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American Journal of Medical Genetics.... Feb 2023Phenotype analysis of the Noonan syndrome (NS) related to RAF1 mutations demonstrates that a high proportion of cases exhibit severe lymphatic dysplasia and congenital...
Phenotype analysis of the Noonan syndrome (NS) related to RAF1 mutations demonstrates that a high proportion of cases exhibit severe lymphatic dysplasia and congenital heart disease, especially hypertrophic cardiomyopathy. Because of the difficulty of fetal phenotypic assessment, the percentage of cases with multisystemic prenatal presentation as well as the phenotypic variability may be underestimated. We describe a 35 weeks male preterm infant presenting with de novo missense mutation NM_002880.4(RAF1):c.770C>T (p.Ser257Leu), whose death occurred following birth. Antenatal ultrasound showed polyhydramnios, severe ascites, and tongue protrusion. Autopsy revealed multiple congenital anomalies including intrauterine growth restriction, hydrops fetalis, characteristic facial dysmorphia, short and webbed neck, hypertrichosis, severe lungs hypoplasia, thymic hyperplasia, hepato-splenomegaly, bilateral mild uretero-hydronephrosis, and mild pontocerebellar hypoplasia. Histology revealed increased hepatic hematopoiesis and iron deposits. This report confirms that NS may be associated with multisystem involvement and provides further evidence for the wide phenotypic variability associated with RAF1 variants.
Topics: Infant, Newborn; Humans; Male; Female; Pregnancy; Proto-Oncogene Proteins c-raf; Infant, Premature; Heart Defects, Congenital; Noonan Syndrome; Hydrops Fetalis; Phenotype
PubMed: 36333975
DOI: 10.1002/ajmg.a.63035 -
Traffic Injury Prevention 2023In rear impacts, the seat and seatbelt are intended to provide occupant restraint and maintain the occupant on the seat with favorable kinematics and low biomechanical...
OBJECTIVE
In rear impacts, the seat and seatbelt are intended to provide occupant restraint and maintain the occupant on the seat with favorable kinematics and low biomechanical responses. This study analyzes the lack of restraint provided by lap-shoulder belts in rear impacts with and without pretensioning and offers thoughts on ways to provide early restraint by seatbelts.
METHODS
Rear sled tests were conducted at 40.2 km/h (25 mph) delta V with a lap-shoulder belted, instrumented 50th Hybrid III. The dummy instrumentation included head, chest and pelvis triaxial acceleration and upper and lower neck triaxial loads and moments. Lap and shoulder belt loads were measured. High-speed video recorded different views of the occupant kinematics. In the first series, two sled tests were conducted with a Ford F-150 driver seat. One test was with the standard lap-shoulder belts only and a second with buckle pretensioner activation. In the second series, three matched tests were conducted with a Ford Escape driver seat. One test was with the lap-shoulder belts only, a second with retractor and anchor pretensioning and a third with only retractor pretensioning. The analysis included occupant kinematics, lap-belt movement and estimation of the load on the occupant's torso. The load was the sum of force on the upper and lower torso. The upper torso mass was 30.8 kg (67.8 lb) based on GEBOD data for the 50th Hybrid III. It was multiplied by the resultant chest acceleration to calculate the upper torso force. The lower-torso mass was 30.9 kg (68.0 lb). It was multiplied by the resultant pelvic acceleration to calculate the lower torso force. The total load on the seatback was the sum of the upper and lower torso force. The change in angle (θ) of the lap belt was determined by video analysis. The angle θ was from the horizontal up to a line through the lap-belt webbing. Ways to provide early lap-belt restraint were considered.
RESULTS
The rear sled testing at 40.2 km/h (25 mph) showed that the seatbelt provided essentially no restraint of the rearward movement of the occupant. The seat provided essentially all of the rearward restraint with and without pretensioning. There was minimal lap belt load in the series with the dual recliner Escape seat, except for a spike caused by pretensioning. There was more seat deformation in the tests with the single-side recliner F-150 seat. There were higher belt loads. The lap belt limited the lifting of the hips and thighs with essentially no rearward restraint of the occupant. Tension in the lap belt did not relate to restraint of rearward movement of the occupant. Seatbelts provided forward restraint of the occupant during rebound with the belts providing noticeable deceleration of the chest and pelvis. Concepts were considered to provide early lap-belt restraint. One involved a rear pretensioner that dynamically moves the lap-belt anchor forward and upward while tightening the belts in a rear impact. This provides a lap-belt angle greater than θ = 90 deg before occupant movement. With this geometry, the lap belt restrains rearward movement of the occupant and pulls the hip down early in a rear impact.
