Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare skeletal disorder characterized by aggressive osteolysis associated with progressive nephropathy. The early clinical presentation can mimic polyarticular juvenile idiopathic arthritis. Since 2012, MAFB mutations have been discovered in all MCTO patients. Therefore, the early diagnosis can be made based on genetic confirmation. We report the clinical manifestation of mineral bone disease and the molecular genetic study of a Thai female adolescent with MCTO. She presented with end-stage renal disease, bilateral wrist and ankle joint deformities, and subtle facial dysmorphic features. We identified a heterozygous missense MAFB mutation at nucleotide 197 from C to G (NM_005461.4; c.197C>G), predicting the change of amino acid at codon 66 from serine to cysteine (p.Ser66Cys), and the mutation was absent in the parents, indicating a de novo mutation. This report confirms the previous link between MAFB mutation and MCTO. Her unexplained hypercalcemia after a regular dose of calcium and active vitamin D supported an important role of MafB in the negative regulation of RANKL-mediated osteoclast differentiation. Therefore, we would encourage the physicians who take care of MCTO patients to closely monitor serum calcium level and perform a genetic study as a part of the management and investigation.

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Adams-Oliver syndrome (AOS), a rare inherited disorder, is characterized by scalp and terminal limb defects. Several genes associated with Notch pathway mutations have led to AOS. Here, we report a Thai male newborn presenting with aplasia cutis congenita and absence of a right pulmonary artery, which is suggestive of AOS. This was confirmed by the identification of a novel missense mutation in DLL4, a heterozygous one base pair change at nucleotide 82 (c.82G>C, p.Gly28Arg), which is in Nterminal domain. This is the first DLL4-related AOS case with arterial defect.

Clinical utility of genetic testing has rapidly increased in the past decade to identify the definitive diagnosis, etiology and specific management. The majority of patients receiving testing is children. There are several barriers for genetic tests in adult patients; barriers may arise from either patients or clinicians. Our study aims to realize the detection rate and the benefits of genetic tests in adults. We conducted a prospective study of 10 adult patients who were referred to a genetic clinic. Exome sequencing (ES) was pursued in all cases, and chromosomal microarray (CMA) was performed for 6 cases. Our result is impressive; six cases (60%) received likely pathogenic and pathogenic variants. Four definitive diagnosis cases with known pathogenic variants inKCNJ2,TGFBR1,SCN1AandFBN1, while another two cases revealed novel likely pathogenic and pathogenic variants inGNB1andDNAH9. Our study demonstrates the success in genetic diagnosis in adult patients, four cases with definitive, two cases with possible, and one case with partial diagnosis. The advantage of diagnosis is beyond obtaining the diagnosis itself, but also relieving any doubt for the patient regarding any previous questionable diagnosis, guide for management and recurrence risk in their children or family members. Therefore, this supports the value of genetic testing in adult patients.

The 22q11.2 deletion syndrome (22q11.2 DS) is the most common microdeletion syndrome with a wide variety of clinical features. However, as there are no clinical criteria for diagnosis, confirmation is solely done by genetic tests if clinicians recognize the syndrome. Therefore, we aimed to identify clinical features that may help clinicians recognize 22q11.2 DS. Participants with at least two anomalies were enrolled, complete patient history and physical examinations were performed, then multiplex ligation-dependent probe amplification (MLPA) analysis for 22q11.2 DS was utilized. We identified 11/48 (23%) cases with 22q11.2 DS. Palatal anomalies, hypocalcemia, and ≥3 affected body systems were highly significant presentations in the 22q11.2 DS group versus the group without deletion (p < 0.05). Therefore, a comprehensive physical examination is crucial at identifying any subtle features which may lead to testing and a definite diagnosis.