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Penttinen type of premature aging syndrome is an extremely rare progeroid disorder, caused by activating variants in the receptor tyrosine kinase domain of the PDGFRB gene. Only eight individuals have been previously reported worldwide, with a consistent phenotype of prematurely aged appearance, lipoatrophy, hypertrophic skin lesions, proptosis, malar hypoplasia, and marked acro-osteolysis. We report the first patient of Penttinen syndrome from India, with novel radiographic findings of terminal phalangeal tufting, thereby expanding the phenotypic spectrum of Penttinen syndrome.

Spondylo-meta-epiphyseal dysplasia, short limb-abnormal calcification type is a rare autosomal recessive disorder causing severe disproportionate short stature along with typical radiological features. We report an adult male patient with typical features and a novel homozygous nonsense mutation c.2422C > T (p.Gln808Ter) in DDR2. This is the first report of the disease from India.

Introduction Nonimmune hydrops fetalis (NIHF) has varied etiology. We assessed the etiological spectrum and evaluated the utility of fetal whole exome sequencing (fWES) for the diagnosis of NIHF. Methods In this prospective cohort study, we evaluated antenatally diagnosed fetuses with NIHF between July 2018 and December 2019 according to the routine diagnostic algorithm. Fetuses that remained undiagnosed after routine NIHF workup were subjected to fetal chromosomal microarray and/or WES. Pregnancies were followed up for clinical outcomes. Results Of the 45 fetuses, consanguinity and recurrent hydrops fetalis were observed in 13.3% (6/45) and 28.8% (13/45), respectively. Overall, an etiological diagnosis was possible in 75.5% (34/45) of fetuses, while the cause remained unknown in 24.4% (11/45). A genetic etiology was identified in 46.6% (21/45): aneuploidy and monogenic disorders in 28.8% (13/45) and 17.8% (8/45), respectively. fWES on 19 fetuses detected disease-causing variants in 42.1% (8/19). Nine novel variants were detected in RAPSN, ASCC1, NEB, PKD1L1, GUSB, and PIEZO1. Only 8.8% (4/45) of the cohort survived without morbidity. Conclusions This study describes the etiological spectrum and the disease-causing variants in an Indian cohort of hydropic fetuses.

Mevalonate kinase deficiency (MKD) is a rare autosomal recessive autoinflammatory disease caused by mutations in MVK. We report two siblings with MKD, presenting with recurrent febrile illnesses, detected to have compound heterozygous variants in MVK. MKD mimics common pediatric conditions and should be considered as a differential diagnosis.

Ethylmalonic encephalopathy (EME) is a rare autosomal recessive inherited metabolic disease characterized by developmental delay, ecchymotic patches, and acrocyanosis with chronic diarrhea. We report a first case of EME from India who primarily presented with chronic diarrhea since early infancy and developmental delay. Mutation analysis of ETHE1 showed presence of a previously reported homozygous mutation in exon 4 confirming the diagnosis. She was started on riboflavin, CoQ, carnitine, metronidazole and N-acetyl cysteine with improvement in diarrhea but neurological features continue to progress. Prenatal diagnosis was performed in the next pregnancy. Though, EME is a devastating inherited metabolic disorder with mortality usually in early infancy, here we have reported a case presented as late as at 4 years. A high index of suspicion followed by specific molecular diagnosis not only ends the diagnostic odyssey but also ensures prenatal diagnosis in the future pregnancies.

To report a phenotypic series of eight patients of Beckwith-Wiedemann Syndrome (BWS) with abnormalities of 11p15.5 region to highlight the spectrum of phenotypic manifestations. All the cases were evaluated using Methylation Specific Multiplex Ligation Dependent Probe Amplification (MS-MLPA) of 11p15.5 region to detect the abnormal methylation status of ICR1 (H19DR) and ICR2 (KvDMR) regions. The median age at diagnosis was 5.7 mo (range 1.5–13 mo) with female preponderance. Macroglossia, ear creases and abdominal wall defects were the major features. Hypomethylation at ICR2 and hypermethylation at ICR1 was observed in 6/8 and 2/8 patients respectively. No specific genotype and phenotype correlation was observed. This report highlights the major clinical features of BWS that should prompt pediatricians to offer genetic testing to evaluate the epigenetic abnormalities using MS-MLPA, as it not only helps in appropriate counseling but also provides further guidance about the tumor risk surveillance.