Multiple Systemic Malformations Research Articles

Surgical treatment for congenital vertebral anomalies with bilateral bifid intrathoracic rib in association: A series of five cases.

Congenital scoliosis is often associated with costal deformities, of which a bilateral bifid intrathoracic rib is very rare. The aim of this study was to retrospectively summarize the clinical manifestations, imaging characteristics, treatment strategies, and postoperative outcomes of five patients with bilateral bifid intrathoracic rib. We retrospectively reviewed the imaging findings and medical records of five pediatric patients (two girls, three boys) with bilateral bifid intrathoracic rib who were surgically treated for congenital kyphoscoliosis (mean age = 8 years). The clinical manifestations, imaging characteristics, treatment strategies, and postoperative outcome were summarized. Four of five patients showed abnormalities from birth. All five patients presented with kyphoscoliosis and a fused vertebral body or lamina. The bilateral bifid intrathoracic rib was located at T2-3 in three patients, T7 in one patient, and T10 in one patient. Various congenital spinal deformities and multiple system malformations were present in all five patients. Three patients had preoperative neurological deficits. For corrective surgery, one patient received a traditional growing rod implantation, one patient underwent resection of a bony septum, and three patients underwent spinal osteotomy. One patient suffered complete paralysis of the lower limbs after surgery. Bilateral bifid intrathoracic rib is a rare anomaly that typically occurs in patients with serious kyphoscoliosis. Bilateral bifid intrathoracic rib patients show similar clinical and radiological characteristics and are likely to exhibit neurological deficits before or following corrective surgery. Spinal surgeons should be aware of the high risk of permanent neurological complications related to surgery in these patients. level IV.

Sex-specific difference in phenotype of Kabuki syndrome type 2 patients: a matched case-control study.

Kabuki syndrome (KS) is a monogenic disorder leading to special facial features, mental retardation, and multiple system malformations. Lysine demethylase 6A, (KDM6A, MIM*300128) is the pathogenic gene of Kabuki syndrome type 2 (KS2, MIM#300867), which accounts for only 5%-8% of KS. Previous studies suggested that female patients with KS2 may have a milder phenotype. We summarized the phenotype and genotype of KS2 patients who were diagnosed in Shanghai Children's Medical Center since July 2017 and conducted a 1:3 matched case-control study according to age and sex to investigate sex-specific differences between patients with and without KS2. There were 12 KS2 cases in this study, and 8 of them matched with 24 controls. The intelligence quotient (IQ) score of the case group was significantly lower than that of the control group (P < 0.001). In addition, both the incidence of intellectual disability (ID) (IQ < 70) and moderate-to-severe ID (IQ < 55) were significantly higher in the case group than those in the control group. No sex-specific difference was found in the incidence of ID or moderate-to-severe ID between the female cases and female controls, whereas there was a significant difference between male cases and male controls. Furthermore, the rate of moderate-to-severe ID and congenital heart disease (CHD) was significantly higher in the male group than that in the female group. Our results showed that a sex-specific difference was exhibited in the clinical phenotypes of KS2 patients. The incidence of CHD was higher in male patients, and mental retardation was significantly impaired. However, the female patients' phenotype was mild.

Kidney complications in 107 Fanconi anemia patients submitted to hematopoietic cell transplantation

Fanconi anemia (FA) is a rare disease characterized by progressive bone marrow failure, cancer predisposition, and multiple systemic malformations, including congenital abnormalities of the kidney and urinary tract (CAKUT). Hematopoietic cell transplantation (HCT), the only potentially curative treatment for the hematological complications of FA, may precipitate acute kidney injury (AKI) and hypertension. We retrospectively investigated 107 FA patients who underwent HCT between 2009 and 2017. We investigated the incidence and risk factors of AKI within 100 days after HCT in a cohort of FA patients, and kidney function and hypertension over 2-year follow-up.The incidence of AKI (mainly stage I) was 18.7%. Patients aged ≥ 11 years at transplantation showed a higher risk of AKI (OR 3.53). The eGFR was 60-90 mL/min/1.73 m2 in 53 (49.5%), 55 (51.4%), 50 (50.5%), 50 (51%), and 46 (59.7%) patients before HCT, at 100 days, 6 months, 1 year, and 2 years. Within the first 100 days after HCT, hypertension was observed in 72% of the patients and was associated with cyclosporine therapy. Most (62.3%) patients had stage 2 hypertension. CAKUT was observed in 33.7% of the patients and was associated with both hypertension (86%) and diminished kidney function but not with AKI.Conlusion: Although AKI, a commonly known HCT complication, was mild in this study, the prevalence of chronic kidney disease (CKD), as well as the high incidence of hypertension, specially associated with CAKUT point out the importance of kidney care in short and long-term follow up of FA patients. What is Known: • Fanconi anemia (FA) is the most frequent inherited bone marrow failure in children, and 30% of cases have congenital anomalies of kidney (CAKUT). • Acute kidney injury and hypertension after hematopoietic cell transplantation (HCT) may impact the outcomes.. What is New: • Despite the presence of CAKUT and stage 2 CKD in 33.7% and 50% of the patients, respectively, AKI was mild and transitory after HCT in FA patients. • CAKUT in FA patients was associated with lower kidney function and hypertension after HCT.

Síndrome de Adams-Oliver

A Síndrome de Adams-Oliver é uma desordem rara caracterizada por aplasia cútis congênita e defeitos nos membros distais transversais. Geralmente esporádica, mas também autossômica recessiva ou dominante, apresenta um amplo espectro de apresentações fenotípicas, que podem incluir variadas malformações múltiplas sistêmicas. A doença pode ser fatal, quando inclui principalmente anomalias cardíacas, cerebrais ou renais graves. Acredita-se que a etiopatogenia se dá em função de distúrbios na vasculogênese, e mutações em seis genes foram identificados. Ampla revisão da literatura foi realizada, discutindo critérios diagnósticos e terapêuticos. Por fim, foi relatado o caso de um menino brasileiro de 11 anos de idade, com fenótipo característico e doença leve, sem achados de anomalias sistêmicas, mas retardo mental, epilepsia e traços autistas, com ressonância encefálica normal.

