X-linked frontometaphyseal dysplasia 1

Abstract

X-linked filaminopathies are a diverse group of orphan diseases caused by mutations in the FLNA gene which encodes the cytoskeletal actin-binding protein filamin A. Pathogenic variants in this gene cause a wide range of genetic syndromes with signs of organ and tissue damage — skeletal dysplasia, cardiovascular and renal abnormalities. One of a group X-linked filaminopathies is frontometaphyseal dysplasia 1 (OMIM 305620). A clinical case of a 15-year-old boy with congenital anomalies of the kidney and urinary tract: posterior urethral valves, bilateral megaureter, neurogenic bladder was presented. In addition, the patient had congenital heart disease: atrial septal defect, valvular pulmonary artery stenosis and secondary chronic cicatricial-granular stenosis of the larynx. Phenotypic deviations were manifested by skeletal abnormalities that included facial dysmorphism — prominent brow ridges, wide bridge of the nose, orbital hypertelorism, small pointed chin; high-degree scoliosis; valgus deformity of the lower extremities; contractures of various joints. The child was short stature and had multiple congenital developmental features. New-generation whole-exome sequencing (Illumina, NextSeq 550) made it possible to detect a non-synonymous hemizygous variant of the FLNA gene: c.3557G>A (p.S1186L, rs137853312). The identified mutation was confirmed by Sanger sequencing. Genetic testing of the parents was carried out and the c.3557G>A hemizygous mutation was found in the patient’s mother. The use of NGS makes it possible to identify rare hereditary syndromes and make an accurate diagnosis, which is very important for choosing the right management of patient.