First female Korean child with Coffin-Lowry syndrome: a novel variant in RPS6KA3 diagnosed by exome sequencing and a literature review

Coffin-Lowry syndrome (CLS, OMIM # 303600) is a rare X-linked disorder caused by mutations in RPS6KA3. CLS is characterized by facial dysmorphism, digit abnormalities, developmental delays, growth retardation, and progressive skeletal changes in male patients. Females with CLS are variably affected, complicating diagnosis. Here, we describe the clinical and molecular findings in a female Korean child with CLS and review the associated literature. A 5-year-old girl presented with short stature and developmental delays. She had a coarse facial appearance characterized by a prominent forehead, hypertelorism, thick lips, and hypodontia. She also had puffy tapering fingers and pectus excavatum. We performed exome sequencing and identified a novel, likely pathogenic, heterozygous variant, c.326_338delinsCTCGAGAC (p.Val109Alafs*10), in RPS6KA3 (NM_004586.2). This is the first Korean female genetically diagnosed with CLS. In contrast to the delayed bone age reported in previous studies, our patient showed advanced bone age and central precocious puberty. CLS should be considered as a differential diagnosis of short stature, tapering fingers, and developmental delay. We suggest that molecular techniques can be a useful tool for diagnosis of rare disorders such as CLS because such conditions are not simple, and the associated spectrum of phenotypes can vary.

Excellent treatment outcomes in children younger than 18 months with stage 4 MYCN nonamplified neuroblastoma / 소아과

PURPOSE: Although the prognosis is generally good in patients with intermediate-risk neuroblastoma, no consensus has been reached on the ideal treatment regimen. This study analyzed treatment outcomes and toxicities in patients younger than 18 months with stage 4 MYCN nonamplified neuroblastoma. METHODS: We retrospectively analyzed 20 patients younger than 18 months newly diagnosed with stage 4 MYCN nonamplified neuroblastoma between January 2009 and December 2015. Patients received 9 cycles of chemotherapy and surgery, with or without local radiotherapy, followed by 12 cycles of differentiation therapy with 13-cis-retinoic acid. Chemotherapy consisted of alternating cycles of cisplatin, etoposide, doxorubicin, and cyclophosphamide (CEDC) and ifosfamide, carboplatin, and etoposide (ICE) regimens. RESULTS: The most common primary tumor site was the abdomen (85%), and the most common metastatic sites were the lymph nodes (65%), followed by the bones (60%), liver (55%), skin (45%), and bone marrow (25%). At the end of induction therapy, 14 patients (70%) achieved complete response, with 1 achieving very good partial response, 4 achieving partial response, and 1 showing mixed response. Nine patients (45%) received local radiotherapy. At a median follow-up of 47 months (range, 17–91 months), none of these patients experienced relapse, progression, or secondary malignancy, or died. Three years after chemotherapy completion, none of the patients had experienced grade ≥3 late adverse effects. CONCLUSION: Patients younger than 18 months with stage 4 MYCN nonamplified neuroblastoma showed excellent outcomes, without significant late adverse effects, when treated with alternating cycles of CEDC and ICE, followed by surgery and differentiation therapy.