Friday, July 10, 2020

Emanuel syndrome

Inspired by a colleague's patient

Emanuel BS, Zackai EH, Medne L. Emanuel Syndrome. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993.

Clinical characteristics: Emanuel syndrome is characterized by pre- and postnatal growth deficiency, microcephaly, hypotonia, severe developmental delays, ear anomalies, preauricular tags or pits, cleft or high-arched palate, congenital heart defects, kidney abnormalities, and genital abnormalities in males.

Diagnosis/testing: 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)].

Management: Treatment of manifestations: Care by a multidisciplinary team is usually necessary; standard management of gastroesophageal reflux, nutrition, anal atresia (or stenosis), inguinal hernias, cardiac defects, cleft palate, hip dysplasia, other skeletal complications, hearing loss, cryptorchidism and/or micropenis, refractive errors, and strabismus or other ophthalmologic issues; ongoing physical, occupational, and speech therapies; alternative communication methods to facilitate communication. Prevention of secondary complications: Attention to the airway during sedation and/or operative procedures in an institution with pediatric anesthesiologists. Surveillance: Follow up as needed based on the extent of systemic involvement in each individual; regular developmental assessments; periodic reevaluation by a clinical geneticist.

Genetic counseling: In more than 99% of cases, one of the parents of a proband with Emanuel syndrome is a balanced carrier of a t(11;22)(q23;q11.2) and is phenotypically normal. In most cases, a carrier parent has inherited the t(11;22) from one of his or her parents. When one of the parents of a proband is a carrier of the balanced t(11;22), possible outcomes of future pregnancies of the parents include: normal chromosomes, supernumerary der(22) syndrome, balanced t(11;22) carrier, and spontaneous abortion as a result of supernumerary der(22) or another meiotic malsegregant. Risks vary depending on whether the mother or father of a proband is the balanced translocation carrier. Prenatal diagnosis for pregnancies at increased risk is possible if the chromosome abnormality has been confirmed in the family.

Xie CL, Cardenas AM. Neuroimaging findings in Emanuel Syndrome. J Radiol Case Rep. 2019;13(10):1-5. Published 2019 Oct 31. doi:10.3941/jrcr.v13i10.3625

Emanuel syndrome is a rare inherited chromosomal abnormality caused by an unbalanced translocation of chromosomes 11 and 22. Clinically, Emanuel syndrome is characterized by a wide spectrum of congenital anomalies, dysmorphisms, and developmental disability often confused with other similar syndromes. Outside of genetic testing, diagnosis remains challenging and current literature on typical radiologic findings is limited. We present classic neuroimaging findings of Emanuel syndrome consistent with prior literature including microcephaly, microretrognathia, external auditory canal stenosis, and cleft palate; and also introduce the additional maxillofacial anomaly of dysplastic middle ear ossicles, to our knowledge not previously described in the literature. Recognition of findings leading to earlier diagnosis of Emanuel syndrome may improve outcomes and quality of life for patients and their families.

Liehr T, Acquarola N, Pyle K, et al. Next generation phenotyping in Emanuel and Pallister-Killian syndrome using computer-aided facial dysmorphology analysis of 2D photos. Clin Genet. 2018;93(2):378-381. doi:10.1111/cge.13087

High throughput approaches are continuously progressing and have become a major part of clinical diagnostics. Still, the critical process of detailed phenotyping and gathering clinical information has not changed much in the last decades. Forms of next generation phenotyping (NGP) are needed to increase further the value of any kind of genetic approaches, including timely consideration of (molecular) cytogenetics during the diagnostic quest. As NGP we used in this study the facial dysmorphology novel analysis (FDNA) technology to automatically identify facial phenotypes associated with Emanuel (ES) and Pallister-Killian Syndrome (PKS) from 2D facial photos. The comparison between ES or PKS and normal individuals expressed a full separation between the cohorts. Our results show that NPG is able to help in the clinic, and could reduce the time patients spend in diagnostic odyssey. It also helps to differentiate ES or PKS from each other and other patients with small supernumerary marker chromosomes, especially in countries with no access to more sophisticated genetic approaches apart from banding cytogenetics. Inclusion of more facial pictures of patient with sSMC, like isochromosome-18p-, cat-eye-syndrome or others may contribute to higher detection rates in future.

Luo JW, Yang H, Tan ZP, et al. A clinical and molecular analysis of a patient with Emanuel syndrome. Mol Med Rep. 2017;15(3):1348-1352. doi:10.3892/mmr.2017.6107

Emanuel syndrome (ES) is the most frequent type of recurrent nonRobertsonian translocation that is characterized by numerous anomalies. Over 100 patients with ES have been described in the literature. The phenotype of this syndrome varies but often consists of facial dysmorphism, microcephaly, severe intellectual disability, developmental retardation, congenital heart disease and genital anomalies. The present study describes a 2yearold boy with multiple malformations, including facial dysmorphism, severe intellectual disability, growth retardation, congenital heart disease, cleft lip and palate, genital malformation (micropenis), amblyopia, thymic dysplasia and hearing impairment. The karyotype of the patient was 47,XY,+del(22)(q13), and the maternal karyotype was 46,XX,t(11;22)(q25;q13),9qh,15p+. Singlenucleotide polymorphismarray analysis of the proband indicated a partial duplication of chromosomes 22 and 11 at 22q11.1q11.21 and 11q23.3q25, respectively, which confirmed the diagnosis of ES. To date, no cases of ES have been reported in mainland China. The present case further emphasizes the necessity and importance of highresolution techniques for genetic diagnosis and for subsequent genetic counseling. The present study contributed to the phenotypic delineation of ES and confirmed the first ES patient in mainland China.

No comments:

Post a Comment