Clinical Description
Well over 400 individuals with supernumerary der(22) have been identified by support groups and by report. Significant mortality is associated with life-threatening congenital malformations such as congenital heart defects, diaphragmatic hernia, or renal insufficiency. The highest mortality rate is in the first months of life. With improved palliative care and time, survival chances improve and survival into adulthood has been documented.
Affected children are usually identified in the newborn period as the offspring of balanced (11;22) translocation carriers.
Growth. Most individuals have pre- and postnatal growth deficiency.
Craniofacial. Observed dysmorphic features include microbrachycephaly, prominent forehead, epicanthus, downslanted palpebral fissures, wide and depressed nasal bridge, long and deep philtrum, and microretrognathia (see ).
Four individuals with Emanuel syndrome. Note the round face, deeply set, round eyes, and prominent forehead in children A (age ~6 months) and B (age 3 years). Note the coarsening of facial features over time in individual D; photos are taken at age one (more...)
The external ear auricle is typically malformed and preauricular ear pits and/or tags are characteristic. Severe microtia with atresia of the external auditory canal and deafness have been reported. Hearing loss is uncommon, but milder forms may be underestimated because of the difficulties associated with accurate hearing evaluation in individuals with severe developmental delay.
Cleft palate is seen in approximately 50% of affected individuals. Angular mouth pits or clefts, cleft maxilla, laryngomalacia, and branchial sinuses have been reported. Bifid uvula is also associated.
Cardiac. Congenital heart defects, seen in approximately 60% of individuals with Emanuel syndrome, contribute to morbidity and mortality. Heart defects include atrial septal defect, ventricular septal defect, tetralogy of Fallot, truncus arteriosus, tricuspid atresia, coarctation of the aorta, aberrant subclavian artery, persistent left superior vena cava, and patent ductus arteriosus.
Genitourinary. Renal malformations, seen in approximately 30% of affected individuals, range from complete renal agenesis to various degrees of renal hypoplasia. Males often have cryptorchidism, small scrotum, and micropenis. Uterine malformations can occasionally be observed in females.
Gastrointestinal.
Diaphragmatic hernia and hypoplasia or eventration of the diaphragm have been observed.
Anal atresia with or without fistula is seen in about 20% of affected individuals. Anal stenosis without complete atresia is observed as well.
Inguinal hernias are uncommon but well documented.
Biliary atresia, Hirschsprung disease, abnormal liver lobation, extrahepatic biliary ducts, absent gallbladder, and polysplenia have been observed occasionally.
Poor weight gain is common. While specific feeding problems are often not described, gastroesophageal reflux and difficulties with suck and swallow are common.
Musculoskeletal. All affected individuals have significant centrally based hypotonia.
Curvature of the spine is most likely a secondary complication of severe hypotonia and resulting motor delays.
Sacral dimple is common.
Congenital hip dislocation or subluxation is common.
Arachnodactyly and tapering fingers are characteristic.
Clubfoot and joint contractures can be congenital or develop later in life.
Other, less frequently observed skeletal malformations include 13 pairs of ribs, hypoplastic clavicles, cubitus valgus, radioulnar synostosis, and 4-5 syndactyly of the toes. Lumbar myelomeningocele has been reported once.
Delayed bone age is mentioned in a few reports.
Eyes. Most persons with Emanuel syndrome have normal vision. Although uncommon, eye abnormalities have included strabismus and myopia. Ptosis and degenerative retinal changes are less common.
CNS. Microcephaly is present in all affected individuals.
The incidence of structural brain abnormalities is not known as brain imaging is not required to establish the diagnosis. Reported malformations have included Dandy-Walker malformation, agenesis of the corpus callosum, arrhinencephaly, and absent olfactory bulbs and tracts.
Seizures are reported in a few affected individuals and abnormal EEGs without clinical seizures in another small subset.
Development. All children with Emanuel syndrome have severe developmental delays. Adults function in the spectrum of severe-to-profound intellectual disability. Most individuals can sit unsupported. Walking is often difficult because of poor motor coordination; only a small number learn to walk. Speech and language development is significantly delayed. Receptive language is better than expressive language and some individuals are able to use single words to communicate.
Other findings include congenital immunoglobulin deficiency, thymic-dependent immunodeficiency, and dysplastic teeth.
