Rare features in Feingold syndrome type 1.

Abstract

Feingold syndrome type 1 (FS1) (OMIM 164280) is an autosomal dominant condition due to heterozygous loss of function variants in MYCN gene or to 2p24 deletion encompassing MYCN gene. The core features of FS1 are digital anomalies, microcephaly, facial dysmorphism, short stature, esophageal/duodenal atresia, and mild learning disabilities. Additional features are reported in a minority of patients, such as cardiac and renal anomalies. Sensorineural deafness is reported in 7 % of the patients. Other features can be associated with classical features of FS1 in patients with 2p deletion including MYCN and other genes. Recently, absence of the flexor pollicis longus tendon has been reported as a new skeletal feature in a pedigree segregating a MYCN variant. Here, we reported on three patients having FS1 without gastrointestinal atresia and unusual features: laryngeal cleft, congenital deafness, agenesis of the corpus callosum, and radio ulnar-synostosis (RUS). After the extension of the genetic screening, RUS was considered as an independent condition linked to SMAD6 variant. Diagnosis of FS1 can be challenging when there are unusual features without digestive malformations drawing attention. In this situation, the diagnostic approach may be based on major criteria of FS1: i) brachymesophalangy of the 2^nd and 5^th fingers, brachydactyly of fingers and toes with or without 2/3 and/or 4/5 toe syndactylies, ii) microcephaly, and iii) radiographs of the feet to look for amesophalangy of toes. Extension of the genetic screening is required to eliminate the possibility of two independent conditions. In addition to the previous recommendations, we advocate for a set of recommendations for evaluation of FS1 patients following initial diagnosis: systematic search of deafness, verification of the flexion of the interphalangeal joints of the thumbs, laryngoscopy in case of stridor or swallowing disorders, and finally systematic cerebral MRI.