A child with Myhre syndrome presenting with corectopia and tetralogy of Fallot

Abstract

Myhre syndrome is a rare autosomal dominant disorder caused by a narrow spectrum of missense mutations in the SMAD4 gene. Typical features of this disorder are distinctive facial appearance, deafness, intellectual disability, cardiovascular abnormalities, short stature, short hands and feet, compact build, joint stiffness, and skeletal anomalies. The clinical features generally appear during childhood and become more evident in older patients. Therefore, the diagnosis of this syndrome in the first years of life is challenging. We report a 2‐year‐old girl diagnosed with Myhre syndrome by whole exome sequencing (WES) that revealed the recurrent p.Ile500Val mutation in the SMAD4 gene. Our patient presented with growth deficiency, dysmorphic features, tetralogy of Fallot, and corectopia (also known as ectopia pupillae). The girl we described is the youngest patient with Myhre syndrome. Moreover, corectopia and tetralogy of Fallot have not been previously reported in this disorder.

A pilot clinical trial with losartan in Myhre syndrome

“…Three female and one male individuals with MS were evaluated [(average age: 23.8 ± 17 years (range 3.8–41.3 years)] (Table 1). S1, S2, and S3 were previously reported (Alagia et al, 2018; Caputo et al, 2012; Titomanlio et al, 2001). All subjects carried the same recurrent pathogenic SMAD4 sequence variant (NM_005359.5: c.1498A>G, p.Ile500Val) and presented with typical facial dysmorphisms, cardiac abnormalities, and intellectual disability (Table 1).…”

“…Early diagnosis of MS by high‐throughput targeted, exome or genome sequencing is becoming increasingly more common (Alagia et al, 2018), thus offering the opportunity for surveillance of long‐term and life‐threatening disease complications. Moreover, there is a strong need to gain knowledge on the natural history of MS and to identify endpoints that can be evaluated to establish the efficacy of novel therapies.…”

Myhre syndrome: A first familial recurrence and broadening of the phenotypic spectrum

“…Based on previously reported ophthalmological findings in Myhre syndrome, we assume that the patient might instead have suffered from bilateral congenital cataract instead. (Alagia et al, 2018) In both probands, the diagnosis was delayed beyond the fourth life decade and eventually revealed with ES. This illustrates the difficulty of correctly and timely diagnosing patients with Myhre syndrome.…”

“…TOF has only been described once before in Myhre syndrome. (Alagia et al, ) Both the mother and her son present posttraumatic progressive proliferative fibrotic complications, respectively laryngotracheal stenosis and a persistent flexion contracture of the hip. The second proband presented with visual impairment following lensectomy in childhood, short stature, and stiff skin.…”

“…Based on previously reported ophthalmological findings in Myhre syndrome, we assume that the patient might instead have suffered from bilateral congenital cataract instead. (Alagia et al, )…”