Nager syndrome

Disease summary: Nager syndrome is a rare syndrome that has an unknown prevalence. It shares some phenotypic features of Treacher-Collins syndrome. The literature describes sporadic cases (de novo mutation) as well as autosomal dominant or recessive and spontaneous inheritance patterns. It is caused by a genetic mutation in the SF3B4 gene (1q21.2), preventing the function of the SAP49 protein, which is important for bone and cartilage maturation. This results in an abnormal development of the 1st and 2nd brachial arches and limb buds. Clinical manifestations include: craniofacial malformations (malar hypoplasia, micrognathia, cleft palate, down-slanting palpebral fissures, absent eyelashes in the middle of the eyebrows, lower eyelid coloboma, external auditory defects, conductive hearing loss, choanal atresia) and pre- axial limb malformations predominately of the upper limb (hypoplastic/absent thumbs, clinodactyly or syndactyly, shortened or absent forearm, shortened humeral bone) and, less commonly, lower limb abnormalities. More rarely is an involvement of the heart (Fallot tetralogy, ventricular septal defect, atrial septal defect, patent ductus arteriosus), kidneys, genitalia and urinary tract. It is associated with normal cognitive function.