エマヌエル症候群

OBJECTIVE: To report on two fetuses with supernumerary small marker chromosomes (sSMC) derived from complex rearrangements and explore their genotype-phenotype correlation. METHODS: Two pregnant women who presented at the Prenatal Diagnosis Center of Taizhou Hospital of Zhejiang Province for a high risk signaled by noninvasive prenatal testing (NIPT) were selected as study subjects. Amniotic fluid and peripheral blood samples were collected and subjected to chromosomal karyotyping analysis and copy number variation sequencing (CNV-seq). Databases were searched for similar cases reported in the literature, and the correlation between genotype and phenotype was analyzed. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: K20250822). RESULTS: The karyotype of fetus 1 was identified as 47,XY,+der(22)t(11;22)(q23.3;q11.2)dmat. CNV-seq analysis revealed an 18.1 Mb duplication in the 11q23.3q25 region and a 4.26 Mb duplication in the 22q11.1q11.21 region. The fetus was diagnosed with Emanuel syndrome, and the der(22) has originated from a balanced translocation t(11;22)(q23;q11.2) carried by the mother. The karyotype of fetus 2 was determined as 47,XY,+mar mat, and CNV-seq indicated a 13.06 Mb duplication in the 18p11.32p11.21 region. The fetus' partial 18p trisomy was inherited from its phenotypically normal mother. CONCLUSION: NIPT has value in screening for fetuses with sSMCs. Chromosomal karyotyping combined with CNV-Seq can elucidate the size and genetic content of the sSMCs, thereby facilitating prenatal diagnosis and genetic counseling. Prenatal findings for fetuses with Emanuel syndrome primarily include posterior cranial fossa abnormalities, ventricular enlargement, cardiac developmental anomalies, and increased nuchal translucency. Trisomy 18p caused by sSMC is associated with mild malformations.

Congenital diaphragmatic hernia (CDH) diagnosed in the first or early second trimester is exceedingly rare. We herein present a unique case of Emanuel syndrome identified through early sequential findings of increased nuchal translucency (NT) and CDH. A 34-year-old Japanese woman was referred at 14 weeks of gestation because of an elevated NT of 3.9 mm detected at 12 weeks, with no other markers of aneuploidy. At 15+1/7 weeks, an ultrasound revealed right-sided heart displacement, a tubular structure near the heart, and a cystic structure on the left, presumed to be the stomach and intestines, respectively-findings indicative of CDH. Fetal karyotyping via amniocentesis confirmed Emanuel syndrome with a karyotype of 47,XY,+der(22) t(11;22)(q23.3;q11.2). This case suggests that early detection of increased NT could lead to the early diagnosis of CHD, which, in our case, was part of Emanuel syndrome.

INTRODUCTION: Emanuel syndrome is a rare chromosomal disorder characterized by severe developmental disability and variable clinical manifestations. Although congenital anomalies are relatively common, there is no pathognomonic prenatal pattern. In some cases, structural defects are absent or not detectable prenatally, making the potential role of soft ultrasound markers particularly relevant. CASE PRESENTATION: We report a case of Emanuel syndrome in which no structural malformations were identified prenatally. First-trimester ultrasound revealed an isolated increased nuchal translucency of 3.2 mm. Postnatally, the infant exhibited severe hypotonia, dysmorphic features, and profound developmental delay, but no gross structural defects were observed. Cytogenetic and FISH analyses confirmed an additional der(22)t(11; 22) chromosome inherited from the mother. DISCUSSION: A review of the limited literature on first-trimester findings suggests that increased nuchal translucency has been observed in several cases of Emanuel syndrome, although the available data remain insufficient to assess predictive value. Nevertheless, the recurrence of this observation across independent reports indicates that NT enlargement may warrant attention as a potential prenatal marker. CONCLUSION: While current evidence is insufficient to draw definitive conclusions, this case highlights that isolated NT thickening may represent the only prenatal sign of Emanuel syndrome. Evaluation in larger cohorts and future prospective studies will be essential to determine the sensitivity and specificity of this marker for early diagnosis of the syndrome and the timely identification of balanced translocation carriers.

OBJECTIVE: Emanuel syndrome is a rare inherited chromosomal disorder characterized by the presence of a derivative chromosome 22 resulting from a translocation between chromosomes 11 and 22. Since the number of reported cases in Asian is still small, we mean to present 2 more cases diagnosed prenatally and review similar case reports to better understand the syndrome when abnormal findings were found prenatally. CASE REPORT: Two cases of Emanual syndrome were found where one draws attention due to abnormal serum marker and thickened nuchal translucency, and the other was found when prenatal ultrasonography detected multiple anomalies. Genetic amniocentesis revealed 47 chromosomes gaining an additional marker chromosome arising from malsegregation in a balanced translocation heterozygote with 46, XX, t(11;22) (q23.3;q11.2). CONCLUSION: While different anomalies were found, both of our cases along with others presented 3:1 segregation with tertiary trisomy resulting in Emanual syndrome. Chromosome of the quadrivalent is small in content ("lop-sided" quadrivalent) at meiosis I, which tends to separate in a 3:1 segregation fashion.

The 22q11.2 region is highly susceptible to genomic rearrangements leading to multiple genomic disorders, including 22q11.2 microdeletion syndrome (22q11.2 DS) (MIM# 188400), 22q11.2 microduplication syndrome (MIM# 608363), supernumerary der(22)t(11;22) syndrome (also known as Emanuel Syndrome; MIM# 609029), and Cat Eye Syndrome (MIM# 115470). In this study, we present data on causes of mortality, average age of death, and the existing associated risk factors in patients with 22q11.2 rearrangements. Our cohort included 223 patients (120 males and 103 females) with confirmed diagnoses of 22q11.2 rearrangements diagnosed through molecular techniques (FISH, MLPA, and CMA). Relatives from patients who have been molecularly confirmed with 22q11.2 rearrangements have also been added to the study, regardless of the presence or absence of symptoms. Of these 223 individuals, 21 (9.4%) died. Deceased patients' rearrangements include 19 microdeletions, 1 microduplication, and 1 patient with a marker chromosome. The median age of death was 3 months and 18 days (ranging from 3 days to 34 years). There were 17 patients who died at pediatric age (80.95%), 3 died at adult age (14.28%), and for 1 of whom, the age of death is unknown (4.76%). Eighteen patients were White Mediterranean (European non-Finnish) (85.71%) whereas three were Amerindian (South American) (14.28%). Mortality from cardiac causes accounted for 71.42%. The second most frequent cause of death was sepsis in two patients (9.52%). One patient died from respiratory failure (4.76%) and one from renal failure (4.76%). Information regarding the cause of death was not available in two patients (9.52%). Most patients who died were diagnosed within the first week of life, the majority on the first day. This study adds additional information on mortality in one of the largest cohorts of patients with 22q11.2 rearrangements in more than 30 years of follow-up.