A case with Emanuel syndrome: extra derivative 22 chromosome inherited from the mother

Emanuel syndrome (ES) is an unbalanced translocation syndrome, usually arising through a 3:1 meiosis I malsegregation during gametogenesis in a phenotypically balanced translocation normal carrier. While the true mortality rate in Emanuel syndrome is unknown, long-term survival is possible [1]. Emanuel syndrome is also referred to as derivative 22 syndrome, derivative 11;22 syndrome, partial trisomy 11;22, or supernumerary der(22)t(11;22) syndrome [2]. In this partial duplication, 11(q23-qter) and 22(pter-q11) complex, congenital diaphragmatic hernia has been observed [3]. There is growth retardation, mental retardation (severe), cardiovascular malformation, craniofacial anomalies (including pre auricular tags or sinuses, micrognathia, ear anomalies, cleft or high-arched palate), microcephaly, kidney abnormalities and genital abnormalities in males [1,4].

We report a 3-year-old boy with the t(11;22) (q23;q11) chromosome, transmitted in an unbalanced fashion from his mother. It was her first pregnancy; the patient’s mother and grandmother have no history of the disease (Figure 1). The prenatal period of the infant was uneventful. The infant was delivered at full-term by vaginal delivery. His birth weight was 3.25 kg, length 52 cm. At birth, he was found to have a cleft palate, micrognathia, undescended testis, in guinal hernia, and surgery was performed to correct these anomalies (Figure 2).

He is now 3 years old and echocardiography revealed a secundum atrial septal defect of about 10 mm. He also has central nervous system (CNS) and skeletal anomalies, mental retardation, hypotonia, white matter abnormalities, cerebral atrophy, scoliosis, kyphosis and glaucoma. On hearing assessment, he has bilateral hearing loss. He has gallstones and feeding problems. He was admitted to our hospital repeatedly due to respiratory infections and recurrent ear infections. His head circumference is 48 cm and he has a short neck with low posterior hairline. Magnetic resonance imaging (MRI) showed lateral ventricles are enlarged to approximately 22mm (Figure 3). He has several developmental delays; he is not independently ambulatory and language is significantly impaired.

Using his peripheral blood, karyotyping was performed to define his multiple congenital anomalies, revealing the chromosomal abnormality 47, XY,+der(22)t(11;22) (q23.3; q11.2) (Figure 4). To ascertain the origin and trait of this supernumerary marker chromosome [der(22) t(11; 22)(q23.3;q11.2)] karyotyping of his parents was performed. The mother was found to be a balanced carrier: 46, XX, t(11;22)(q23.3;q11.2) (Figure 5). We used fluorescent in situ hybridization (FISH) probes for the 22q11.2 and 22q13.3 deletions and identified the supernumerary chromosome der(22)t(11;22) (Figure 6)/maternal t(11;22) (q23.3;q11.2) (Figure 7). We used Aquarius® Microdeletion Syndrome probes, DiGeorge/ VCFS TUPLE 1 and 22q13.3 Deletion Syndrome ProbeCombination (Cytocell Ltd., Cambridge, UK).

Therecurrent constitutionalt(11;22)(q23;q11) is the most frequent non Robertsonian translocation in humans. Similar to Robertsonian translocations and many other recurrent or non recurrent constitutional translocations, balanced carriers of the t(11;22) translocation usually have no clinical symptoms because this rearrangement does not disrupt functional genes. Balanced carriers, however, often have reproductive problems such as male infertility, recurrent pregnancy loss, and the birth of offspring with a chromosomal imbalance. Severely affected offspring have supernumerary der(22)t(11;22) syndrome [5] as a result of a 3:1 meiotic malsegregation of der(22)(4). The clinical features of ES arises from duplication of 22q10-22q11 and duplication of 11q23-qter on the supernumerary der(22) [2]. The exact incidence is unknown. This is a rare syndrome with reported cases of around 100. Male and female balanced carriers have a 0.7 and 3.7% risk of having children with supernumerary der(22), respectively. Clinical testing such as chromosomal analysis, FISH testing, whole chromosome paint (WCP), array genomic hybridization (aGH), or multiple ligation-dependent probe amplification (MLPA) (MRC-Holland, Amsterdam, The Netherlands) assay can be performed for the diagnosis of this syndrome. Highest mortality is in the first few months of life.While the true mortality rate in ES is unknown, long-term survival is possible, especially if the patient survives the infancy period. The reported case had all the classical features of ES [2] (Table 1).

Almost all children with ES have global developmental delays and intellectual disabilities. Table 2 shows the list of clinical features observed in Emanuel syndrome. Management involves a multi disciplinary team approach involving pedodontist, pediatrician, plastic surgeon, geneticist, gastrologist, speech therapist, urologist, cardiologist, ear, nose and throat (ENT) surgeon and ophthalmologist. Two issues are important in terms of genetic counseling of these families. First, when one parent is a carrier of t(11;22), future pregnancies are at an increased risk for either ES, balanced t(11;22), or another meiotic malsegregation, thus, prenatal cytogenetic testing should be offered for future pregnancies. Secondly, carrier testing of the unaffected siblings should normally be offered when they have reached adulthood and are able to understand the reproductive implications of being a carrier [2].

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.