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Cureus Jan 2024Noonan syndrome is a genetic, developmental disorder characterized by facial deformities, congenital heart defects, webbed neck, wide space nipples, and growth hormone...
Noonan syndrome is a genetic, developmental disorder characterized by facial deformities, congenital heart defects, webbed neck, wide space nipples, and growth hormone deficiencies. We report a case of a 15-year-old female patient who presented to the outpatient department with recurrent puffiness of both eyes, easy fatiguability, and dyspnea on exertion. The condition was associated with bilateral proximal muscular weakness of lower limbs with positive Gower's sign. On examination, the patient had a webbed neck, hypertelorism, a shielded chest, short stature, and a high-arched palate. Thyroid function tests revealed hypothyroidism. Chromosomal analysis revealed 46 XX. After excluding Turner syndrome on karyotyping, Noonan syndrome with hypothyroidism was diagnosed. The patient was started on levothyroxine and referred to a pediatric endocrinologist for further growth and development assessment. Autoimmune hypothyroidism in a patient with Noonan Syndrome is rare; it may occur as a separate entity or have some genetic susceptibility. Further research is needed to determine the association of autoimmune hypothyroidism with Noonan syndrome.
PubMed: 38313927
DOI: 10.7759/cureus.51592 -
Industrial Psychiatry Journal 2020Noonan syndrome is an autosomal dominant, genetic, multisystem disorder with a prevalence of 1 in 1000-2500 live births. Characteristic features of the condition include...
Noonan syndrome is an autosomal dominant, genetic, multisystem disorder with a prevalence of 1 in 1000-2500 live births. Characteristic features of the condition include distinctive myopathic facial features, hypertelorism, short and broad nose, webbed neck, and low set ears. About 10% of the subjects have auditory defects due to sensorineural hearing loss. The patient also has short stature, chest deformity (superior pectus carinatum and inferior pectus excavatum), widely spaced nipples, and delayed puberty. A rare psychiatric manifestation of somnambulism and somniloquy in a case of Noonan syndrome is reported.
PubMed: 34158723
DOI: 10.4103/ipj.ipj_84_19 -
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 -
International Journal of Environmental... Aug 2023The objective of this study was to investigate to which extent anatomic features of the nasal and pharyngeal region contribute to the severity of obstructive sleep apnea...
The objective of this study was to investigate to which extent anatomic features of the nasal and pharyngeal region contribute to the severity of obstructive sleep apnea (OSA) and positive airway pressure (PAP) therapy response. Therefore, 93 patients (mean age 57.5 ± 13.0 years, mean body mass index 32.2 ± 5.80 kg/m, 75 males, 18 females) diagnosed with OSA who subsequently started PAP therapy were randomly selected from the databank of a sleep laboratory of a tertiary university medical center. Patients were subdivided based on nasal anatomy (septal deviation, turbinate hyperplasia, their combination, or none of the above), pharyngeal anatomy (webbing, tonsillar hyperplasia, their combination, or none of the above), and (as a separate group) tongue base anatomy (no tongue base hyperplasia or tongue base hyperplasia). Then, polysomnographic data (e.g., arousal index, ARI; respiratory disturbance index, RDI; apnea index, AI; hypopnea index, HI; and oxygen desaturation index, ODI) of diagnostic polysomnography (PSG) and PAP therapy control PSG were collected, grouped, and evaluated. Septal deviation, turbinate hyperplasia, or their combination did not significantly affect the assessed PSG parameters or the response to PAP therapy compared with patients without nasal obstruction ( > 0.05 for all parameters). Accordingly, most PSG parameters and the response to PAP therapy were not significantly affected by webbing, tonsil hyperplasia, or their combination compared with patients without pharyngeal obstruction ( > 0.05 for RDI, AI, HI, and ODI, respectively). However, in the pharyngeal anatomy group, ARI was significantly higher in patients with tonsil hyperplasia ( = 0.018). Further, patients with tongue base hyperplasia showed a significantly higher HI in the diagnostic PSG ( = 0.025) compared with patients with normal tongue base anatomy, but tongue base anatomy did not significantly affect the response to PAP therapy ( > 0.05 for all parameters). The influence of anatomic features of the nasal and pharyngeal region on PAP therapy response appears to be small, and generalizability of these results requires further studies.
Topics: Female; Male; Humans; Adult; Middle Aged; Aged; Hyperplasia; Pharynx; Turbinates; Academic Medical Centers; Arousal
PubMed: 37623166
DOI: 10.3390/ijerph20166580 -
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 -
Forensic Science, Medicine, and... Mar 2022An 89-year-old man involved in a vehicle crash was found at autopsy to have a linear seat belt mark on the right side of his neck associated with extensive injuries of...
An 89-year-old man involved in a vehicle crash was found at autopsy to have a linear seat belt mark on the right side of his neck associated with extensive injuries of the right paraspinal muscles with fracture-dislocation and separation of cervical vertebrae 5 and 6. There was also fracture of the right facet joint between cervical vertebrae 5 and 6 and laceration of the right vertebral artery. Death was due to a cervical seat belt injury with spinal fracture and laceration of the right vertebral artery. The presence of extensive injuries to the right paraspinal muscles and cervical vertebra 5-6 fact joint beneath the seat belt mark would be in keeping with trauma due to the belt webbing, rather than mere hyperextension/flexion of the cervical spine. This report demonstrates a rare form of seat belt injury, transection of the vertebral artery, and suggests that the finding of seat belt markings on the lateral aspect of the neck should prompt examination for this type of lethal vascular injury at autopsy.
