-
Human Genomics Feb 2023Mutations in NF1 gene could cause allelic disorders with clinical spectrum of Neurofibromatosis type 1 to Noonan syndrome. Here, a 7-year-old Iranian girl is described...
BACKGROUND
Mutations in NF1 gene could cause allelic disorders with clinical spectrum of Neurofibromatosis type 1 to Noonan syndrome. Here, a 7-year-old Iranian girl is described with Neurofibromatosis-Noonan syndrome due to a pathogenic variant in NF1 gene.
METHODS
Clinical evaluations were performed along with genetic testing using whole exome sequencing (WES). The variant analysis including pathogenicity prediction was also done using bioinformatics tools.
RESULTS
The chief compliant of the patient was short stature and lack of proper weight gain. Other symptoms were developmental delay, learning disability, inadequate speech skill, broad forehead, hypertelorism, and epicanthal folds, low set ears and webbed neck. A small deletion, c.4375-4377delGAA, was found in NF1 gene using WES. This variant was classified as pathogenic according to ACMG.
CONCLUSIONS
NF1 variants may show variable phenotypes among the patients; identifying such variants is helpful in therapeutic management of the disease. WES is considered as an appropriate test to diagnose Neurofibromatosis-Noonan syndrome.
Topics: Humans; Genes, Neurofibromatosis 1; Iran; Mutation; Neurofibromatoses; Neurofibromatosis 1; Noonan Syndrome; Female; Child
PubMed: 36803953
DOI: 10.1186/s40246-023-00460-0 -
European Journal of Medical Genetics Feb 2023Noonan syndrome is characterized by variable phenotypic expressivity with characteristic dysmorphic facial features, varying degrees of intellectual disability,...
Noonan syndrome is characterized by variable phenotypic expressivity with characteristic dysmorphic facial features, varying degrees of intellectual disability, developmental delay, short stature, and congenital heart defects in 50-80%. Other findings include a webbed neck, cryptorchidism, coagulation defects and eye abnormalities. Thus far, Noonan syndrome has mainly been attributed to heterozygous pathogenic variants in 10+ different genes, with the rare exception of cases due to biallelic pathogenic variants in LZTR1. Recently, homozygous loss-of-function variants in SPRED2 have been identified as a cause of a recessive Noonan syndrome-like phenotype. We present the phenotypes of two additional patients with homozygosity for a previously unreported loss-of-function variant in SPRED2, thereby adding relevant clinical information about the recently described Noonan syndrome-like SPRED2-related phenotype.
Topics: Humans; Male; Heart Defects, Congenital; Heterozygote; Homozygote; Intellectual Disability; Noonan Syndrome; Phenotype; Repressor Proteins; Transcription Factors
PubMed: 36608738
DOI: 10.1016/j.ejmg.2023.104695 -
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 -
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 -
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