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Cureus Apr 2024Beckwith-Wiedemann syndrome (BWS) is a rare genomic imprinting disorder that affects multiple systems. Major features can manifest as large birth weight, anterior...
Beckwith-Wiedemann syndrome (BWS) is a rare genomic imprinting disorder that affects multiple systems. Major features can manifest as large birth weight, anterior abdominal wall defects, macroglossia, hyperinsulinism, organomegaly hemihypertrophy, and renal abnormalities. Characteristic facies manifested as midface hypoplasia, infraorbital creases, facial nevus simplex, and anterior linear ear lobe creases/posterior helical ear pits, with a predisposition to tumor development. This case report describes a Saudi infant born at 38+5 weeks gestation via elective cesarean section to a 33-year-old G3P2+0 mother, with a family history of type 1 diabetes and Down syndrome. Prenatal ultrasound revealed an anterior abdominal wall defect. Postnatally, the infant exhibited macrosomia, macroglossia, and omphalocele. Genetic testing confirmed paternal disomy of the imprinted region in 11p15.5. The infant underwent successful omphalocele repair but experienced respiratory distress, and seizures on the third day of life. Intubation, ventilation, and antiepileptic treatment were initiated. Subsequent investigations revealed right upper lobe collapse, neonatal seizures on electroencephalogram (EEG), and thin corpus callosum on magnetic resonance imaging (MRI). Feeding difficulties led to elective partial glossectomy at two months of age. During her hospital stay two days post surgery, the infant developed persistent hypoglycemia requiring high glucose infusion rates. Extensive endocrine evaluation revealed high insulin and cortisol levels. Subcutaneous octreotide was administered with minimal response. After 15 days of careful glucose tapering, the infant's blood glucose stabilized, reaching feeding targets. The patient was discharged with follow-up appointments. This comprehensive case highlights the complexity of managing severe relapsing hypoglycemia in an infant with BWS.
PubMed: 38707113
DOI: 10.7759/cureus.57588 -
SAGE Open Medical Case Reports 2024Germline pathogenic variants found in the phosphatase and tensin homolog gene are associated with a range of rare syndromes that collectively fall under the umbrella of...
Germline pathogenic variants found in the phosphatase and tensin homolog gene are associated with a range of rare syndromes that collectively fall under the umbrella of phosphatase and tensin homolog hamartoma tumor syndromes. Due to the wide array of possible clinical presentations and the varying degrees of symptom severity, many individuals with phosphatase and tensin homolog hamartoma tumor syndromes might remain undiagnosed for an extended period. We describe a case of a male child who received the diagnosis at the age of 12. His clinical features included macrocephaly, hypertrophy in the left arm, thyroid nodules, penile freckles, developmental delay, and an autism spectrum disorder. Whole exome sequencing revealed a de novo heterozygous variant in the phosphatase and tensin homolog. The case highlights the diverse and complex nature of phosphatase and tensin homolog hamartoma tumor syndromes, emphasizing the necessity for early diagnosis, multidisciplinary care, and surveillance protocols, offering the potential for improved prognostic outcomes and enhanced quality of life for affected individuals.
PubMed: 38585419
DOI: 10.1177/2050313X241245317 -
Frontiers in Pediatrics 2024Fetal Wilms tumor (WT) is extremely rare, but with advances in fetal imaging, more cases are being reported. The management of these cases remains challenging. Herein,...
Fetal Wilms tumor (WT) is extremely rare, but with advances in fetal imaging, more cases are being reported. The management of these cases remains challenging. Herein, we present the case of a full-term female infant diagnosed antenatally at 32 weeks of gestation with a right solid renal mass detected on routine prenatal ultrasound without polyhydramnios. At birth, the infant was healthy, with no evidence of dysmorphic features or abnormal laboratory tests to suggest a predisposition syndrome. Her family history was also unremarkable. A successful radical right nephrectomy was performed on day 2 of life revealing a classic WT. She received vincristine as adjuvant chemotherapy without any complications. At the age of 1 month, the infant developed isolated lateralized overgrowth of the right lower limb suspicious of Beckwith-Wiedemann syndrome. At the latest follow-up of 4 years, the child is healthy and disease-free with conserved asymmetry of lower limbs. The case provides insights into the challenging diagnosis and treatment of fetal WT. A review of the literature suggests that the presence of polyhydramnios is a worse prognostic factor while the combination of best supportive care and surgery remains the best management. Fetal WT can be associated with predisposition syndromes; however, their first manifestations can develop after the diagnosis of cancer has been made, as in our patient. We propose starting active surveillance programs and genetic testing for any case of fetal WT.
PubMed: 38562132
DOI: 10.3389/fped.2024.1334544 -
Surgical Case Reports Mar 2024Beckwith-Wiedemann syndrome (BWS) is a genomic imprinting disorder caused by diverse genetic and/or epigenetic disorders of chromosome 11p15.5. BWS presents with a...