Topics: Accidents, Traffic; Aged, 80 and over; Humans; Lacerations; Male; Seat Belts; Spinal Fractures; Vertebral Artery
PubMed: 34655043
DOI: 10.1007/s12024-021-00429-2 -
Cureus Jul 2021Turner syndrome (TS), or Bonnevie-Ullrich syndrome, also known as congenital ovarian hypoplasia syndrome, is the most common sex chromosome abnormality in females in...
Turner syndrome (TS), or Bonnevie-Ullrich syndrome, also known as congenital ovarian hypoplasia syndrome, is the most common sex chromosome abnormality in females in approximately 1 in 2000 live birth. It occurs when the X chromosome is partially or completely missing in females caused by monosomy or structural abnormalities of the X chromosome. It is mainly diagnosed in late childhood or adolescent age and rarely identified during the neonatal period. It is characterized by short stature, webbed neck, lymphedema of extremities, widely spaced-out nipples, and cubital valgus. Early diagnosis of TS allows for appropriate and timely initiation of therapy with comprehensive care. We report a case of a neonate presented with the complaint of edema of feet since birth and syndromic features. TS was diagnosed by the chromosomal analysis, which demonstrated a gene karyotype of 46.X,i(X)(q10){20}.
PubMed: 34513364
DOI: 10.7759/cureus.16733 -
International Medical Case Reports... 2023Lentigines are defined as multiple small pigmented macules measuring up to one centimeter and surrounded by normal-appearing skin, commonly caused by genetic factors....
Lentigines are defined as multiple small pigmented macules measuring up to one centimeter and surrounded by normal-appearing skin, commonly caused by genetic factors. LEOPARD syndrome (LS) is an autosomal dominant distinguished by the presence of several lentigines, with specific phenotypic characteristics that resembles Noonan syndrome (NS). LS is likely to be underdiagnosed or misdiagnosed because many of its symptoms are minor and the accurate diagnosis may be overlooked. Therapy for lentigines are generally aimed at tackling aesthetic disfigurement and its subsequent psychological impacts. This case report aims to highlight the efficacy of 532-nanometer (nm) Q-switched (QS) Nd:YAG laser in treating lentigines in a 21-year-old woman with LS overlap NS. The patient initially came to seek treatment of her facial lentigines. However, some mild abnormalities such as ocular hypertelorism, left eye ptosis, and webbed neck were observed. Hormonal, cardiac, and pulmonary functions were within normal limit. Histopathological results supported the diagnosis of lentigo. The patient was given sunscreen and depigmenting agents and was instructed to apply the medications routinely. The patient then underwent two sessions of 532-nm QS Nd:YAG laser with a 3 mm spot size, 1 J/cm fluence, and a 1 Hz frequency. Objective clinical improvements were observed using spectrophotometer examination, there were no side effects found, and she was satisfied with the results. Dermatologists should play an integral role in establishing the diagnosis and management of systemic syndrome, manifesting specifically as dermatological symptoms. Lentigines in LS last throughout the patient's lifespan. Nd:YAG laser therapy can be effective in treating lentigines with long-lasting results. It plays a role in improving the patient's life quality, especially where the genetic disorder itself is a debilitating condition. The limitation of this case report was the lack of a genetic test, as the suspected diagnosis was made based on clinical symptoms.
PubMed: 37193055
DOI: 10.2147/IMCRJ.S407416 -
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 -
Cureus Nov 2020Turner syndrome (TS) is the most frequent sex abnormality in women. The physical features include short stature, webbing of the neck, and gonadal dysgenesis. Typically,...
Turner syndrome (TS) is the most frequent sex abnormality in women. The physical features include short stature, webbing of the neck, and gonadal dysgenesis. Typically, patients with Turner syndrome exhibit no intellectual disability, and a few cases of TS have been associated with epilepsy. Herein, we present a case of TS with intractable epilepsy. The patient presented with global developmental delay at the age of two and karyotyping revealed mosaicism [45, X/46, X del (X) (q21.1)]. At the age of seven, she had generalized tonic epilepsy as well as several focal-onset seizures. She developed daily seizures, which were refractory to several antiepileptic drugs. Interictal electroencephalography (EEG) revealed multifocal spikes, and ictal EEG revealed shifting foci. She visited our hospital at the age of 13. Her peripheral white blood cells G-band and fluorescence in situ hybridization (FISH) method chromosome with cheek swab examinations revealed 45, X. Her peripheral white blood cell mosaic pattern may have disappeared over time or become indetectable. We treated her with clobazam, and then lamotrigine and valproic acid combination therapy, which resulted in a reduction in the frequency of seizures by approximately 50%. Epilepsy and intellectual disability in this case may be due to the mosaic deletion at Xq21.1. Further analysis of similar cases may provide valuable information for effective therapeutic strategies.
PubMed: 33304697
DOI: 10.7759/cureus.11364