Efficacy of Intravenous Immunoglobulin in a Case of Emanuel Syndrome

We report a case of a male patient with Emanuel syndrome (ES) with multiple systemic malformations. He had frequent recurrent seizures and infectious diseases after six months. Because the level of immunoglobulin (IgG) was below the normal range for his age, he was administered intravenous immuno-globulin (IVIG) whenever infection occurred. As he grew up, the frequency of infections and seizures were reduced after IVIG therapy. Although the mechanism was not identified, IVIG might be effective for not only recurrent infections, but also for reducing recurrent seizures.

Functional variant in methionine synthase reductase intron-1 is associated with pleiotropic congenital malformations.

Congenital malformations, such as neural tube defects (NTDs) and congenital heart disease (CHD), cause significant fetal mortality and childhood morbidity. NTDs are a common congenital anomaly, and are typically induced by higher maternal homocysteine (Hcy) levels and abnormal folate metabolism. The gene encoding methionine synthase reductase (MTRR) is essential for adequate remethylation of Hcy. Previous studies have focused on the coding region of genes involved in one-carbon metabolism, but recent research demonstrates that an allelic change in a non-coding region of MTRR (rs326119) increases the risk of CHD. We hypothesized that this variant might contribute to the etiology of NTDs as well, based on a common role during early embryogenesis. In the present study, 244 neural tube defect cases and 407 controls from northern China were analyzed to determine any association (by χ (2) test) between rs326119 and disease phenotypes. Significant increased risk of anencephaly was seen in MTRR variant rs326119 heterozygote (het) and homozygote (hom) individuals [odds ratios (OR)het=1.81; ORhom=2.05)]. Furthermore, this variant was also a risk factor for congenital malformations of the adrenal gland (OR=1.85), likely due to multiple systemic malformations in the NTDs case population. Our present data indicate that the rs326119 non-coding variant of MTRR has a pleiotropic effect on the development of multiple tissues, especially during early stages in utero. This suggests the allelic state of MTRR is a significant clinical factor affecting Hcy levels and optimal folic supplementation.

Pattern of fetal congenital anomalies among consanguineous marriages in Cairo University Hospitals

Background Congenital anomalies – that is, any malformation that occurs in the developing fetus – is one of the major childhood health problems. Objective The aim of the study was to examine the pattern of fetal congenital anomalies in consanguineous marriages. Participants and methods This cross-sectional study included 150 pregnant women from consanguineous marriages with fetal congenital anomalies. They were recruited from the Fetal Medicine Unit at Cairo University Hospital. A structured interview was conducted to collect data on sociodemographic characteristics, medical history, and past obstetric history. An ultrasonographic examination was performed for anatomical scanning of the fetus to screen for the presence of congenital anomalies, in addition to fetal biometry. Results The central nervous system was the most commonly affected system (44%), followed by the musculoskeletal system (23%). Multiple anomalies were detected in 52.7% of the fetuses; they were significantly more common in first-degree consanguineous marriages (P=0.001). The most common types of congenital anomalies among fetuses from consanguineous marriages were cleft palate, bilateral cleft lip, hydronephrosis, and unilateral cleft lip. Conclusion Multiple-system malformations were significantly associated with first-degree consanguineous marriages.

Chromosomal Abnormalities among Children with Congenital Malformations

Increase in chromosomal abnormalities is reported in patients referred with birth defects and infertility. This study was aimed to carry out chromosomal analysis for the presence of cytogenetic abnormalities among congenitally malformed children. The karyotypic status could be determined in 176 cases of the 195 malformed children studied. Thirty (about 17%) children exhibited chromosomal anomalies. Among 85 cases with multiple system malformations, 32 (37.6%) showed chromosomal abnormalities and all of them belonged to the category of known syndromes. Chromosomal variants were observed in two children. Down syndrome was the most common syndrome encountered. Evaluation of chromosomal abnormalities is important in understanding the etiology of congenital malformations. Further, a correlation does exist between phenotypic features and the karyotype. Variants are in general, not related directly to the phenotype.

Arteriovenous Fistula at Scalp: Rapid Progression After Embolization of Contralateral Facial Arteriovenous Malformation

scalp is an abnormal connection between the feeding arteries and draining veins, without the normal capillary bed in the subcutaneous layer of the scalp. The draining veins may be grossly dilated and tortuous, and may show variceal dilatation (1-5). It is generally thought that AVM arises from multiple developmental defects causing the primitive capillary bed to fail to persist (6, 7). It is also thought that increased arterial pressure and flows lead to opening and dilatation of normal, latent AV shunts. Local ischemia and minor trauma also plays a role in enlargement of arteriovenous fistulas (AVF). Multiple craniofacial AVMs occurring in one patient are extremely rare, and only a few cases with multiple systemic malformations such as hereditary hemorrhagic telangiectasia or RenduOsler-Weber disease have been reported (8). Multiple craniofacial AVM may be hemodynamically related to each other by complex and intercommunicating vascular networks. This report describes a case with two craniofacial AVMs located at anatomically different regions. Interestingly, we found rapid progression of a scalp AVM after embolization of the other AVM on the contralateral side of the face. This may reflect a hemodynamic relationship between the AVMs located at anatomically different regions, and may suggest a new guideline in treatment of multiple craniofacial AVMs.