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Frontiers in Endocrinology 2021Despite different genetic background, Noonan syndrome (NS) shares similar phenotype features to Turner syndrome (TS) such as short stature, webbed neck and congenital... (Comparative Study)
Comparative Study
BACKGROUND
Despite different genetic background, Noonan syndrome (NS) shares similar phenotype features to Turner syndrome (TS) such as short stature, webbed neck and congenital heart defects. TS is an entity with decreased growth hormone (GH) responsiveness. Whether this is found in NS is debated.
METHODS
Data were retrieved from combined intervention studies including 25 children diagnosed with NS, 40 diagnosed with TS, and 45 control children (all prepubertal). NS-children and TS-girls were rhGH treated after investigation of the GH/IGFI-axis. GH was measured with poly- and monoclonal antibodies; 24hGH-profile pattern analysed by PULSAR. The NS-children were randomly assigned to Norditropin 33 or 66 μg/kg/day, and TS-girls were consecutively treated with Genotropin 33 or 66 μg/kg/day.
RESULTS
Higher PULSAR-estimates of 24h-profiles were found in both NS-children and TS-girls compared to controls: Polyclonal GH24h-profile (Mean ± SD) was higher in both groups (44 ± 23mU/L, p<0.01 in NS; 51 ± 47, p<0.001 in TS; compared to 30 ± 23 mU/L in controls) as was GH-baseline (1.4 ± 0.6 mU/L in NS; 2.4 ± 2.4 mU/L in TS, p<0.01 for both, compared to 1.1 ± 1.2 mU/L in controls). Pre-treatment IGFI was 2.2 lower in NS-children (-1.7 ± 1.3) compared to TS-girls (0.6 ± 1.8, p<0.0001). GH, IGFI/IGFBP3-ratio, and chronological age at start of GH accounted for 59% of the variance in first-year growth response in NS.
CONCLUSION
Both prepubertal NS-children and TS-girls had a high GH secretion, but low IGFI/IGFBP3 levels only in NS-children. Both groups presented a broad individual response. NS-children showed higher response in IGFI and growth, pointing to higher responsiveness to GH treatment than TS-girls.
Topics: Body Height; Child; Female; Human Growth Hormone; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Male; Noonan Syndrome; Phenotype; Turner Syndrome
PubMed: 34858328
DOI: 10.3389/fendo.2021.737893 -
Traffic Injury Prevention 2021This study compared dummy kinematics and biomechanical responses with and without retractor pretensioning in a severe rear sled test. It compliments an earlier study...
OBJECTIVE
This study compared dummy kinematics and biomechanical responses with and without retractor pretensioning in a severe rear sled test. It compliments an earlier study with buckle pretensioning.
METHODS
Three rear tests were run at 40 km/h (25 mph) delta V with a lap-shoulder belted Hybrid III 50 male dummy on a 2013-18 Ford Escape driver seat and belt restraint. One test was with the lap-shoulder belts only, a second with retractor and anchor pretensioning and a third with only retractor pretensioning. The head, chest and pelvis were instrumented with triaxial accelerometers. The upper and lower neck, thoracic spine and lumbar spine had transducers measuring triaxial loads and moments. Lap belt load was measured. High-speed video recorded different views of the dummy motion. Dummy kinematics and biomechanical responses were compared to determine the influence of retractor belt pretensioning.
RESULTS
The dummy kinematics and biomechanical responses were essentially similar with and without retractor or retractor and anchor pretensioning in rear sled tests. There was an initial spike in lap belt load with pretensioning, but it did not result in different dummy head, neck or chest responses. In the tests, the dummy moved rearward away from the shoulder belt. The belts were tightened with the rapid pull on the webbing by pretensioning. The dummy loaded the seat, which yielded rearward restraining its motion. There was no significant effect of pretensioning on the dynamics of the dummy until late in rebound.
CONCLUSIONS
There were no significant differences in dynamics of the Hybrid III with and without retractor or retractor and anchor pretensioning in a 40 km/h (25 mph) rear sled test. Belt pretensioning did not influence biomechanical responses in the rear impact because the seat supported the dummy.
Topics: Acceleration; Accidents, Traffic; Biomechanical Phenomena; Computer Simulation; Head; Humans; Lumbar Vertebrae; Manikins; Neck; Snow; Stress, Mechanical; Thorax
PubMed: 33886404
DOI: 10.1080/15389588.2021.1910243 -
Journal of the American Association of... Oct 2021The spectrum of Turner syndrome (TS) includes Turner syndrome mosaicism (TSM), which is typically a nonhereditary chromosomal abnormality. Turner syndrome mosaicism...
