دورية أكاديمية
Short Bones, Renal Stones, and Diagnostic Moans: Hypercalcemia in a Girl Found to Have Coffin-Lowry Syndrome.
| العنوان: | Short Bones, Renal Stones, and Diagnostic Moans: Hypercalcemia in a Girl Found to Have Coffin-Lowry Syndrome. |
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| المؤلفون: | Tise CG; Stanford University, CA, USA., Matalon DR; Stanford University, CA, USA., Manning MA; Stanford University, CA, USA., Byers HM; Stanford University, CA, USA., Grover M; Stanford University, CA, USA. |
| المصدر: | Journal of investigative medicine high impact case reports [J Investig Med High Impact Case Rep] 2022 Jan-Dec; Vol. 10, pp. 23247096221101844. |
| نوع المنشور: | Journal Article; Case Reports |
| اللغة: | English |
| بيانات الدورية: | Publisher: Sage on behalf of: American Federation for Medical Research Country of Publication: United States NLM ID: 101624758 Publication Model: Print Cited Medium: Internet ISSN: 2324-7096 (Electronic) Linking ISSN: 23247096 NLM ISO Abbreviation: J Investig Med High Impact Case Rep Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Thousand Oaks, CA] : Sage on behalf of: American Federation for Medical Research |
| مواضيع طبية MeSH: | Coffin-Lowry Syndrome*/genetics , Dwarfism* , Hypercalcemia*/etiology , Hypercalcemia*/genetics , Intellectual Disability*, Child, Preschool ; Female ; Humans ; Male ; Ribosomal Protein S6 Kinases, 90-kDa/genetics |
| مستخلص: | Pathogenic variants in RPS6KA3 are associated with Coffin-Lowry syndrome (CLS), an X-linked semidominant disorder characterized by intellectual disability, stimulus-induced drop attacks, distinctive facial features, progressive kyphoscoliosis, and digit anomalies in hemizygous males. Heterozygous females may also have features of CLS; however, there can be considerable phenotypic variation, often attributed to ratios of X-inactivation in various tissue types. Although skeletal anomalies and short stature are hallmarks of CLS, hypercalcemia has not been reported. Here we describe a 30-month-old girl with gross motor delays, short stature, dysmorphic features, bilateral duplicated renal collecting systems, and no family history of hypercalcemia who required multiple admissions for idiopathic hypercalcemia necessitating bisphosphonate infusions at 12.5 and 15 months of age. A maternally inherited likely-pathogenic variant in RPS6KA3 was identified by trio exome sequencing, consistent with the diagnosis of CLS in the proband and her mother. Maternal history was notable only for decreased height compared to first-degree relatives, bilateral genu valgum, and a bicornuate uterus; she was later found to also have a partially duplicated left renal collecting system. Subsequent X-inactivation studies in blood aligned with the phenotypic variation between mother and daughter. Although hypercalcemia is not a reported feature in CLS, there is evidence of interrupted osteoblast differentiation, providing a potential mechanism for hypercalcemia in this genetic condition. The hypercalcemia in this case may represent a severe presentation of an unrecognized clinical feature in CLS that resolves with age. This case further highlights the intrafamilial phenotypic variation of CLS among females, suggesting X-inactivation as the underlying mechanism, and demonstrates the value of exome sequencing in patients for whom a genetic disorder is highly suspected but not identified despite thorough evaluation. |
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| فهرسة مساهمة: | Keywords: endocrinology; genetic and molecular medicine; pediatrics |
| المشرفين على المادة: | EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 90-kDa) |
| تواريخ الأحداث: | Date Created: 20220531 Date Completed: 20220602 Latest Revision: 20231031 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC9160898 |
| DOI: | 10.1177/23247096221101844 |
| PMID: | 35638718 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2324-7096 |
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| DOI: | 10.1177/23247096221101844 |