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Journal of Cardiovascular Development... Oct 2021Turner syndrome is a rare disorder resulting from complete or partial loss of the second sex chromosome. Common manifestations include delayed growth, premature ovarian... (Review)
Review
Turner syndrome is a rare disorder resulting from complete or partial loss of the second sex chromosome. Common manifestations include delayed growth, premature ovarian failure, congenital heart defects, endocrine disorders, lymphedema, and webbed neck. People with Turner syndrome have significantly increased mortality risk primarily due to cardiovascular abnormalities. The mechanisms that lead to these defects are not completely understood and are obscured by the significant variability of both karyotype and phenotype without consistent correlation between the two. This paper presents a review of the recent literature surrounding the symptoms, mechanisms, diagnosis, and treatment of Turner syndrome with a focus on cardiovascular manifestations. With technological advancements in genetics, the molecular processes of Turner syndrome have begun to be dissected. Certain genes on the X chromosome that typically escape inactivation have been implicated in both specific manifestations and broader risk categories. Recently identified genome-wide epigenetic changes may help explain the variability in presentation. It remains unclear as to how the combination of these factors results in the overall clinical picture, but advances in genomic, genetic, epigenetic, and -omics technology hold promise for providing insights that will improve the medical management of individuals with Turner syndrome.
PubMed: 34821691
DOI: 10.3390/jcdd8110138 -
American Family Physician Aug 2007Turner syndrome occurs in one out of every 2,500 to 3,000 live female births. The syndrome is characterized by the partial or complete absence of one X chromosome (45,X... (Review)
Review
Turner syndrome occurs in one out of every 2,500 to 3,000 live female births. The syndrome is characterized by the partial or complete absence of one X chromosome (45,X karyotype). Patients with Turner syndrome are at risk of congenital heart defects (e.g., coarctation of aorta, bicuspid aortic valve) and may have progressive aortic root dilatation or dissection. These patients also are at risk of congenital lymphedema, renal malformation, sensorineural hearing loss, osteoporosis, obesity, diabetes, and atherogenic lipid profile. Patients usually have normal intelligence but may have problems with nonverbal, social, and psychomotor skills. Physical manifestations may be subtle but can include misshapen ears, a webbed neck, a broad chest with widely spaced nipples, and cubitus valgus. A Turner syndrome diagnosis should be considered in girls with short stature or primary amenorrhea. Patients are treated for short stature in early childhood with growth hormone therapy, and supplemental estrogen is initiated by adolescence for pubertal development and prevention of osteoporosis. Almost all women with Turner syndrome are infertile, although some conceive with assisted reproduction.
Topics: Bone Density Conservation Agents; Craniofacial Abnormalities; Female; Heart Defects, Congenital; Hormone Replacement Therapy; Human Growth Hormone; Humans; Infertility, Female; Karyotyping; Osteoporosis; Turner Syndrome
PubMed: 17708142
DOI: No ID Found -
American Family Physician Jan 2014Noonan syndrome is a common genetic disorder that causes multiple congenital abnormalities and a large number of potential health conditions. Most affected individuals...
Noonan syndrome is a common genetic disorder that causes multiple congenital abnormalities and a large number of potential health conditions. Most affected individuals have characteristic facial features that evolve with age; a broad, webbed neck; increased bleeding tendency; and a high incidence of congenital heart disease, failure to thrive, short stature, feeding difficulties, sternal deformity, renal malformation, pubertal delay, cryptorchidism, developmental or behavioral problems, vision problems, hearing loss, and lymphedema. Familial recurrence is consistent with an autosomal dominant mode of inheritance, but most cases are due to de novo mutations. Diagnosis can be made on the basis of clinical features, but may be missed in mildly affected patients. Molecular genetic testing can confirm diagnosis in 70% of cases and has important implications for genetic counseling and management. Most patients with Noonan syndrome are intellectually normal as adults, but some may require multidisciplinary evaluation and regular follow-up care. Age-based Noonan syndrome-specific growth charts and treatment guidelines are available.
Topics: Adolescent; Adult; Age Distribution; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Noonan Syndrome; Young Adult
PubMed: 24444506
DOI: No ID Found -
Cold Spring Harbor Molecular Case... Apr 2019Advancing the clinical utility of whole-exome sequencing (WES) for patients with suspected genetic disorders is largely driven by bioinformatics approaches that...
Advancing the clinical utility of whole-exome sequencing (WES) for patients with suspected genetic disorders is largely driven by bioinformatics approaches that streamline data processing and analysis. Herein, we describe our experience with implementing a semiautomated and phenotype-driven WES diagnostic workflow, incorporating both the DRAGEN pipeline and the Exomiser variant prioritization tool, at an academic children's hospital with an ethnically diverse pediatric patient population. We achieved a 41% molecular diagnostic rate for 66 duo-, quad-, or trio-WES cases, and 28% for 40 singleton-WES cases. Preliminary results were returned to ordering physicians within 1 wk for 12 of 38 (32%) probands with positive findings, which were instrumental in guiding the appropriate clinical management for a variety of patients, especially in critical care settings. The semiautomated and streamlined WES workflow also enabled us to identify novel variants in candidate disease genes in patients with developmental delay and autism and immune disorders and cancer, including , , , , , and Together, we demonstrated the implementation of a streamlined WES workflow that was successfully applied for both clinical and research purposes.
