Phenotypic delineation of Emanuel syndrome (supernumerary derivative 22 syndrome): Clinical features of 63 individuals

Abstract

Emanuel syndrome is characterized by multiple congenital anomalies and developmental disability. It is caused by the presence of a supernumerary derivative chromosome that contains material from chromosomes 11 and 22. The origin of this imbalance is 3:1 malsegregation of a parental balanced translocation between chromosomes 11 and 22, which is the most common recurrent reciprocal translocation in humans. Little has been published on the clinical features of this syndrome since the 1980s and information on natural history is limited. We designed a questionnaire to collect information from families recruited through an international online support group, Chromosome 22 Central. Data gathered include information on congenital anomalies, medical and surgical history, developmental and behavioral issues, and current abilities. We received information on 63 individuals with Emanuel syndrome, ranging in age from newborn to adulthood. As previously recognized, congenital anomalies were common, the most frequent being ear pits (76%), micrognathia (60%), heart malformations (57%), and cleft palate (54%). Our data suggest that vision and hearing impairment, seizures, failure to thrive and recurrent infections, particularly otitis media, are common in this syndrome. Psychomotor development is uniformly delayed, however the majority of individuals (over 70%) eventually learn to walk with support. Language development and ability for self-care are also very impaired. This study provides new information on the clinical spectrum and natural history of Emanuel syndrome for families and physicians caring for these individuals.

Fig. 1

Individuals with Emanuel syndrome at various ages: newborn (a and b), preschool age (c to f), school age (g to n) and adolescent (o to s). The common dysmorphic features are demonstrated, including micrognathia (most obvious in infancy and preschool age), hooded eyelids, deep-set eyes, upslanting palpebral fissures, low-hanging columnella, and long philtrum. Some individuals have facial asymmetry and/or unilateral ptosis (for example, Patients g and k).

Fig. 2

Six individuals with Emanuel syndrome, demonstrating evolution of facial features with age. Approximate ages are: a) 12 months and 13 years; b) 8 months and 15 years; c) 24 months and 8 years; d and e) 4 years and 28 years; f) 30 months and 20 years. Patients d and e are siblings. Note that, as expected, there is facial elongation and growth of the mandible with age. Features remain fine, without significant coarsening.