in the patients of this family but not in the seven unaffected family members or 100 normal individuals. SIFT and PolyPhen analyses suggested that the mutation was pathogenic. We identified a missense mutation in the calcium binding-epidermal growth factor (cbEGF)-like domain. Our study extends the mutation spectrum of CCA and confirms a relationship between mutations in the FBN2 gene and the clinical findings of CCA.

Ghent Criteria an Aid to Diagnose Latent Systemic Diseases in Marfan Syndrome.

A 23-year-old tall female reported with a chief complaint of intermittent vague pain in the left lower posterior teeth region for the past two years. Her past medical history revealed that the patient has cardiac problem and visual impairment since birth and had not undergone any treatment for the same. Family history revealed that her parents and siblings are apparently healthy with no similar complaints. General examination revealed height measurement of 174.5 cms (upper segment-72.5 cms and lower segment -102 cm, long and slender extremities [Table/Fig-1] with spider- like fingers and toes (arachnodactyly) [Table/Fig-2], positive Walker’s sign [Table/Fig-3], Steinberg’s sign [Table/Fig-4] and pectus carinatum [Table/Fig-5]. Facial profile examination revealed dolicocephalic face, sunken eyes, incompetent lips, malar hypoplasia [Table/Fig-6]. Review of systems revealed impaired vision (myopia) [Table/Fig-1]: Thin and slender lower limb [Table/Fig-2]: Arachnodactyly [Table/Fig-3]: Walker’s sign (the distal phalange of the first and fifth fingers of the hand overlap when wrapped around the opposite wrist) [Table/Fig-4]: Steinberg’s sign (the thumb projects beyond the ulnar border while completely opposed within the clenched hand) [Table/Fig-5]: Pectus carinatum [Table/Fig-6]: Facial profile showing dolicocephalic face, incompetent lips, malar hypoplasia On intraoral examination patient had narrow upper and lower arch with crowding of teeth, high arched palate and multiple dental caries and root stumps [Table/Fig-7]. Correlating the history such as congenital cardiac anomaly, visual impairment and characteristic features such as dolicocephalic face, high arched palate, positive Walker’s and Steinberg’s sign the case was provisionally diagnosed as Marfan syndrome with a differential diagnosis of Ectopia Lentis syndrome, Ehlers-Danlos syndrome, Loeys-Dietz syndrome, Beals syndrome. [Table/Fig-7]: Showing crowding of teeth in upper arch and high arched palate Orthopantomogram (OPG) revealed root stumps 16,37,46 and coronal radiolucency in 36 involving pulp associated with diffuse periapical radiolucency suggestive of periapical abscess, coronal radiolucency in 26,27,47 involving pulp suggestive of dental caries, impacted 48, prominent antegonial notch bilaterally, malformed right condyle and flattening of left condyle [Table/Fig-8]. [Table/Fig-8]: OPG reveals alteration of condylar morphology in right and left TMJ, impaction, root stumps, dental caries On referral to cardiologist patient was subjected to Echocardiogram which revealed mild mitral valve prolapse with mitral regurgitation and mild tricuspid valve prolapse with tricuspid regurgitation, aortic dilatation with Z score=2. Ophthalmologist report revealed bilateral ectopia lentis and myopia (dioptre -4). Based on the revised Ghent criteria [1] in the absence of family history with aortic dilatation (Z=2), ectopia lentis and systemic score of 9 (wrist and thumb sign-3, pectus carinatum-2, scoliosis-1, facial features-1, myopia>3 diopter-1, mitral valve prolapse-1) the case was confirmed as Marfan syndrome. Patient was adviced extraction of root stumps 16,37 and 46 under antibiotic prophylaxis (Amoxicillin 2g one hour prior to extraction) and endodontic management of 26,27,36,47. On regular review visits for endodontic treatment, apprehensive and less sociable nature of the patient was evident. Many case reports of Marfan syndrome reported in the literature though was diagnosed based on Ghent criteria, the systemic score, aortic Z score, dioptre value has not been reported for all the cases [2–4]. In the present case the diagnosis of the common and other hidden systemic manifestations was arrived based on revised Ghent criteria and the aortic Z score of 2, dioptre value of -4 and systemic score of 9 were calculated. Unique features such as bilateral condylar malformation, prominent antegonial notch which were not reported in the other cases was observed in the present case.

Beals syndrome (congenital contractural arachnodactyly): prenatal ultrasound findings and molecular analysis

We report the prenatal findings in two cases of Beals syndrome. Both pregnancies presented with clinical features of arthrogryposis multiplex congenita/fetal akinesia syndrome (AMC/FAS), including clenched fists and multiple joint contractures on repeat prenatal ultrasound examinations. The first case was diagnosed as having Beals syndrome on physical examination shortly after birth and the diagnosis was confirmed by DNA analysis, shown as a point mutation in the fibrillin 2 (FBN2) gene. The second case was diagnosed with Beals syndrome following microarray analysis on amniocytes, which showed a deletion of the FBN2 gene. Although most cases with AMC/FAS carry a poor prognosis, Beals syndrome is consistent with normal cognitive development and a better prognosis. Thus, making the correct diagnosis is crucial, both pre- and postnatally, for accurate counseling and management.

