Journal of pediatric genetics最新文献

Bardet-Biedl syndrome (BBS) is a rare ciliopathy affecting multiple organ systems. Patients with BBS are usually diagnosed later in childhood when clinical features of the disease become apparent. In this article, we presented a case of BBS discovered by whole genome sequencing in a newborn with heterotaxy, duodenal atresia, and complex congenital heart disease. Early diagnosis is important not only for prognostication but also to explore ways to mitigate the cone-rod dysfunction and for exploring newer therapies. Our case highlights the importance of a high index of suspicion and the utility of advanced genetic testing to provide an early diagnosis for a rare disease.

Aromatic L-amino acid decarboxylase (AADC) deficiency is a disorder of neurotransmitter synthesis. It presents with psychomotor delay, dystonia, oculogyric crisis, and autonomic features. There is paucity of literature on this disorder. Hence, we are reporting this series with an objective to study profile and outcome of Indian children with AADC deficiency. In this retrospective review, all case records of genetically confirmed cases of AADC deficiency at the pediatric neurology department in a tertiary care hospital, from March 2014 to March 2020, were analyzed. The data were extracted in a predesigned proforma and analyzed. Out of seven cases, five were males. Median age of onset of symptoms was 4 months but median age of diagnosis was 12 months. All of them had developmental delay, oculogyric crisis, dystonia, increased sweating, intermittent fever, feeding and sleep disturbance, irritability, failure to thrive, axial hypotonia with dyskinetic quadriparesis, and normal magnetic resonance imaging (MRI) of brain and electroencephalogram (EEG). All of them were treated with pyridoxal 5-phosphate, trihexyphenidyl and pramipexole and six cases, in addition, were given bromocriptine. One case was additionally treated with selegiline. One case showed good improvement, five showed partial improvement, and one case expired. In conclusion, AADC deficiency should be suspected in any child with dyskinetic quadriparesis, oculogyric crisis, autonomic disturbances like increased sweating, intermittent fever, and sleep disturbance with normal neuroimaging.

Neonatal diabetes mellitus is a single gene defect that results in diabetes mellitus in the first 6 months of life. We report a child who was diagnosed to be hyperglycemic at 13 months of life and assumed to have type 1 diabetes mellitus and started on insulin. The child came to us at 2 and 1/2 years of age. He had exceptionally good blood glucose control. His history revealed that he was symptomatic with a voracious appetite and poor weight gain since the second half of infancy. Genetic testing revealed a heterozygous mutation of the INS gene (the gene that codes for insulin). The condition has autosomal dominant inheritance. Testing the parents revealed that the mother had 7.8% mosaicism for this variant in her lymphocyte DNA. Though this did not alter the management of the patient, it did help in counseling the parents regarding risk of recurrence in future pregnancies.

Surgical correction for scoliosis is undertaken to avoid progression to cardiopulmonary compromise as well as improve the patient's overall quality of life. In this case report, we presented a case of a 14-year-old girl with epidermolysis bullosa simplex and Gitelman's syndrome who underwent posterior spinal fusion for scoliosis. The perioperative planning and intraoperative management of a patient with this unique combination of comorbidities undergoing a complex, high-risk surgical procedure were not previously chronicled in the literature. We detailed the steps undertaken to optimize the patient prior to surgery and the unique intraoperative surgical and anesthetic considerations that led to a successful completion of the surgery and recovery.

The normal development of the heart comprises a highly regulated machinery of genetic events, involving transcriptional factors. Congenital heart disease (CHD), have been associated with chromosomal abnormalities and copy number variants (CNVs). Our goal was to investigate through the multiplex ligation-dependent probe amplification (MLPA) technique, the presence of CNVs in reference genes for normal cardiac development in patients with CHD. GATA4 , NKX2-5 , TBX5 , BMP4 , and CRELD1 genes and 22q11.2 chromosome region were analyzed in 207 children with CHD admitted for the first time in a cardiac intensive care unit from a pediatric hospital. CNVs were detected in seven patients (3.4%): four had a 22q11.2 deletion (22q11DS) (1.9%), two had a GATA4 deletion (1%) and one had a 22q11.2 duplication (0.5%). No patients with CNVs in the NKX2-5 , TBX5 , BMP4 , and CRELD1 genes were identified. GATA4 deletions appear to be present in a significant number of CHD patients, especially those with septal defects, persistent left superior vena cava, pulmonary artery abnormalities, and extracardiac findings. GATA4 screening seems to be more effective when directed to these CHDs. The investigation of CNVs in GATA4 and 22q11 chromosome region in patients with CHD is important to anticipating the diagnosis, and to contributing to family planning.

Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder caused by mutations in any of the genes encoding for the branched-chain keto dehydrogenase (BCKDH) components. This study screened MSUD patients throughout the whole Upper Egypt describing their symptoms, clinical and laboratory findings, genetic studies, and their treatment, with a 6-month follow-up for their responses. Screening identified three children with MSUD. Homozygous mutation in R195Q single nucleotide polymorphism (SNP) within the BCKDHA gene was found with the second MSUD patient. Follow-up for 6 months to assess the treatment regimens and progression of cases demonstrated that early treatment regimens including a dietary restriction of branched-chain amino acids with L-Carnitine administration could prevent MSUD-associated intellectual disabilities. It was concluded that R195Q SNP is pathogenic, and it may cause inherited forms of MSUD in some patients. MSUD cases have rarely been reported; so these findings will be highly useful for future cases of MSUD in the Upper Egyptian population.

Paternal microduplication of 11p14.3-p15.5 causes the clinical manifestations of Beckwith-Wiedemann syndrome (BWS), while microdeletion of 18q23-ter is clinically characterized by short stature, congenital malformations, and developmental delay. We describe a 15-month-old girl presenting with protruding tongue, dysmorphic facial features, moderate developmental delay, umbilical hernia, hypotonia, mild-to-moderate pulmonary hypertension, small patent ductus arteriosus, and mild ventricular septal hypertrophy. Brain magnetic resonance imaging showed mild atrophic changes. Chromosomal analysis revealed 46, XX, add(18)(q23). Fluorescence in situ hybridization using subtelomere 18q and whole chromosome painting 18 showed subtelomere deletion in 18q, and the add segment was not derived from chromosome 18. Microarray-based comparative genomic hybridization detected a 22 Mb duplication of chromosome 11p15.5p14.3 and a 3.7 Mb deletion of chromosome 18q23. The phenotype of the chromosomal rearrangements is probably resulted from a combination of dosage-sensitive genes. Our patient had clinical manifestations of both 18q deletion and BWS.

Charcot-Marie-Tooth 4C is characterized by early-onset, rapid progression, and mainly associated with SH3TC2 gene mutations. We reported a male patient carrying a novel heterozygous nonsense mutation in SH3TC2 gene along with a heterozygous known pathogenic mutation. Symptoms began at 15 months and by 14 years, he presented significant motor impairment. Both parents exhibited one of the mutations in the heterozygous state, while his 8-year-old brother carried the same compound heterozygosity, showing only a mild phenotype. In our case, we discussed the contribution of compound heterozygosity to intrafamilial variability in Charcot-Marie-Tooth and the role of modifying genes.

The study aimed to assess the involvement of three proteasomal genes, PSMA6 , PSMC6 , and PSMA3 , in autoimmune pathogenesis by analyzing associations between single nucleotide polymorphisms and systemic rheumatic diseases with a different autoimmune component: juvenile idiopathic arthritis (JIA), the juvenile form of systemic lupus erythematosus, and Kawasaki's disease (KD). Our results showed that the PSMA6 (rs1048990) polymorphism can be a risk factor for JIA (false discovery rate q ≤ 0.090), while PSMA3 (rs2348071) has a tendency to be nonspecific and is shared with JIA and other autoimmune diseases, including KD, an illness with very low autoimmune activity and high autoinflammation.

Alternating hemiplegia of childhood (AHC) is a rare autosomal dominant neurodevelopmental disorder with mutation on ATP1A3 gene. Delay in diagnosis and inappropriate diagnosis are common. In this article, we described four genetically confirmed AHC patients to provide an improved understanding of the disorder. First symptom in two patients was seizures and in other two patients was abnormal eye deviation. All had onset of plegic attacks within the first 18 months of their life. Tone abnormalities and movement disorders were present in all patients. Electroencephalogram was abnormal in two patients and all had normal magnetic resonance imaging of the brain. Response to treatment of plegic attacks was poor and also epilepsy was drug resistant. All cases had significant development delay and disability as of last follow-up. Although there is no effective treatment so far, early diagnosis is required to avoid unnecessary treatment.