BACKGROUND
Beckwith-Wiedemann syndrome (BWS) is a genomic imprinting disorder caused by diverse genetic and/or epigenetic disorders of chromosome 11p15.5. BWS presents with a variety of clinical features, including overgrowth and an increased risk of embryonal tumors. Notably however, reports of patients with BWS and breast tumors are rare, and the association between these conditions is still unclear. Insulin-like growth factor-2 (IGF2) expression is known to be associated with the development of various cancers, including breast cancer, and patients with BWS with specific subtypes of molecular defects are known to show characteristic clinical features and IGF2 overexpression.
CASE PRESENTATION
A 17-year-old girl who had been diagnosed with BWS based on an umbilical hernia, hyperinsulinemia, and left hemihypertrophy at birth, visited our department with a gradually swelling left breast. Her left breast was markedly larger than her right breast on visual examination. Imaging examinations showed two tumors measuring about 10 cm each in the left breast, and she was diagnosed with juvenile fibroadenoma following core needle biopsy. The two breast tumors were removed surgically and the patient remained alive with no recurrence. The final diagnosis was juvenile fibroadenoma without malignant findings. Immunohistochemical staining using IGF2 antibody revealed overexpression of IGF2 in the cytoplasm of ductal epithelial cells. Because of her clinical features and IGF2 overexpression, molecular defects of 11p15.5 including a possible genetic background of paternal uniparental disomy of chromosome 11 or hypermethylation of imprinting center 1 was suspected.
CONCLUSIONS
In this case, overexpression of IGF2 suggested a possible relationship between BWS and breast tumors. Moreover, the characteristic clinical features and IGF2 staining predicted the subtype of 11p15.5 molecular defects in this patient.
PubMed: 38514513
DOI: 10.1186/s40792-024-01865-2 -
Translational Cancer Research Feb 2024Nephron sparing surgery (NSS) had become the main surgical treatment for bilateral nephroblastoma. But it remained a challenge for surgeons to balance the dilemma...
BACKGROUND
Nephron sparing surgery (NSS) had become the main surgical treatment for bilateral nephroblastoma. But it remained a challenge for surgeons to balance the dilemma between complete tumor resection to reduce tumor recurrence and renal parenchyma preservation to reduce end-stage renal disease (ESRD). In this study, we summarized our clinical experience for bilateral Wilms tumors managed in our center and evaluated the influence of different surgical approaches on prognosis.
METHODS
The clinical data of patients with bilateral Wilms tumor in our hospital from January 2010 to December 2020 were retrospectively analyzed, and the clinical symptoms, surgical approaches and prognosis of the disease were summarized.
RESULTS
We reviewed medical records of 16 patients, including 13 (81.3%) girls and 3 (18.7%) boys. The mean age of the patients was 17.88±11.65 months (range, 6-42 months). Five patients presented with hypertension and two presented with hemihypertrophy. Fifteen cases had synchronous tumors, while only one patient had metachronous bilateral lesions. Thirteen patients received neoadjuvant chemotherapy and only 8 kidneys (30.8%) responded to chemotherapy. Two patients gave up surgery, and the other fourteen patients underwent radical resection, of which 2 patients only underwent unilateral radical nephrectomy (RN); 7 and 5 patients underwent single-stage and two-stage operation for bilateral lesions, respectively. In all surgical patients, RN was performed on 5 kidneys, and NSS was performed on 21 kidneys. The positive margins after NSS were found in 6 kidneys (35.3%). After a median follow-up period of 26.3 months, local tumor recurrence and renal insufficiency occurred in two and one patients. The 5-year overall and event-free survival rates were 78.1% and 58.6%, respectively. In univariable analysis, the survival rate in the initial chemotherapy group (92.3%) was significantly higher than that in the initial surgery group (33.3%) (P=0.048), whereas positive margin and staged operation (P>0.05) appeared not significantly associated with overall survival.
CONCLUSIONS
The proportion of tumor reduction after preoperative chemotherapy is relatively low for bilateral Wilms tumor, but preoperative chemotherapy could improve overall survival. NSS is recommended for bilateral Wilms tumor, and the customized procedure can be selected according to the location and anatomical features of tumor.
PubMed: 38482402
DOI: 10.21037/tcr-23-1428 -
Frontiers in Pediatrics 2024Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by a mutation in either of the two tumor suppressor genes, and . Due to dysregulated activity...