Cirugía reparadora de la insuficiencia aórtica

IntroductionWe present our initial experience with isolated aortic valve repair or remodeling operation (Yacoub) in patients with aortic root dilatation. Short and mid-term follow-up data are reported. MethodsFrom 2009 to 2011, 25 patients underwent surgery. Yacoub remodeling surgery was carried out in 9 cases with root dilatation: anuloaortic ectasia in 8 cases, Beals Syndrome in one case. Coroneo® ring was implanted in 6 of these and subaortic Schäfers suture in 3. In the 16 cases isolated valve insufficency was the only pathology found (4 bicuspid cases). Echocardiogram was also carried out in the immediate postoperative period as well as one, six, 12 and 24 months after surgery. ResultsHospital mortality was 4% (1/25). Mean age was 44. Mean ischemic time was 54minutes for isolated valve repair and 139minutes for aortic root remodeling. Two patients were reoperated upon due to severe aortic regurgitation. Control echocardiograms showed satisfactory repair in 21 cases with minimum residual insufficiency and moderate regurgitation in 2 cases. ConclusionsOur technique of choice for aortic valve repair is the central plication being an intuitive and reproducible technique. In aortic regurgitation associated with aortic root dilatation the technique of choice is the Yacoub remodeling with Coroneo® ring, providing lasting annular support.

Unclassified cardiomyopathies in neuromuscular disorders

Unclassified cardiomyopathies (CMPs) include left ventricular hypertrabeculation or noncompaction (LVHT) and Takotsubo syndrome (TTS). Unclassified CMPs are frequently associated with noncardiac disease, including neuromuscular disorders (NMDs). This review aims at summarizing and discussing recent findings concerning the association of NMDs with unclassified CMPs. Literature search using the database PubMed from 1966 to June 2013 was performed. LVHT has been described in association with dystrophinopathies, myotonic dystrophies, zaspopathies, laminopathies, dystrobrevinopathies, oculopharyngeal muscular dystrophy, tropomyosin-1 mutations, multiminicore disease, Danon disease, mitochondrial disorders, myoadenylate deaminase deficiency, Pompe's disease, glycogen storage disease-IV, fatty acid oxidation disorder, Barth syndrome, ryanodine receptor mutation, inclusion body myopathy, dystrophic epidermolysis bullosa, Charcot-Marie-Tooth neuropathy, hereditary cobolamine deficiency, beta-thalassemia, poliomyelitis, and Friedreich ataxia. Takotsubo syndrome has been described in association with myasthenia gravis, amyotrophic lateral sclerosis, Guillain-Barre syndrome, rhabdomyolysis, mitochondrial disorder, hypokalemia-related myopathy, syndrome malin, hereditary sensorimotor neuropathy, Beals syndrome, polymyalgia rheumatica, and unclassified myopathy. It is important for treating physicians to know about these associations because treatment and outcome of LVHT, including artificial ventilation, are determined by the presence or absence of an NMD. There are also indications that LVHT in NMDs favors the development of TTS. LVHT and TTS may be associated with NMDs. The pathogenetic link between unclassified CMPs and NMDs remains elusive. Outcome of LVHT and treatment of TTS are additionally determined by the presence or absence of an NMD.

Immunolocalisation of fibrillin microfibrils in the calf metacarpal and vertebral growth plate

Overgrowth of limbs and spinal deformities are typical clinical manifestations of Marfan syndrome (MFS) and congenital contractural arachnodactyly (CCA), caused by mutations of the genes encoding fibrillin-1 (FBN1) and fibrillin-2 (FBN2), respectively. FBN1 mutations are also associated with acromicric (AD) and geleophysic dysplasias (GD), and with Weill-Marchesani syndrome (WMS), which is characterised by short stature. The mechanisms leading to such abnormal skeletal growth and the involvement of the fibrillins are not understood. Postnatal longitudinal bone growth mainly occurs in the epiphyseal growth plate. Here we investigated the organisation of fibrillin microfibrils in the growth plate of the long bone and vertebra immunohistochemically. Fibrillin-1 was dual-immunostained with elastin, with fibrillin-2 or with collagen X. We report that fibrillin microfibrils are distributed throughout all regions of the growth plate, and that fibrillin-1 and fibrillin-2 were differentially organised. Fibrillin-1 was more abundant in the extracellular matrix of the resting and proliferative zones of the growth plate than in the hypertrophic zone. More fibrillin-2 was found in the calcified region than in the other regions. No elastin fibres were observed in either the proliferative or hypertrophic zones. This study indicates that, as fibrillin microfibrils are involved in growth factor binding and may play a mechanical role, they could be directly involved in regulating bone growth. Hence, mutations of the fibrillins could affect their functional role in growth and lead to the growth disorders seen in patients with MFS, CCA, AD, GD and WMS.

Inguinal Swelling in a Child – Is it Always Hernia?