The spectrum of Turner syndrome (TS) includes Turner syndrome mosaicism (TSM), which is typically a nonhereditary chromosomal abnormality. Turner syndrome mosaicism presents uncommonly to primary care providers (PCPs), who often fail to recognize the subtle signs. The average age at diagnosis for common TS and TSM karyotype is 5.4 years, averaging 7.3 years. Often genetic confirmation, management, and recommended surveillance are delayed. Oftentimes, the PCP suspects a genetic etiology of an unusual phenotype, such as pinna placement or other unusual ear configurations, webbed neck with low posterior hairline, wide-spaced nipples, or short stature among other presentations. The PCP or geneticist orders diagnostic studies to confirm the diagnosis, such as a karyotype. After diagnosis, the PCP refers to the geneticist who initiates surveillance and makes recommendations for management. There are potential neurocognitive, cardiovascular, renal, reproductive, and endocrine issues. Treatment literature is vague and parental concerns are linked to quality mental health and quality of life for the family member with TS or TSM. The purpose of this article was to use a case study to introduce the topic of TS and TSM and to assist the PCP in the identification and management of patient and family concerns.
Topics: Humans; Karyotyping; Mosaicism; Primary Health Care; Quality of Life; Turner Syndrome
PubMed: 34628444
DOI: 10.1097/JXX.0000000000000643 -
Zhonghua Er Ke Za Zhi = Chinese Journal... Sep 2021To explore the clinical characteristics and mutation spectrum of ALPK3-related pediatric cardiomyopathy and craniofacial-skeletal abnormalities in children. The... (Review)
Review
To explore the clinical characteristics and mutation spectrum of ALPK3-related pediatric cardiomyopathy and craniofacial-skeletal abnormalities in children. The clinical data during a follow-up of 11 years including clinical features, echocardiogram, electrocardiogram, cardiac magnetic resonance, genetic testing, and other data of a child firstly diagnosed with ALPK3 gene-related cardiomyopathy and craniofacial-skeletal abnormalities in China were collected retrospectively. The literatures containing the keyword of "ALPK3 gene" published in the China National Knowledge Infrastructure, Wanfang database and PubMed were collected up to November 2020. Then, the clinical features and gene mutations of ALPK3 gene-related pediatric cardiomyopathy with craniofacial-skeletal features were summarized. A female patient aged 10 months who presented with an enlarged heart for 2 months, was admitted to the hospital and initially diagnosed with endocardial elastic fibrosis. The echocardiography showed features of dilated left ventricle (LV) and LV systolic dysfunction. Low-set ears, webbed neck, a grade 2/6 systolic murmur at lower left sternal area and bilateral absent flexion creases of dig were observed. After treatment, the size and function of the heart recovered to normal at age 13 months. However, the ventricular septum and LV wall were thicker than normal values. Then, the diagnosis was revised to hypertrophic cardiomyopathy(HCM) and suspected congenital malformation syndrome. LV hypertrophy (LVH) progressed slowly before the age of 8 years and then progressed rapidly. At age 9 years, compound heterozygous ALPK3 mutations (c.721dup, p.Y241Lfs*42(exon 1) and c.4840C>T, p.R1614*(exon 10)) were detected in the proband and the mutations had not been reported previously. Then, the final diagnosis of ALPK3 gene-related pediatric cardiomyopathy with craniofacial-skeletal features was made. During the follow up of 11 years, regular follow-up echocardiographic images showed progressive LVH. At age 11 years, electrocardiogram showed LVH, ST-T changes in multiple-lead, T wave inversion, and prolonged QT intervals. Cardiac magnetic resonance showed biventricular hypertrophy and late gadolinium enhancement showed non-uniform enhancement of left and right ventricular myocardium. A total of 7 articles published in English were retrieved, and no Chinese literature was found. Twenty-eight cases were reported in the articles plus the patient in this study. Twenty-four mutations were reported worldwide, 18 patients carried homozygous mutations and 10 patients compound heterozygous mutations. Eleven patients showed dilated cardiomyopathy (DCM) at early stage of disease, and 10 of them transitioned to HCM at the disease progression stage. Eight patients presented with HCM at early stage of disease. Nine patients initially exhibited a mixed phenotype of DCM and HCM, and 6 of them eventually progressed to HCM. Electrocardiogram showed prolonged QT interval. Extracardiac features included short stature, special face, cleft palate, webbed neck, joint contracture, and scoliosis, etc. Progressive myocardial hypertrophy is a major feature of ALPK3 gene-related cardiomyopathy with craniofacial-skeletal malformations. Precise diagnosis depends on molecular genetic techniques. More cases should be accumulated for further analysis on the genotype-phenotype correlation and prognosis assessment.
