A newborn male with Myhre syndrome, hearing loss, and complete syndactyly of fingers 3–4

Abstract Background Myhre syndrome is a rare multisystem genetic disorder that is caused by de novo heterozygous gain‐of‐function variants in SMAD4. Patients with Myhre syndrome exhibit several phenotypes at different ages such as small size, autism, developmental delay, left‐sided heart defects, and hearing loss and often have a characteristic facial appearance. The early clinical diagnosis of Myhre syndrome remains a major challenge, particularly in the first year of life. Methods A Chinese male infant with syndactyly of fingers, hypertelorism, short palpebral fissures, and short philtrum was enrolled into the ENT department of the Chinese PLA General Hospital. Whole exome sequencing analysis was used to detect the disease‐causing variant. A literature review of Myhre syndrome was also performed. Results A recurrent de novo missense variant c.1498A > G p.I500V(p. Ile500Val) in SMAD4 was detected confirming the clinical diagnosis of Myhre syndrome at the age of 38 days. The infant appears to be the youngest reported case of Myhre syndrome. At 23‐month follow‐up, the affected infant has dysmorphic facial features, growth retardation, and previously undescribed complete syndactyly. Review the literatures noted several common features in Myhre syndrome patients including hearing loss (72.7%), characteristic facial features (26.0%–54.5%), finger and toe abnormalities (3.9%–48.1%), short stature (45.5%), and respiratory (30.0%) and cardiovascular problems (65.0%). Conclusions Clinicians should have a low threshold to perform genetic testing on patients with features suggesting Myhre syndrome even in the first year of life. Although some individuals with Myhre syndrome have normal hearing, early onset or progressive hearing loss usually occur in one or both ears in most patients, with remarkable phenotypic heterogeneity. Syndactyly may be minor such as typical 2–3 toe involvement, or more complicated as was observed in our patient.