RESUMEN
OBJECTIVES: Hypochondroplasia (HCH) is characterized by disproportionate short stature and regarded as a milder form of achondroplasia (ACH), which is another skeletal dysplasia, both caused by variants in fibroblast growth factor receptor 3 (FGFR3) gene. HCH diagnosis is based on the clinical features and skeletal survey findings. The most common FGFR3 variant in HCH affects the codon 540, leading to substitution of asparagine with lysine in about 70% of patients. CASE PRESENTATION: Herein, we described the clinical and radiographical manifestations of HCH in affected members of a Turkish family with very rare Asn540Thr (c.1619A>C) variant within hot spot of the gene for this condition. CONCLUSIONS: This is a very rarely reported variant in the literature and this report is the first case with this variant in Turkish population. The report also presents the phenotypic variability within a family with the same variant, which is inherent to HCH.
Asunto(s)
Acondroplasia , Deformidades Congénitas de las Extremidades , Lordosis , Acondroplasia/diagnóstico por imagen , Acondroplasia/genética , Huesos/anomalías , Enanismo , Humanos , Deformidades Congénitas de las Extremidades/diagnóstico por imagen , Deformidades Congénitas de las Extremidades/genética , Lordosis/diagnóstico por imagen , Lordosis/genética , Mutación , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genéticaRESUMEN
Somatic and germline PI3K-AKT-mTOR pathway pathogenic variants are involved in several segmental overgrowth phenotypes such as the PIK3CA-related overgrowth spectrum (PROS), Proteus syndrome, and PTEN hamartoma tumor syndrome. In this study, we describe five patients with PROS. We identified by high-throughput sequencing four different somatic PIK3CA pathogenic variants in five individuals. The Glu726Lys variant, which was previously reported in megalencephaly-capillary malformation-polymicrogyria (MCAP) syndrome, was identified in two patients with unclassified PROS. The Cys420Arg substitution, which was previously reported in CLOVES, was found in a patient with fibroadipose hyperplasia. Additionally, relatively rare pathogenic variants, His1047Tyr and Tyr1021Cys, were detected in two patients with MCAP. Therefore, we suggest performing deep sequencing of PIK3CA in all patients with suspected PROS, instead of targeted polymerase chain reaction for hotspot pathogenic variants.
