Emanuel syndrome: A rare disorder that is often confused with Kabuki syndrome

Dear Sir,

I read with great interest the recent article by Topcu et al.[1] Interestingly, Kabuki syndrome is often confused with another rare syndrome-“Emanuel syndrome” (ES).

Overall, ES is a rare clinical entity characterized by microcephaly and psychomotor delay in males. ES occurs secondary to a supernumerary derivative chromosome 22 resulting in chromosomal imbalance.[2] Characteristically, there is 3:1 abnormal segregation of a parental balanced translocation between chromosomes 11 and 22 resulting in a spectrum of different abnormalities. Interestingly, patients with ES may also develop concurrent immunological abnormalities. For instance, Tovo et al. have recently reported decreased immunoglobulin levels in affected individuals.[3] In nearly 90% of affected patients, the mother is the carrier of the translocation.

Ear pits are the most common congenital abnormality seen in affected patients and may be seen in almost 76% of all patients. Angular mouth pits may also be seen. Glaser et al. have also reported the bilateral absence of the ear canals in some patients with ES.[4] In fact, nearly 15% of patients with ES develop severe hearing loss. Strabismus (33%), myopia (38%), and/or ptosis (8%) are other commonly seen ophthalmological abnormalities. Rare conjunctival lesions such as lipodermoid as well as other ocular abnormalities such as Duane's anomaly have also been reported.[5]53% of the patients also exhibit a cleft palate while 60% also exhibit micrognathia. In addition, patients may have a bifid uvula. Patients have a characteristic facial dysmorphism comprised of a prominent long philtrum, a flat nasal bridge, large low-set ears, and down-slanting palpebrae with epicanthal folds. Facial asymmetry is common.[6] Psychomotor delay is seen in all patients afflicted with ES. For instance, affected children first exhibit a smile at a mean age of 7 months. Similarly, most affected patients with ES first start crawling around a mean age of thirty four months. In addition, anxiety has been noted in 16% of affected individuals.

Gremeau et al. have also reported congenital diaphragmatic hernia in ES.[7] Similarly, inguinal hernias are seen in 14% of patients. Cardiac anomalies are also seen in almost 62% of all affected patients. Commonly encountered defects include tetralogy of Fallot, persistent left superior vena cava, and “patent ductus arteriosus.” Defects such as ASD (45%) and VSD (13%) are also common. Patients may also develop intra-abdominal anatomical anomalies. For instance, Fenerci et al. have recently reported pancreatic hypoplasia as well as agenesis of the left hepatic lobe in ES.[8] Nearly 54% of affected children also develop gastro-esophageal reflux. Hirschsprung disease and biliary atresia have also been reported in some patients with ES. In addition, 19% of affected patients develop renal abnormalities. In addition, cryptorchidism is seen in 46% of patients while recurrent urinary tract infections are seen in 18% of affected individuals.

Neurological abnormalities are also frequently seen in patients with ES. For instance, nearly 48% of affected patients develop seizures.[9] On the other hand, hypotonia is seen in 65% of cases. Medne et al. in a recent study have reported that microcephaly is a universal finding in ES and is seen in 100% of all affected males.[10] In addition, hydrocephalus may develop in 11% of affected patients. In addition, Dandy Walker malformation develops in 8% of patients while hypoplasia of the corpus callosum is seen in 19% of cases.

A number of skeletal abnormalities may also develop in ES. For instance, nearly 47% of patients develop dislocation of the hip joints while joint contractures develop in 15% of patients with ES. Zaki et al. have recently also reported hyper-extensibility of the joints of the hands and arachnodactyly in some patients with ES.[11] Bilateral talipes may also be seen. In addition, scoliosis and kyphosis affect nearly 1/3^rd of the patients. In addition, affected patients may have extra finger creases.

Failure to thrive is seen in as many as 63% of affected children.[12] Patients are especially prone to recurrent infections especially recurrent otitis media. Similarly, recurrent pneumonia develops in nearly 47% of affected patients.[13] Nearly 1/5^th of affected patients end up requiring a G tube.[14]

As is obvious from the above discussion, ES may mimic Kabuki syndrome. Identification of the above features may help in early diagnosis of ES.