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The text is the summary of recent articles on Freeman sheldon Syndrome at 75 thresold from National Library of Medicine (NLM). This information is subject to NCBI's Disclaimer and Copyright notice.
Patients with SHS present with contractures of the limbs and a distinctive triangular facies with prominent nasolabial folds . Calcaneovalgus deformity is frequent, as well as camptodactyly and ulnar deviation . MYH3 plays a pivotal role in Fetal Muscle development and mutations in this gene are associated with Freeman-Sheldon syndrome, distal arthrogryposis 8 (DA8), and Autosomal Dominant spondylocarpotarsal synostosis . We highlight the different features present in our patient and describe the etiology of the Freeman-Sheldon phenotype and how its clinical complications can be dealt with . By trio-whole exome sequencing, two undescribed de novo Mutations in NALCN were revealed .
General anesthesia with inhalational anesthetic and spontaneous respirations technique was used . With a predicted difficult airway, our team decided to provide a combined spinal-epidural anesthetic . Parental testing is thus essential for accurate risk assessment for future pregnancies and the use of new technologies with next generation sequencing (NGS) may improve the detection rate of mosaicism . Freeman-Sheldon syndrome (FSS) is a disease associated with missense Mutations in the motor domain of this myosin . It is the most severe form of distal arthrogryposis, leading to overcontraction of the hands, Feet, and orofacial muscles and other Joints of the body .
Our data suggest that the WT embryonic myosin motor is similar in contractile speed to the slow type I/β Cardiac based on the rate constant for ADP release and ADP affinity for actin-myosin . The majority of these patients have microstomia and Dental crowding, making Oral hygiene difficult and increasing the risk of caries . Clinical diagnosis requires microstomia, whistling-face appearance (pursed lips), H-shaped chin dimpling, nasolabial folds, and two or more contractures of Hands and Feet . We measured the contractile properties of Individual skeletal muscle cells and the activation and relaxation kinetics of isolated myofibrils from two adult individuals with an R672C substitution in embryonic myosin and distal arthrogryposis syndrome 2A (DA2A) or Freeman-Sheldon syndrome . We used molecular-inversion probes to screen for NALCN in a cohort of 202 distal arthrogryposis (DA)-affected individuals as well as concurrent exome sequencing of six other DA-affected individuals, thus revealing NALCN Mutations in ten additional families with "atypical" forms of DA .
In 2009, scientists successfully identified one missense mutation in MYH3 among 4 individuals with Freeman Sheldon syndrome (one autosomal dominant disease) through exome sequencing . Since then, exome sequencing has been widely used to identify disease causative or susceptibility genes in Mendelian disorders and complex diseases . We report a case of malignant hyperthermia in a 3-year-old girl with microstomia but no other features of Freeman-Sheldon syndrome . DA type 2A (DA2A or Freeman-Sheldon syndrome), caused by Mutations in MYH3, is typically considered the most severe of the DA syndromes . However, there is wide phenotypic variability among individuals with DA2A .
It is characterized by three basic abnormalities: microstomia with pouting Lips, camptodactyly with ulnar deviation of the fingers, and talipes equinovarus . Presence of microstomia is always associated with practical difficulties of Oral hygiene maintenance and increased susceptibility to caries . We tested the ability of an aggregate VEST gene score to identify candidate Mendelian disease genes, based on whole-exome sequencing of a small Number of disease cases . There are three basic abnormalities like microstomia with pouting Lips, camptodactyly with ulnar deviation of the Fingers and talipes equinovarus . Other associated less specific abnormalities are short broad Neck, kyphoscoliosis .
Here we are presenting a Newborn with Multiple congenital anomaly like microstomia with pouting Lips, H like dimple of the chin, hypoplastic alae nasi, plug like nostrils, short and broad Neck . Bilateral talipes equinovarus, gibbus, contracture of both upper and lower limbs with ulnar deviation of the Fingers of the Hand was noted . The patient was diagnosed as a case of Freeman Sheldon syndrome (whistling Face syndrome) on the basis of minimal diagnostic criteria, unique clinical and radiological features . Via exome-sequencing, genes harboring variants implicated in several Mendelian traits have already been identified . The underlying methodology in these studies is a multistep algorithm based on filtering variants identified in a small Number of affected individuals and depends on whether they are novel (not yet seen in public resources such as dbSNP), shared among affected individuals, and other external functional information on the variants .
A missense Mutation in MYH3 (a gene coding for the heavy chain of myosin), causing an F437I amino acid substitution, was identified that segregated with distal arthrogryposis in this family . This report describes a Chinese family with SHS over three generations in which all affected individuals showed vertical talus and one demonstrated preauricular tags on the Face . Two patients with clinical diagnosis of Freeman- Sheldon syndrome, confirmed by molecular study were described in this article . Additionally, clinical aspects, differential diagnosis and genetic basis of the disease were described as well as medical problems concerning patients with Freeman-Sheldon syndrome were discussed such as anesthetic aspects, Malignant hyperthermia and Pulmonary complications after surgery . Malignant hyperthermia and hyperpyrexia have been documented in FSS after General anesthesia related to the Neuropathy .
Microsomia is one of the main diagnostic criteria for Freeman-Sheldon syndrome, and it creates difficulty in working in the intraoral cavity . The above features are characteristic of Freeman-Sheldon syndrome also known as Whistling Face syndrome . Ultrasound scanning during 8(th) month of the Pregnancy showed the fetus to have facial abnormality and Bilateral clenched Hand and talipes with extension contractures of knees . These include eight HapMap individuals representing three populations, and four unrelated individuals with a rare dominantly inherited disorder, Freeman-Sheldon syndrome (FSS) . Using FSS as a proof-of-concept, we show that candidate genes for Mendelian disorders can be identified by exome sequencing of a small Number of unrelated, affected individuals .
Other common clinical features of SHS include prominent nasolabial folds, high arched palate, attached earlobes, mild cervical webbing, short stature, severe camptodactyly, ulnar deviation, and vertical talus and/or talipes equinovarus . Typically, the contractures are most severe at birth and non-progressive . SHS is inherited in an Autosomal dominant pattern but about half the cases are sporadic . Recently, Mutations in skeletal Muscle contractile genes MYH3 (myosin heavy chain 3), TNNT3 (troponin T3), and TPM2 (tropomyosin 2) were identified in patients with distal arthrogryposis DA2A (Freeman-Sheldon syndrome) or DA2B (Sheldon-Hall syndrome) . We asked whether the contractile genes responsible for distal arthrogryposis are also responsible for cases of familial clubfoot or vertical talus .
References: 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ,Press Refresh to fetch fresh content with references from pubmed. This content was cached on 2018-03-14 comments powered by Disqus
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