Topics: Adolescent; Autism Spectrum Disorder; Child; Child, Preschool; Early Diagnosis; Female; Genetic Predisposition to Disease; Humans; Immune System Diseases; Infant; Infant, Newborn; Male; Neoplasms; Sensitivity and Specificity; Time Factors; Exome Sequencing; Workflow; Young Adult
PubMed: 30755392
DOI: 10.1101/mcs.a003756 -
Orphanet Journal of Rare Diseases Jan 2007Noonan Syndrome (NS) is characterised by short stature, typical facial dysmorphology and congenital heart defects. The incidence of NS is estimated to be between 1:1000... (Review)
Review
Noonan Syndrome (NS) is characterised by short stature, typical facial dysmorphology and congenital heart defects. The incidence of NS is estimated to be between 1:1000 and 1:2500 live births. The main facial features of NS are hypertelorism with down-slanting palpebral fissures, ptosis and low-set posteriorly rotated ears with a thickened helix. The cardiovascular defects most commonly associated with this condition are pulmonary stenosis and hypertrophic cardiomyopathy. Other associated features are webbed neck, chest deformity, mild intellectual deficit, cryptorchidism, poor feeding in infancy, bleeding tendency and lymphatic dysplasias. The syndrome is transmitted as an autosomal dominant trait. In approximately 50% of cases, the disease is caused by missense mutations in the PTPN11 gene on chromosome 12, resulting in a gain of function of the non-receptor protein tyrosine phosphatase SHP-2 protein. Recently, mutations in the KRAS gene have been identified in a small proportion of patients with NS. A DNA test for mutation analysis can be carried out on blood, chorionic villi and amniotic fluid samples. NS should be considered in all foetuses with polyhydramnion, pleural effusions, oedema and increased nuchal fluid with a normal karyotype. With special care and counselling, the majority of children with NS will grow up and function normally in the adult world. Management should address feeding problems in early childhood, evaluation of cardiac function and assessment of growth and motor development. Physiotherapy and/or speech therapy should be offered if indicated. A complete eye examination and hearing evaluation should be performed during the first few years of schooling. Preoperative coagulation studies are indicated. Signs and symptoms lessen with age and most adults with NS do not require special medical care.
Topics: Adolescent; Adult; Child; Child Development; Child, Preschool; Female; Genetic Counseling; Humans; Infant; Infant, Newborn; Intracellular Signaling Peptides and Proteins; Mutation, Missense; Noonan Syndrome; Pregnancy; Prenatal Diagnosis; Prognosis; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Protein Tyrosine Phosphatases
PubMed: 17222357
DOI: 10.1186/1750-1172-2-4 -
Orphanet Journal of Rare Diseases Dec 2006KBG syndrome is a rare condition characterised by a typical facial dysmorphism, macrodontia of the upper central incisors, skeletal (mainly costovertebral) anomalies and... (Review)
Review
KBG syndrome is a rare condition characterised by a typical facial dysmorphism, macrodontia of the upper central incisors, skeletal (mainly costovertebral) anomalies and developmental delay. To date, KBG syndrome has been reported in 45 patients. Clinical features observed in more than half of patients that may support the diagnosis are short stature, electroencephalogram (EEG) anomalies (with or without seizures) and abnormal hair implantation. Cutaneous syndactyly, webbed short neck, cryptorchidism, hearing loss, palatal defects, strabismus and congenital heart defects are less common findings. Autosomal dominant transmission has been observed in some families, and it is predominantly the mother, often showing a milder clinical picture, that transmits the disease. The diagnosis is currently based solely on clinical findings as the aetiology is unknown. The final diagnosis is generally achieved after the eruption of upper permanent central incisors at 7-8 years of age when the management of possible congenital anomalies should have been already planned. A full developmental assessment should be done at diagnosis and, if delays are noted, an infant stimulation program should be initiated. Subsequent management and follow-up should include an EEG, complete orthodontic evaluation, skeletal investigation with particular regard to spine curvatures and limb asymmetry, hearing testing and ophthalmologic assessment.
Topics: Abnormalities, Multiple; Adolescent; Adult; Bone and Bones; Child; Child, Preschool; Developmental Disabilities; Face; Female; Growth Disorders; Humans; Incisor; Infant; Infant, Newborn; Male; Nervous System Diseases; Rare Diseases; Sensation Disorders; Syndrome; Young Adult
PubMed: 17163996
DOI: 10.1186/1750-1172-1-50 -
Journal of the American Academy of... Apr 2020Sprengel deformity is the main congenital shoulder deformity seen in children. First described by Otto Sprengel in 1891, it consists of a high-riding, dysplastic, and...
UNLABELLED
Sprengel deformity is the main congenital shoulder deformity seen in children. First described by Otto Sprengel in 1891, it consists of a high-riding, dysplastic, and malrotated scapula leading to functional and cosmetic impairments. It has never been reported in siblings.
CASE PRESENTATION
Two sisters, 8 and 9 years old, presented for an evaluation of atraumatic limitation in the shoulder range of motion and neck webbing with an unknown family history. Physical examination revealed a small high-riding scapula, webbed neck, and painless limitation in shoulder abduction (<70°) and flexion (<80°). The 9-year-old sibling had a bilateral shoulder involvement, and the younger had unilateral. Imaging revealed bony and fibrous omovertebral connections between the dysplastic scapulas and cervical spine along with Klippel-Feil deformities. Both sisters underwent scapula repositioning via a modified Woodward procedure. The omovertebral connection was resected followed by scapula derotation and inferior migration. Both had a dramatic improvement in cosmesis and near-complete restoration of shoulder function at follow-up.
CONCLUSIONS
Although uncommon, Sprengel deformity results in notable derangement of shoulder function. If untreated, children experience difficulty with most overhead activities and often have cosmetic reports. Although no previous genetic link has been identified, its presence in biological sisters suggests that more research is needed.
Topics: Cervical Vertebrae; Child; Congenital Abnormalities; Female; Humans; Scapula; Shoulder Joint; Siblings
PubMed: 32377613
DOI: 10.5435/JAAOSGlobal-D-19-00120