Diagnostic Criteria

Suggestive Findings Emanuel syndrome should be suspected in individuals with the following clinical features: • Severe intellectual disability • Microcephaly • Failure to thrive • Preauricular tag or pit • Ear anomalies • Cleft or high-arched palate • Micrognathia • Kidney abnormalities • Congenital heart defects • Genital abnormalities in males Establishing the Diagnosis The diagnosis of Emanuel syndrome is established in a proband by detection of a duplication of 22q10-22q11 and duplication of 11q23-qter on a supernumerary derivative chromosome 22 [der(22)] . Individuals with Emanuel syndrome have the following karyotypes: • Most commonly: • 47,XX,+der(22)t(11;22)(q23;q11) in females • 47,XY,+der(22)t(11;22)(q23;q11) in males • Rarely: a balanced (11;22) translocation as well as the supernumerary derivative chromosome. shows a karyotype of a balanced t(11;22) carrier. Genomic testing methods that determine the copy number of sequences can include karyotype, chromosomal microarray (CMA), or targeted duplication analysis by fluorescence in situ hybridization (FISH). Option 1 Karyotype. The supernumerary der(22) chromosome can be identified by routine G-band analysis at the 500-550 band level. • Parental karyotypes should be performed next to determine whether one parent is a carrier of the balanced translocation, t(11;22). • In the rare instance in which one of the parents is not a balanced translocation carrier, targeted duplication analysis (e.g., FISH) or CMA should be performed in the proband to identify the supernumerary chromosome in the karyotype as being derived from chromosomes 11 and 22. Option 2 CMA using oligonucleotide arrays or SNP genotyping arrays can detect the duplication of proximal 22q and distal 11q. • A limited karyotype should be pursued next to confirm that the duplications are due to a supernumerary chromosome; OR • FISH probe for 22q can determine that the extra chromosome is partially derived from chromosome 22 and a FISH probe for the 11q telomere can confirm that the translocation is between 11q and 22q. Note: Chromosomal microarray cannot currently detect balanced translocations, in which there is no net gain or loss of genetic material. Table 1. Molecular Genetic Testing Used in Emanuel Syndrome

Management Guidelines

Evaluations Following Initial Diagnosis

No current guidelines to evaluate the clinical manifestations that contribute to morbidity and mortality have been published. The following measures based on the literature and the authors' experience are recommended (if they have not already been completed) to establish the extent of disease and needs in an individual diagnosed with Emanuel syndrome:

Surveillance Guidelines

The following are appropriate:

• Follow up as needed based on the extent of systemic involvement in the affected individual

• Regular assessment of developmental progress to guide therapeutic interventions and educational modalities

• Periodic reevaluation by a clinical geneticist to apprise the family of new developments and/or recommendations