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by a mutation in either of the two tumor suppressor genes, and . Due to dysregulated activity of the mammalian target of rapamycin (mTOR) pathway, hamartomas or benign tumors frequently occur in many organs and are often treated with mTOR inhibitors. Hemihypertrophy is a rare complication of TSC. Although not being a tumor, progressive overgrowth of the affected limb may cause cosmetic and functional problems, for which the efficacy of mTOR inhibitors has not been reported previously. We herein report a case of TSC-associated hemihypertrophy. In this case, genetic studies revealed C loss of heterozygosity as the cause of hemihypertrophy. Clinically, pharmacological treatment with an mTOR inhibitor sirolimus successfully ameliorated cosmetic and functional problems with no intolerable adverse effects.
PubMed: 38455392
DOI: 10.3389/fped.2024.1333064 -
Clinical Case Reports Feb 2024The gain-of-function c.49G>A variant causes hypoketotic hypoglycemia with variable associated features. Due to lack of effective medications, treatment is primarily...
KEY CLINICAL MESSAGE
The gain-of-function c.49G>A variant causes hypoketotic hypoglycemia with variable associated features. Due to lack of effective medications, treatment is primarily supportive. This report suggests waxy maize heat is a viable treatment option.
ABSTRACT
The serine-threonine kinase AKT2 is a critical mediator of insulin's anabolic effects, particularly cellular glucose uptake. The gain-of-function c.49G>A, p.(Glu17Lys) variant results in hypoketotic hypoglycemia with suppressed insulin and free fatty acid levels due to constitutive activation of the insulin signaling cascade. Although biochemical similarities exist among the eight individuals identified to date, the associated phenotype varies considerably. Treatment of these patients remains challenging, consisting primarily of frequent feeds with uncooked cornstarch. We describe a female with hemihypertrophy, developmental delay, and dysmorphic features who presented to our center with hypoglycemic seizures at age 6 months. Critical sample revealed hypoketotic hypoglycemia, undetectable insulin, and suppressed free fatty acids. Molecular testing confirmed a pathogenic c.49G>A, p.(Glu17Lys) mutation. Glycemic control was initially difficult to establish, with recurrent hypoglycemia despite high glucose infusion rates. Following in-hospital administration of waxy maize heat-modified starch at age 4-years, she remained euglycemic overnight, despite a previous report showing no benefit compared to uncooked cornstarch in an infant with the same mutation. Our report suggests waxy maize heat-modified starch is a viable treatment option for patients with activating c.49G>A mutations and provides further evidence of a broad phenotypic spectrum.
PubMed: 38344362
DOI: 10.1002/ccr3.8473 -
Clinical Case Reports Feb 2024Lipid hemihypertrophy should be considered in the differential diagnosis of neonatal asymmetry. Early recognition and further evaluation for associated disorders are...
KEY CLINICAL MESSAGE
Lipid hemihypertrophy should be considered in the differential diagnosis of neonatal asymmetry. Early recognition and further evaluation for associated disorders are important for appropriate management and surveillance of potential complications.
ABSTRACT
We present the case of a 5-day-old female neonate who presented with a visibly enlarged right thigh, right labia majora, and below the right mandible. This case report highlights the importance of early identification, comprehensive evaluation, and multidisciplinary management in neonates with lipid hemihypertrophy to optimize their long-term outcomes and quality of life.
PubMed: 38333663
DOI: 10.1002/ccr3.8476 -
Frontiers in Pediatrics 2024Klippel-Trénaunay syndrome, a kind of congenital limb-length-discrepancy disorder, is commonly associated with a variety of vascular anomalies.
BACKGROUND
Klippel-Trénaunay syndrome, a kind of congenital limb-length-discrepancy disorder, is commonly associated with a variety of vascular anomalies.
CASE PRESENTATION
We present the case of a three-day-old newborn with a profound abdominal mass lesion during prenatal magnetic resonance imaging (MRI) examination. After delivery, physical examination revealed mild hemihypertrophy of the left lower extremity and red lesions on the left thigh. MRI of the abdomen showed a cyst-like lesion measuring 6.3 cm × 2.7 cm × 5.5 cm in the upper abdomen. Within the mass, there were also some possible calcified spots exhibiting high T1WI signals and low T2WI signals. A computed tomography (CT) scan of the abdomen was consistent with an ill-defined cystic tumor with small calcifications and encasement of mesenteric vessels. A MRI of the left lower extremity showed a tubular structure with a signal void and homogeneous strong enhancement located in the anterior subcutis of the left lower limb. The CT scan confirmed that the tubular structure was consistent with a venous malformation. This patient had features of Klippel-Trénaunay syndrome, including port-wine stains, a profound abdominal mass, and vascular malformations of the left lower extremity.
CONCLUSIONS
In this article, we presented a case of Klippel-Trénaunay syndrome, emphasizing both prenatal and confirmatory postnatal cross-sectional imaging findings. The rare presentation of an abdominal lymphatic-venous formation played a pivotal role as a crucial indicator for an early diagnosis of Klippel-Trénaunay syndrome.
PubMed: 38312923
DOI: 10.3389/fped.2024.1326909