Topics: Cardiomyopathies; Cardiomyopathy, Hypertrophic; Child; Contrast Media; Female; Gadolinium; Humans; Infant; Retrospective Studies
PubMed: 34645221
DOI: 10.3760/cma.j.cn112140-20210222-00150 -
Archives of Endocrinology and Metabolism Nov 2021To investigate the presence of chromosome mosaicism, especially for the presence of Y derived material in 45,X women with Turner syndrome (TS).
OBJECTIVE
To investigate the presence of chromosome mosaicism, especially for the presence of Y derived material in 45,X women with Turner syndrome (TS).
METHODS
FISH and PCR were performed for the presence of chromosome mosaicism and Y-derived-material and genetic findings were correlated to clinical data.
RESULTS
Thirty-one participants were enrolled: 18 (58%) had chromosome mosaicisms (FISH), Y-derived material was found in 2. Yet, SRY primer was found with PCR in only one of them and DYZ3 was not found. The most frequent clinical findings were short or webbed neck (81,82%), high-arched palate (78%), breast hypertelorism, e cubitus valgus and genu valgus (57.6%, both), short fourth metacarpals (46.9%), epicanthic folds (43.8%), shield chest (43.8%), lymphedema (37.5%), and low set ears (34.4%). Both patients with Y-derived-material had primary amenorrhea, dyslipidemia and reached the height of 150 cm despite not treated with recombinant growth hormone (GHr). One of them showed 26% of leukocytes with Y-derived material and few clinical findings.
CONCLUSION
FISH techniques proved efficient in detecting chromosome mosaicisms and Y-derived material and searching in different tissues such as mouth cells is critical due to the possibility of tissue-specific mosaicism. Phenotypical variance in TS may be a signal of chromosome mosaicisms, especially with the presence of Y-derived material.
Topics: Body Height; Chromosomes; Female; Humans; Mosaicism; Polymerase Chain Reaction; Turner Syndrome
PubMed: 34762780
DOI: 10.20945/2359-3997000000403 -
GMS Interdisciplinary Plastic and... 2017The webbed neck deformity or pterygium colli is the number one symptom of the Turner syndrome that leads the patient to consult a doctor. Various but rare surgical...
The webbed neck deformity or pterygium colli is the number one symptom of the Turner syndrome that leads the patient to consult a doctor. Various but rare surgical approaches have been described to correct this deformity. We reviewed our experience with the surgical correction of the pterygium colli. Through five clinical cases, we describe the surgical technique with a lateral approach which provides a better control of the operative site, allows for the excision of the underlying trapezial fascial web, thus preventing recurrence seen in the posterior approach, and restores a normal hairline. No postoperative wound infection occurred. No recurrence was observed through 24 months. Three patients developed hypertrophic scars. The lateral approach associated with an advanced flap and a Z-plasty is an effective technique for correction of this neck deformity. The presence of a multidisciplinary team, formed with maxillofacial and plastic surgeons, endocrinologists and psychologists, is required to treat these patients allowing reintegration into society and family.
PubMed: 28275532
DOI: 10.3205/iprs000106 -
European Journal of Pediatrics Mar 2024Mendelian disorders of the epigenetic machinery (MDEMs) are caused by genetic mutations, a considerable fraction of which are associated with epigenetic modification....
Mendelian disorders of the epigenetic machinery (MDEMs) are caused by genetic mutations, a considerable fraction of which are associated with epigenetic modification. These MDEMs exhibit phenotypic overlap broadly characterized by multiorgan abnormalities. The variant detected in genes associated with epigenetic modification can lead to short stature accompanied with multiple system abnormalities. This study is aimed at presenting and summarizing the diagnostic rate, clinical, and genetic profile of MDEMs-associated short stature. Two hundred and fourteen short-stature patients with multiorgan abnormalities were enrolled. Clinical information and whole exome sequence (WES) were analyzed for these patients. WES identified 33 pathogenic/likely pathogenic variants in 19 epigenetic modulation genes (KMT2A, KMT2D, KDM6A, SETD5, KDM5C, HUWE1, UBE2A, NIPBL, SMC1A, RAD21, CREBBP, CUL4B, BPTF, ANKRD11, CHD7, SRCAP, CTCF, MECP2, UBE3A) in 33 patients (15.4%). Of note, 19 variants had never been reported previously. Furthermore, these 33 variants were associated with 16 different disorders with overlapping clinical features characterized by development delay/intelligence disability (31/33; 93.9%), small hands (14/33; 42.4%), clinodactyly of the 5th finger (14/33; 42.4%), long eyelashes (13/33; 39.4%), and hearing impairment (9/33; 27.3%). Additionally, several associated phenotypes are reported for the first time: clubbing with KMT2A variant, webbed neck with SETD5 variant, retinal detachment with CREBBP variant, sparse lateral eyebrow with HUWE1 variant, and long palpebral fissure with eversion of the lateral third of the low eyelid with SRCAP variant.Conclusions: Our study provided a new conceptual framework for further understanding short stature. Specific clinical findings may indicate that a short-stature patient may have an epigenetic modified gene variant.