A 4-mo-old presented to emergency services with incessant crying. There was no history of fever or vomiting. Vital signs were within normal limits. On examination marfanoid habitus, micrognathia, clenched position of hands (fist-like), crumpled ears and multiple contractures of large joints were noted (Fig. 1a). Congenital contractural arachnodactyly (CCA) or Beal’s syndrome was suspected. Cardiac and ocular exam was normal. On abdominal exam there was no guarding, rigidity or abdominal distention, but a left tender and red, non-reducible, firm and oval inguinal swelling was noted (Fig. 1b). A working diagnosis of incarcerated inguinal hernia was made. However, bilateral non palpable testis led to suspicion of torsion of undescended testis. An ultrasound Doppler scan showed avascular left testis in inguinal canal. Emergency inguinal exploration was done and testicular torsion was confirmed. There was no return of blood supply on detorsion and left orchiectomy was performed (Fig. 1c). CCA is an autosomal dominantly inherited connective tissue disorder (CTD) caused by a mutation in FBN2 gene and is akin to Marfans syndrome [1]. Patients with CTD are prone to inguinal hernias [2]. Red and tender inguinal swelling in an infant with CTD can be a incarcerated inguinal hernia; however absence of abdominal signs like vomiting or distention should lead to suspicion of torsion of undescended testis specially in someone presenting with an empty scrotum. Other differential diagnosis include Amyand hernia (appendicitis in hernia), inguinal lymphadenitis, acute hydrocele or in rare instances cystic hygroma [3, 4].

Congenital contractural arachnodactyly (Beals-Hecht syndrome): a rare connective tissue disorder

Congenital contractural arachnodactyly (CCA) or Beals-Hecht syndrome (BHS) presents a very rare connective tissue disorder characterized by narrow body habitus, crumpled ears, arachnodactyly, contractures, and scoliosis. In our case report, the physical examination revealed typical physical findings to determine the physical diagnosis of BHS in contrast to negative finding on DNA analysis. From clinical point-of-view, it is important to include a complex clinical approach in making the diagnosis.

Musculo-Skeletal Abnormalities in Patients with Marfan Syndrome

BackgroundA leptosomic body type is tall and thin with long hands. Marfanoid features may be familial in nature or pathological, as occurs in congenital contractual arachnodactyly (Beal’s syndrome) and Shprintzen-Goldberg syndrome mimicking some of the changes of Marfan syndrome, although not accompanied by luxation of lens and dissecting aneurysm of aorta.MethodsIn this article we collected eight patients who were consistent with the diagnosis of Marfan syndrome via phenotypic and genotypic characterization.ResultsOur patients manifested a constellation of variable presentations of musculo-skeletal abnormalities ranging from developmental dysplasia of the hip, protrusio acetabuli, leg length inequality, patellar instability, scoliosis, to early onset osteoarthritis. Each abnormality has been treated accordingly.ConclusionThis is the first paper which includes the diagnosis and the management of the associated musculo-skeletal abnormalities in patients with Marfan syndrome, stressing that patients with Marfan syndrome are exhibiting great variability in the natural history and the severity of musculo-skeletal abnormalities.

Congenital Contractural Arachnodactyly; two unrelated newborns with novel clinical findings

Congenital Contractural Arachnodactyly (CCA; Beals syndrome) is a rare autosomal dominant disorder of connective tissue. CCA represents similar phenotypical features of Marfan syndrome such as tall stature and arachnodactyly, with contrasting multiple joint contractures involving elbows, knees and even fingers with typical crumpled ear helices. Here, we present two separate newborns representing novel findings such as retinal hemorrhage, bilateral simian lines and cryptorchism in addition to classical findings. However, pedigree analyses of patients were suggesting somatic mosaicism in addition to the represented distinct features of Beals syndrome; one with milder phenotype and even lack of typical crumpled ear helices, and the other with severe vertebral findings such as kyphoscoliosis.

Is losartan the drug for all seasons?

Francesco Ramirez is the Dr. Amy and James Elster Professor of Molecular Biology (Connective Tissue Diseases) in the Department of Pharmacology and Systems Therapeutics at the Mount Sinai School of Medicine in New York City. His long-standing research interest focuses on the role of ECM proteins in health and disease. Major accomplishments include the characterization of genetic lesions and pathophysiological mechanisms in osteogenesis imperfecta, Ehlers-Danlos syndrome, spondyloepiphyseal dysplasia, congenital contractural arachnodactyly and Marfan syndrome.

Aracnodactilia contractural congénita

Congenital contractural arachnodactyly (CCA) is a connective tissue disorder caused by an autosomal dominant mutation. Affected individuals show multiple involvement, including cardiac and, mainly, musculoskeletal abnormalities. Because of advances in pregnancy management and access to assisted reproduction techniques, situations such as that reported in the present article will become more frequent: we describe a dichorionic diamniotic twin gestation obtained by in vitro fertilization in a woman with CCA. The diagnostic challenges, therapeutic alternatives, maternal and neonatal outcomes, and the social and ethical repercussions of these cases are discussed.