CONCLUSION
Seatbelts and pretensioners were designed for occupant restraint in frontal crashes, so it is not a surprise they do not provide much restraint of an occupant in rear impacts up to 40.2 km/h (25 mph). The lack of early lap-belt restraint is due to the unfavorable belt angle from the anchors over the hip. A concept is discussed that dynamically moves the anchors in rear impacts to provide early belt restraint.
Topics: Humans; Accidents, Traffic; Seat Belts; Thorax; Neck; Movement; Biomechanical Phenomena; Equipment Design; Acceleration
PubMed: 36135987
DOI: 10.1080/15389588.2022.2121143 -
PeerJ 2022Mesosaurs are the first secondarily aquatic amniotes and one of the most enigmatic clades of reptiles from the early Permian. They have long puzzled paleontologists with...
Mesosaurs are the first secondarily aquatic amniotes and one of the most enigmatic clades of reptiles from the early Permian. They have long puzzled paleontologists with their unique morphologies: possessing an elongated skull with thin needle-like teeth, a long neck, large webbed hindlimbs, banana-shaped pachyosteosclerotic ribs, and a long tail. Here, we look at a large dataset of morphometric measurements from 270 mesosaur specimens in collections around the world. These measurements characterize skull, tooth, and limb proportions and their variation with size. This data presents evidence of surprising ontogenetic changes in these animals as well as new insights into their taxonomy. Our results support the recent hypothesis that is the only valid species within Mesosauridae and suggest that "" and "" represent immature stages or incomplete specimens of by showing that all three species occupy an incomplete portion of the overall size range of mesosaurs. Under the single-species hypothesis, we highlight a number of ontogenetic trends: (1) a reduction in skull length accompanied by an elongation of the snout within the skull, (2) an elongation of teeth, (3) a reduction in hind limb length, and (4) a reduction in manus length. Concurrent with these changes, we hypothesize that mesosaurs went through a progressive ecological shift during their growth, with juveniles being more common in shallow water deposits, whereas large adults are more frequent in pelagic sediments. These parallel changes suggest that mesosaurs underwent a diet and lifestyle transition during ontogeny, from an active predatory lifestyle as juveniles to a more filter-feeding diet as adults. We propose that this change in lifestyle and environments may have been driven by the pursuit of different food sources, but a better understanding of the Irati Sea fauna will be necessary to obtain a more definitive answer to the question of young mesosaur diet.
Topics: Animals; Skull; Reptiles; Tooth; Head; Diet
PubMed: 36132215
DOI: 10.7717/peerj.13866 -
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 -
A&A Practice Aug 2022Features of Noonan syndrome include a distinctive facial appearance, short stature, a broad or webbed neck, congenital heart disease, bleeding problems, skeletal...
Features of Noonan syndrome include a distinctive facial appearance, short stature, a broad or webbed neck, congenital heart disease, bleeding problems, skeletal malformations, and developmental delay. Although pulmonary stenosis is most commonly reported, up to 20% of patients have hypertrophic cardiomyopathy (HCM). We report the use of a combined spinal-caudal epidural anesthesia technique during urologic surgery (pyeloplasty) in an 8-week-old infant with Noonan syndrome and HCM. A spinal-caudal epidural technique provides favorable hemodynamic conditions, avoids the need for airway instrumentation, and may serve as an alternative to general anesthesia in these high risk patients.
Topics: Anesthesia, Epidural; Anesthesia, Spinal; Cardiomyopathy, Hypertrophic; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Noonan Syndrome
PubMed: 35952335
DOI: 10.1213/XAA.0000000000001611 -
BMC Nephrology Feb 2022Nutcracker syndrome (NCS) is characterized by compression of the left renal vein (LRV) between the aorta and the superior mesenteric artery. While rare, NCS was reported...
BACKGROUND
Nutcracker syndrome (NCS) is characterized by compression of the left renal vein (LRV) between the aorta and the superior mesenteric artery. While rare, NCS was reported to be accompanied by double inferior vena cava (IVC). We herein report a case of Noonan syndrome (NS) with double IVC who presented with macrohematuria and proteinuria.