Topics: Humans; Mutation; Abnormalities, Multiple; Genotype; Phenotype; Epigenesis, Genetic; Ubiquitin-Conjugating Enzymes; Cell Cycle Proteins; Tumor Suppressor Proteins; Ubiquitin-Protein Ligases; Cullin Proteins; Methyltransferases
PubMed: 38170291
DOI: 10.1007/s00431-023-05385-3 -
Indian Journal of Otolaryngology and... Jun 2023Turner syndrome is the most common chromosomal anomaly in females. The typical features include short stature, amenorrhoea, short webbed neck, shielded chest and many...
Turner syndrome is the most common chromosomal anomaly in females. The typical features include short stature, amenorrhoea, short webbed neck, shielded chest and many comorbidities like osteoporosis, cardiac anomalies, diabetes and hypothyroidism. Primary hyperparathyroidism caused by parathyroid adenoma is rarely reported in patients of turner syndrome. The exact cause is not known at present. We report a case of a 21 years old patient of Turner syndrome who had symptoms of renal stones and hypercalcemia. USG neck and sestamibi scans revealed left inferior parathyroid adenoma. Surgical excision of the involved gland was done which led to normalization of S. calcium and PTH levels. Although hyperparathyroidism is extremely rare in patients of Turner syndrome, any symptoms of renal stones, pathological fractures and hypercalcemia should raise the suspicion of parathyroid adenoma. Surgical management should be planned as early as possible.
PubMed: 37274961
DOI: 10.1007/s12070-022-03322-8 -
Annales D'endocrinologie Feb 2019To investigate the karyotype, clinical manifestations and natural and therapeutic outcome of Turner syndrome (TS) in China.
OBJECTIVE
To investigate the karyotype, clinical manifestations and natural and therapeutic outcome of Turner syndrome (TS) in China.
METHOD
A total of 124 TS patients with definite diagnosis were included. Karyotype, main clinical signs, sexual development and therapeutic outcome were analyzed.
RESULTS
TS karyotype was classified in 4 types: monosomy (32.7%), mosaic (15.9%), variant (23.9%) and mosaic with variant (27.4%). All patients showed short stature, with mean adult height<145cm. Sixteen percent of adolescent patients showed spontaneous breast development and 8% spontaneous menstruation. The rate of spontaneous sexual development was lowest in the monosomy karyotype. Common signs included cubitus valgus and wide breast space in about 50% of patients, epicanthus and skin nevus in 30% and webbed neck and shield chest in 10-20%. More than 10% of patients had associated heart, kidney or thyroid abnormalities. The rate of kidney malformation was highest in the monosomy karyotype. Growth hormone (GH) therapy can accelerate growth, with 7.6cm and 6.7cm increase in height in the first and second years of therapy respectively, slowing to 5.7cm and 4.1cm in the third and fourth years. Treated patients who reached nearly adult height were 10.2cm taller than untreated patients. Therapeutic effect correlated with GH therapy duration.
CONCLUSION
TS patients showed a variety of karyotypes, related to the diversity of clinical manifestations and outcomes. Sexual development and adult height were poorer in monosomy karyotypes than in other types.
Topics: Adolescent; Body Height; Breast; Child; Child, Preschool; China; Female; Genetic Variation; Heart Defects, Congenital; Human Growth Hormone; Humans; Infant; Karyotype; Karyotyping; Kidney; Menstruation; Monosomy; Mosaicism; Puberty; Sexual Development; Thyroid Diseases; Treatment Outcome; Turner Syndrome
PubMed: 29580553
DOI: 10.1016/j.ando.2017.10.011 -
Saudi Journal of Anaesthesia 2016Multiple pterygium syndrome (MPS) is a very rare autosomal recessive disorder characterized by flexion of joint and digit contractures, skin webbing, cleft palate,...
Multiple pterygium syndrome (MPS) is a very rare autosomal recessive disorder characterized by flexion of joint and digit contractures, skin webbing, cleft palate, deformity of the spine, and cervical spine fusion. Difficult airway is associated mainly due to micrognathia, retrognathia, webbing of the neck, and limitation of the mouth opening and neck extension. We are reporting a case of a 5-year-old female diagnosed with MPS and exhibiting a bilateral club foot and congenital vertical talus. The patient was posted for manipulation and above the knee casting under general anesthesia.
PubMed: 27375397
DOI: 10.4103/1658-354X.174901