Growth hormone deficiency, aortic dilation, and neurocognitive issues in Feingold syndrome 2

Abstract

We report three patients with Feingold 2 syndrome with the novel features of growth hormone deficiency associated with adenohypophyseal compression, aortic dilation, phalangeal joint contractures, memory, and sleep problems in addition to the typical features of microcephaly, brachymesophalangy, toe syndactyly, short stature, and cardiac anomalies. Microdeletions of chromosome 13q that include the MIR17HG gene were found in all three. One of the patients was treated successfully with growth hormone. In addition to expanding the phenotype of Feingold 2 syndrome, we suggest management of patients with Feingold 2 syndrome include echocardiography at the time of diagnosis in all patients and consideration of evaluation for growth hormone deficiency in patients with short stature.

Proximal variants in CCND2 associated with microcephaly, short stature, and developmental delay: A case series and review of inverse brain growth phenotypes

“…Microdeletions of chromosome 13q that include the MIR17HG gene are associated with Feingold 2 syndrome, with features of microcephaly, brachymesophalangy, toe syndactyly, short stature, cardiac anomalies, growth hormone deficiency, aortic dilation, phalangeal joint contractures, memory, and sleep problems (de Pontual et al, 2011;Muriello et al, 2019). Recently, a de novo 13q31.3 microduplication encompassing MIR17HG was described in a female patient with developmental delay, skeletal and digital abnormalities, and tall stature and macrocephaly (Siavriene et al, 2020).…”

Feingold syndrome type 2 in a patient from China

“…Apart from six cases recorded in DECIPHER database, who have some clinical phenotype of FGLDS2. The total number of patients with FGLDS2 (summarized in Table 1) described in the literature was 16 (including the present case) (de Pontual et al, 2011;Firth et al, 2009;Ganjavi et al, 2014;Grote et al, 2015;Low et al, 2015;Muriello et al, 2019;Sharaidin et al, 2013;Sirchia et al, 2017;Tassano et al, 2013;Valdes-Miranda et al, 2014). Among these patients, the deletions range in size from 165 kb to 17.2 Mb in the area that includes MIR17HG (encoding miR-17 92 miRNA cluster) and 141 additional genes (arr[hg19] chr13:81,484,523-99,930,889) (Sharaidin et al, 2013;Wierenga et al, 2013).…”

“…It is classified into two types: Feingold syndrome type 1 (FGLDS1) is caused by pathogenic variants in or deletion of MYCN gene encoding N-myc located in 2p24.1 (Chen et al, 2012); Feingold syndrome type 2 (FGLDS2) is caused by partial deletion at chromosome 13q resulting in haploinsufficiency of MIR17HG (Sirchia et al, 2017). Heretofore, there have only been 15 diagnosed patients of FGLDS2 described in the literature and 6 cases with similar phenotypic features recorded in the DECIPHER database (Muriello et al, 2019).…”

Metacarpophalangeal pattern profile analysis for a 3‐month‐old infant with Feingold syndrome 2

“…Feingold syndrome (FGLDS), also known as microcephaly‐oculo‐digito‐esophageal‐duodenal syndrome, is an autosomal dominant disorder characterized by microcephaly, short palpebral fissures, limb malformations, and atresia of the esophagus and duodenum varying in combination. The limb anomalies include shortening of the middle phalanges, thumb hypoplasia, and toe syndactyly (Celli, van Bokhoven, & Brunner, 2003; Feingold, Hall, Lacassie, & Martinez‐Frias, 1997; Grote, Repnikova, & Amudhavalli, 2015; Muriello et al, 2019). Intellectual and developmental disabilities are sometimes seen.…”

“…Currently, very little is known about the clinical and radiological spectrum of FGLDS2 or MIR17HG haploinsufficiency. To date, the previous reports have addressed only 15 individuals with FGLDS2 (Muriello et al, 2019), and a few individuals with deletions encompassing MIR17HG have also been noted to show FGLDS2‐like skeletal features in the DECIPHER database (https://decipher.sanger.ac.uk/). Here, we report a Japanese boy with FGLDS2 due to a heterozygous 5.3 Mb deletion including MIR17HG .…”