CASE PRESENTATION
The patient was a 23-year-old man, who had been diagnosed with NS due to RIT1 mutation, after showing foamy macrohematuria 3 weeks previously. A physical examination revealed low-set ears and a webbed neck. A urinalysis showed hematuria and proteinuria, and urinary sediments showed more than 100 isomorphic red blood cells per high-power field. His proteinuria and albuminuria concentrations were 7.1 and 4.5 g/g⋅Cr, respectively. Three-dimensional contrast-enhanced computed tomography (CT) showed double IVC and narrowing of the LRV after interflow of the left IVC. The aortomesenteric angle on a sagittal reconstruction of the CT image was 14.7°. Cystoscopy revealed a flow of macrohematuria from the left ureteral opening. On Doppler ultrasonography, there was scant evidence to raise the suspicion of the nutcracker phenomenon. Since severe albuminuria continued, a left kidney biopsy was performed. Light microscopy showed red blood cells in Bowman's space and the tubular lumen. Electron microscopy revealed disruption of the glomerular basement membrane (GBM). Vulnerability of the GBM was suspected and a genetic analysis revealed a heterozygous mutation at c.4793 T > G (p.L1598R) in the COL4A3 gene. Screening for coagulation disorders revealed the factor VIII and von Willebrand factor (vWF) values were low, at 47.6 and 23%, respectively. A multimer analysis of vWF showed a normal multimer pattern and he was diagnosed with von Willebrand disease type 1. As the bleeding tendency was mild, replacement of factor VIII was not performed. His macrohematuria and proteinuria improved gradually without treatment, and his urinalysis results have been normal for more than 6 months.
CONCLUSIONS
The present case showed macrohematuria and proteinuria due to NCS in NS with double IVC and von Willebrand disease type 1. The macrohematuria and proteinuria originated from glomerular hemorrhage because of vulnerability of the GBM due to COL4A3 mutation.
Topics: Autoantigens; Collagen Type IV; Glomerular Basement Membrane; Hematuria; Humans; Male; Mutation; Noonan Syndrome; Proteinuria; Renal Nutcracker Syndrome; Vena Cava, Inferior; Young Adult; von Willebrand Disease, Type 1
PubMed: 35151252
DOI: 10.1186/s12882-022-02671-4 -
Frontiers in Medicine 2021Noonan syndrome (NS) is an autosomal dominant multisystem disorder caused by the dysregulation of the Rat Sarcoma/Mitogen-activated protein kinase (RAS/MAPK) pathway and...
Noonan syndrome (NS) is an autosomal dominant multisystem disorder caused by the dysregulation of the Rat Sarcoma/Mitogen-activated protein kinase (RAS/MAPK) pathway and characterized by short stature, heart defects, pectus excavatum, webbed neck, learning disabilities, cryptorchidism, and facial dysmorphia. Villonodular synovitis is a joint disorder most common in young adults characterized by an abnormal proliferation of the synovial membrane. Multifocal Villonodular synovitis is a rare disease whose recurrent nature can make its management particularly difficult. Currently, there is no systemic therapy recommended in diffuse and recurrent forms, especially because of the fear of long-term side effects in patients, who are usually young. Yet, tyrosine kinase inhibitors seem promising to reduce the effects of an aberrant colony stimulating factor-1 (CSF-1) production at the origin of the synovial nodule proliferation. We present here the case of a 21-year-old woman with NS associated to diffuse multifocal villonodular synovitis (DMVS). Our clinical case provides therapeutic experience in this very rare association. Indeed, in association with surgery, the patient improved considerably: she had complete daily life autonomy, knee joint amplitudes of 100° in flexion and 0° in extension and was able to walk for 10 min without any technical assistance. To our knowledge, this is the first case of a patient suffering from DMVS associated with a Noonan syndrome treated with Glivec (oral administration at a dosage of 340 mg/m in children, until disease regression) on a long-term basis.
PubMed: 35111788
DOI: 10.3389/fmed.2021.817873 -
Journal of Medical Case Reports Dec 202149XXXXY syndrome is the rarest X chromosome aneuploidy, with approximate incidence of 1:85,000-100,000 male births. Worldwide, around 100 cases have been reported. In...
