Split Hand/Foot Malformation Associated with 7q21.3 Microdeletion: A Case Report

Abstract

Split hand/foot malformation (SHFM) or ectrodactyly is a rare genetic condition affecting limb development. SHFM shows clinical and genetic heterogeneity. It can present as an isolated form or in combination with additional anomalies affecting the long bones (nonsyndromic form) or other organ systems including the craniofacial, genitourinary and ectodermal structures (syndromic ectrodactyly). This study reports a girl with SHFM who also exhibited developmental delay, mild dysmorphic facial features and sensorineural hearing loss. High-resolution banding analysis indicated an interstitial deletion within the 7q21 band. FISH using locus-specific BAC probes confirmed the microdeletion of 7q21.3. Chromosomal microarray analysis also revealed a microdeletion of 1.856 Mb in 7q21.3. However, a larger 8.44-Mb deletion involving bands 7q21.11q21.2 was observed, and the breakpoints were refined. The phenotype and the candidate genes underlying the pathogenesis of this disorder are discussed.

Role of late amniocentesis in the era of modern genomic technologies

“…Nine pathogenic or likely pathogenic CNVs (9/303, 3%) were identified using CMA, of which only one could have been identified using traditional karyotyping (a deletion of 10 Mbp on chr11q24.2q25). The other eight abnormal CMA results (8/9, 89%) could not have been identified using traditional chromosomal analysis (Table ).…”

“…For example, a fetus presenting with gastroschisis had a de‐novo chr1q41‐q42 microdeletion of 5.5 Mbp compatible with Fryns syndrome, which includes gastroschisis. In another case, a fetus with limb malformations was found to have a microdeletion of 1900 kbp on chr7q21.3, flanking the SHFM1 (split hand/foot malformation 1) gene, which is associated with this phenotype.…”

“…All fetuses diagnosed with trisomy 21 or 18 had malformations associated with these aneuploidies as the indication for amniocentesis. Nine pathogenic or likely pathogenic CNVs (9/303, 3% [25][26][27][28][29][30][31][32] ) were identified using CMA, of which only one could have been identified using traditional karyotyping (a deletion of 10 Mbp on chr11q24.2q25 30 ). The other eight abnormal CMA results (8/9, 89%) could not have been identified using traditional chromosomal analysis (Table 4).…”

“…Six couples decided to terminate the pregnancy despite normal CMA results (6/271, 2.2%), based on diagnosis of worsening sonographic findings, specifically cardiovascular and brain malformations, and in one instance because of fetal CMV infection ( Table 5). Median gestational age at pregnancy termination was 32 (range, [25][26][27][28][29][30][31][32][33][34][35][36][37] weeks. Three of the seven pregnancies with trisomy 21 were continued, of which one ended in IUFD.…”

Gene expression patterns associated with fin shape differ between two lamprologine cichlids

“…This relationship appears, however, to be different in N. brichardi , where expression levels of sema3d and cx43 were significantly negatively correlated. In humans, mutations in cx43 and sema3d are associated with defects in finger growth (brachydactyly, (Kjaer et al, 2004; Jamsheer et al, 2014); ectrodactyly, (Sivasankaran et al, 2015), which may indicate that cx43 and sema3d act in skeletal growth across much of the vertebrate tree.…”