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Molecular Genetics & Genomic Medicine Apr 2020Noonan Syndrome is a developmental disorder characterized by a distinctive phenotype including facial dysmorphism, webbed neck, short stature, heart defects, and...
BACKGROUND
Noonan Syndrome is a developmental disorder characterized by a distinctive phenotype including facial dysmorphism, webbed neck, short stature, heart defects, and variable cognitive deficits as major features. Over the years, neuropsychological and behavioral studies explored alteration of cognitive functioning and related domains, such as learning, memory, and attention. To our knowledge, however, data concerning the language profile in this disorder is scarce. The aim of the present study was to detect specific language functioning combining nonverbal intelligence quotient and language abilities and to pinpoint strengths and weaknesses in the language domains.
METHODS
The language profile of 37 Italian participants with molecularly confirmed diagnosis of Noonan Syndrome was evaluated using specific tools to assess vocabulary and grammar comprehension and production, as well as phonological development.
RESULTS
We observed that 78% of affected individuals exhibited language impairment. Within language domains, the strong area was lexical production and grammar production was the weak area. Almost half the participants manifested a similar trend of specific language impairment. Nonverbal intelligence quotient only correlated with grammar comprehension.
CONCLUSION
Our study expands present knowledge about the language profile in NS, and provides data that could enable more effective patient management and appropriate intervention.
Topics: Adolescent; Child; Child, Preschool; Comprehension; Female; Humans; Intelligence Tests; Language Development Disorders; Language Tests; Male; Noonan Syndrome; Protein Tyrosine Phosphatase, Non-Receptor Type 11
PubMed: 32059087
DOI: 10.1002/mgg3.1069 -
International Journal of Environmental... Oct 2019Physical manifestations of Turner syndrome include short stature, a webbed neck, and a shield chest with widely spaced nipples. An aspect of the disease which has not...
Physical manifestations of Turner syndrome include short stature, a webbed neck, and a shield chest with widely spaced nipples. An aspect of the disease which has not been sufficiently explored so far is the tactile sensitivity of Turner syndrome patients. Thus, the aim of the study was to assess the threshold of tactile sensitivity on hands and feet of women suffering from Turner syndrome. Information on the participants of the study was collected on the basis of questionnaires, as well as anthropometric measurements using a skinfold caliper. Semmes-Weinstein Aesthesiometer was used to find the tactile sensitivity threshold of hands and feet of study participants. Based on the results of the study, significant differences in tactile sensitivity between women with Turner syndrome and healthy women were found. Affected women seem be more sensitive to the touch on the feet than healthy volunteers. The results of the study showed that the tactile sensitivity of women with Turner syndrome is different from that of healthy women.
Topics: Adolescent; Adult; Child; Female; Humans; Middle Aged; Touch; Touch Perception; Turner Syndrome; Young Adult
PubMed: 31614840
DOI: 10.3390/ijerph16203870 -
Cureus May 2023Webbed neck deformity is a congenital anomaly that exists in several syndromes. Various techniques for surgically correcting the webbed neck deformity have been...
Webbed neck deformity is a congenital anomaly that exists in several syndromes. Various techniques for surgically correcting the webbed neck deformity have been described in the literature, each comes with its own advantages and disadvantages. The aim of surgery is to achieve normal neck contour and symmetrical hairline, avoid excessive scarring over the anterior and lateral neck, and limit recurrence. In this report, we described our experience in managing a case of Turner syndrome with bilateral webbed neck deformity using the modified five-flap Z-plasty technique.
PubMed: 37346202
DOI: 10.7759/cureus.39312 -
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 -
Journal of Otolaryngology - Head & Neck... Sep 2022Lateral canthal webbing is a known complication of blepharoplasty, which occurs when the lateral aspect of the upper blepharoplasty incision is taken below the equator...
BACKGROUND
Lateral canthal webbing is a known complication of blepharoplasty, which occurs when the lateral aspect of the upper blepharoplasty incision is taken below the equator of the lateral canthus. Removing excessive eyelid skin laterally can also result in a lateral canthal web. Currently, there is no standard approach for addressing this complication.
METHODS
Retrospective review of single surgeon practice between 2011 and 2019. All patients underwent revision surgery using the proposed single Z-plasty technique.
RESULTS
Twenty-three patients referred for lateral canthal web were included in the study. All patients had previous upper lid blepharoplasty, with the initial procedure occurring 8-63 months prior to the referral for revision. The majority of the blepharoplasties occurred in Ontario (n = 19), but some patients also underwent surgery in Alberta (n = 1), British Columbia (n = 1), and United States (n = 1). The initial surgeries were performed by a variety of specialities including plastic surgery (n = 16), otolaryngology (n = 4), ophthalmology (n = 2), and family medicine (n = 1). Following revision surgery using the single Z-plasty technique, all patients reported a subjective increase in functional and aesthetic satisfaction. No further revision surgery was required for any of these patients.
CONCLUSION
The single Z-plasty technique is simple, robust, and could be easily incorporated into any cosmetic practice to address this complication of blepharoplasty.
Topics: Blepharoplasty; Eyelids; Humans; Lacrimal Apparatus; Plastic Surgery Procedures; Reoperation
PubMed: 36114564
DOI: 10.1186/s40463-022-00585-7 -
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 -
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