BACKGROUND
49XXXXY syndrome is the rarest X chromosome aneuploidy, with approximate incidence of 1:85,000-100,000 male births. Worldwide, around 100 cases have been reported. In this report, we describe one such case seen in Sri Lanka.
CASE PRESENTATION
A 10-day-old Sri Lankan neonate born in a tertiary care center was referred to the pediatric endocrinology unit of Lady Ridgeway Hospital due to detection of ambiguous genitalia at birth. He was the first child born to nonconsanguineous healthy parents following an uncomplicated antenatal period. He was born at term via normal vaginal delivery, with a birth weight of 2.385 kg. The baby was active, and there was no documented hypoglycemia or alteration in basic biochemical investigations. On examination, the child had hypertelorism, upslanting palpebral fissures, flat occiput, and mild webbing of the neck. System examination was normal. Genitalia examination revealed bifid scrotum, perineal urethra, 2 cm phallus, and bilateral testis in situ. Hormonal analysis, including dehydroepiandrosterone sulfate, testosterone, and 17-OH progesterone levels, was normal except for an elevated level of follicle-stimulating hormone, indicating gonadal dysgenesis. Ultrasound of the abdomen detected testis located at bilateral inguinal canal, and no Müllerian structures were visible. Echocardiography showed a small patent foramen ovale with otherwise normal heart. Chromosome analysis revealed 49XXXXY syndrome.
CONCLUSION
49XXXXY syndrome should be entertained as a rare possibility for ambiguous genitalia, and karyotyping is an essential investigation for evaluation of such patients.
Topics: Child; Disorders of Sex Development; Female; Follicle Stimulating Hormone; Humans; Infant; Infant, Newborn; Karyotyping; Male; Pregnancy; Testis; Testosterone
PubMed: 34965889
DOI: 10.1186/s13256-021-03188-4 -
Frontiers in Endocrinology 202118q- syndrome is a rare chromosomal disease caused by the deletion of the long arm of chromosome 18. Some cases with 18q- syndrome can be combined with growth hormone... (Review)
Review
BACKGROUND
18q- syndrome is a rare chromosomal disease caused by the deletion of the long arm of chromosome 18. Some cases with 18q- syndrome can be combined with growth hormone deficiency (GHD), but data on the efficacy of recombinant human growth hormone (rhGH) treatment in 18q- syndrome are limited.
METHODS
Here, we report one case of 18q- syndrome successfully treated with long-term rhGH supplement. Previously reported cases in the literature are also reviewed to investigate the karyotype-phenotype relationship and their therapeutic response to rhGH.
RESULTS
A 7.9-year-old girl was referred for evaluation for short stature. Physical exam revealed proportionally short stature with a height of 111.10 cm (-3.02 SD score (SDS)), low-set ears, a high-arched palate, a small jaw, webbed neck, widely spaced nipples, long and tapering fingers, and cubitus valgus. Thyroid function test indicated subclinical hypothyroidism. The peak value of growth hormone was 10.26 ng/ml in the levodopa provocation test. Insulin-like growth factor 1 (IGF-1) was 126 ng/ml (57-316 ng/ml). Other laboratory investigations, including complete blood cell count, liver and kidney function, gonadal function, serum adrenocorticotropin levels, and serum cortisol levels, were all within normal ranges. Karyotype analysis showed 46, XX, del (18) (q21). L-Thyroxine replacement and rhGH treatment were initiated and maintained in the following 7 years. At the age of 14.8, her height has reached 159.5 cm with a height SDS increase of 2.82 SDS (from -3.02 SDS to -0.20 SDS). No significant side effects were found during the treatment. The literature review indicated the average rhGH treatment duration of 16 patients was 5.9 ± 3.3 years, and the average height SDS significantly increased from -3.12 ± 0.94 SDS to -1.38 ± 1.29 SDS after the rhGH treatment (p < 0.0001).
CONCLUSION
The main clinical manifestations of 18q- syndrome include characteristic appearance, intellectual disability, and abnormal genital development. The literature review suggested a significant height benefit for short stature with 18q- syndrome from long-term rhGH treatment.
Topics: Child; China; Chromosome Deletion; Chromosome Disorders; Chromosomes, Human, Pair 18; Female; Growth Disorders; Human Growth Hormone; Humans; Recombinant Proteins; Time Factors; Treatment Outcome
PubMed: 34956087
DOI: 10.3389/fendo.2021.776835