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Molecular Genetics & Genomic Medicine Mar 2024The MYH3-associated myosinopathies comprise a spectrum of rare neuromuscular disorders mainly characterized by distal arthrogryposis with or without other features like...
BACKGROUND
The MYH3-associated myosinopathies comprise a spectrum of rare neuromuscular disorders mainly characterized by distal arthrogryposis with or without other features like pterygia and vertebrae fusion. CPSKF1B (contractures, pterygia, and spondylocarpotarsal fusion syndrome1B) is the only known autosomal recessiveMYH3-associated myosinopathy so far, with no more than two dozen cases being reported.
MATERIALS AND METHODS
A boy with CPSKF1B was recruited and subjected to a comprehensive clinical and imaging evaluation. Genetic detection with whole-exome sequencing (WES) was performed on the patient and extended family members to identify the causative variation. A series of in silico and in vitro investigations were carried out to verify the pathogenicity of the two variants of the identified compound heterozygous variation.
RESULTS
The patient exhibited moderate CPSKF1B symptoms including multiarticular contractures, webbed neck, and spondylocarpotarsal fusion. WES detected a compound heterozygous MYH3 variation consisting of two variants, namely NM_002470.4: c.3377A>G; p. (E1126G) and NM_002470.4: c.5161-2A>C. It was indicated that the NM_002470.4: c.3377A>G; p. (E1126G) variant mainly impaired the local hydrogen bond formation and impacted the TGF-B pathway, while the NM_002470.4: c.5161-2A>C variant could affect the normal splicing of pre-mRNA, resulting in the appearance of multiple abnormal transcripts.
CONCLUSIONS
The findings of this study expanded the mutation spectrum of CPSKF1B, provided an important basis for the counseling of the affected family, and also laid a foundation for the functional study of MYH3 mutations.
Topics: Humans; Male; Arthrogryposis; Conjunctiva; Contracture; Family; Pterygium
PubMed: 38444278
DOI: 10.1002/mgg3.2401 -
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 -
Heliyon Jan 2024Brachyolmia is a heterogeneous group of developmental disorders characterized by a short trunk, short stature, scoliosis, and generalized platyspondyly without...
Brachyolmia is a heterogeneous group of developmental disorders characterized by a short trunk, short stature, scoliosis, and generalized platyspondyly without significant deformities in the long bones. DASS (Dental Abnormalities and Short Stature), caused by alterations in the gene, was previously considered as a subtype of brachyolmia. The present study investigated three unrelated consanguineous families (A, B, C) with Brachyolmia and DASS from Egypt and Pakistan. In our Egyptian patients, we also observed hearing impairment. Exome sequencing was performed to determine the genetic causes of the diverse clinical conditions in the patients. Exome sequencing identified a novel homozygous splice acceptor site variant (:c.3629-1G > T; p. ?) responsible for DASS phenotypes and a known homozygous missense variant (: c.590T > C; p.Ile197Thr) causing hearing impairment in the Egyptian patients. In addition, two previously reported homozygous frameshift variants (:c.132delG; p.Pro45Argfs*25) and (:c.2216delG; p.Gly739Alafs*7) were identified in Pakistani patients. This study emphasizes the vital role of in the axial skeleton and tooth morphogenesis and expands the mutational spectrum of . We are reporting variants in seven patients of three families, majorly causing brachyolmia with dental and cardiac anomalies. Skeletal assessment documented short webbed neck, broad chest, evidences of mild long bones involvement, short distal phalanges, pes planus and osteopenic bone texture as additional associated findings expanding the clinical phenotype of DASS. The current study reveals that the hearing impairment phenotype in Egyptian patients of family A has a separate transmission mechanism independent of .
PubMed: 38192829
DOI: 10.1016/j.heliyon.2023.e23688 -
Cureus Oct 2023Turner syndrome (TS) is a genetic anomaly that is characterized by the absence of an X chromosome, either completely or partially. Primary amenorrhea, short stature,...
Turner syndrome (TS) is a genetic anomaly that is characterized by the absence of an X chromosome, either completely or partially. Primary amenorrhea, short stature, webbed neck, cubitus valgus, and a little intellectual disability are some of the characteristics. Infertility is also one of the most common clinical symptoms of TS-affected females. With the advent of assisted reproductive technology (ART), chances of childbearing possibilities for TS females have risen. Infertility issues in females with TS are challenging, but they can be managed with proper counseling and ART by artificial implantation, oocyte donation, and others. This case report aims to present the case of a 27-year-old female who had not attained her menarche and wanted to conceive. She was diagnosed with TS on the basis of clinical and laboratory investigations. The patient was, thereafter, treated for infertility by oocyte donation and conceived successfully.
PubMed: 38022282
DOI: 10.7759/cureus.47172 -
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 -
Clinical Case Reports Jul 2023Lethal multiple pterygium syndrome is a very rare genetic disorder. The manifestations of this condition include growth deficiency of the fetus, craniofacial anomalies,...
Lethal multiple pterygium syndrome is a very rare genetic disorder. The manifestations of this condition include growth deficiency of the fetus, craniofacial anomalies, joint contracture, and skin webbing (pterygia). This disorder is fatal before birth or shortly after birth. We reported a case of lethal multiple pterygium syndrome with multiple anomalies including pterygia involving the axilla, bilateral antecubital fossa, and groin. Arthrogryposis involving multiple lower and upper extremities joints. Cleft palate, microstomia and limitation of mouth opening, webbed neck, asymmetric small and narrow chest, ambiguous genitalia, depressed and wide nasal bridge, antemongoloid slant, low-set, malformed, and posteriorly rotated ears, pterygia, syndactyly and camptodactyly of hands and rocket bottom feet. LMPS is a congenital genetic disease with multiple anomalies that is fatal in the second and third trimesters of pregnancy or shortly after birth. With genetic testing and counseling, it can be prevented from recurring in subsequent pregnancies.
PubMed: 37448946
DOI: 10.1002/ccr3.7678 -
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 -
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 -
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