Prenatal diagnosis and postnatal follow-up of 27 cases with 15q11.2 BP1-BP2 microdeletion syndrome / 中华围产医学杂志

Objective:To summarize the prenatal diagnosis and postnatal follow-up of 15q11.2 BP1-BP2 microdeletion syndrome (Burnside-Butler syndrome, BBS), and provide a reference for the management of BBS.Methods:A retrospective analysis was performed on 27 singleton pregnancies with fetal BBS that were prenatally diagnosed by single nucleotide polymorphism(SNP) array of amniotic fluid in Wuxi Maternity and Child Health Care Hospital from January 2017 to September 2021. Prenatal diagnosis indications, serological screening, prenatal ultrasound features, SNP array results, and postnatal growth and development were described and summarized.Results:(1) Of the 27 cases, the indications of prenatal diagnosis in 14 cases were abnormal sonographic findings, including eight cases with increased nuchal translucency, two with cleft lip and palate/alveolar process cleft, one with fetal multiple joint contracture syndrome, one with fetal right diaphragmatic hernia and single umbilical artery, one with suspected fetal duodenal atresia and one with nasal bone absence. Other indications included high risk of Down syndrome by serological screening in six cases, history of adverse pregnancy in six cases, and advanced age in one case. (2) Karyotyping of amniotic fluid in these 27 BBS fetuses showed normal results and SNP array indicated the deletion range of 311.8-855.3 kb. Parental verification of 23 cases confirmed one was a new mutation, seven were inherited from the father and 15 from the mother. (3) Five pregnancies were terminated in the second trimester and the remaining 22 cases were live births. (4) The median follow-up of the 22 children was 1 year 8 months (range 0.5 months to 4 years 3 months), which found low body weight and/or growth retardation in six cases, low body weight with language retardation in one case, low body weight with growth retardation and hyperactive behavior in one case, language retardation with left ear appendage in one case, cleft palate accompanied by duodenum/cleft lip and alveolar cleft in two cases without abnormal development after surgical treatment, and no abnormal growth in the remaining 11 cases.Conclusion:For BBS fetuses, the proportion of ultrasound abnormalities is high but with a low specificity in prenatal diagnosis, and the risk of abnormal postnatal growth and development/behavior is high, which requires continuous monitoring.

Inherited 15q24 microdeletion syndrome in twins and their father with phenotypic variability.

BACKGROUND: Deletions including chromosome 15q24 have been delineated in recent years as a separate syndrome with phenotypic variability. Here we report a familial 15q24 deletion and further contribute to the phenotypic description of this syndrome. METHODS: Molecular karyotyping and description of the phenotype of three patients in the same family with a 15q24 deletion. RESULTS: Parental transmission of the 15q24 deletion syndrome is described in the same family. The affected, the father and his twin offspring, all exhibit the typical facial features, signs and symptoms consistent with the syndromic phenotype. A distinct phenotypic variability is nevertheless noted although they all share the same deletion. CONCLUSIONS: These three patients are to our knowledge the first described cases of 15q24 syndrome in the same family. Urogenital malformations have previously been described as a part of this syndrome. Our adult male patient exhibits no such malformations but has a documented reduced fertility. This fact points to other factors such as haploinsufficiency of one and/or further genes on 15q24 as being responsible for the infertility. Array analysis could be considered as a first hand analysis in the investigation of cases of infertility and intellectual deficiency in adults in analogy to the existing consensus regarding cases of intellectual deficiency in children.

A rare non-Robertsonian translocation involving chromosomes 15 and 21 / Uma rara translocacao nao robertsoniana envolvendo os cromossomos 15 e 21

CONTEXT: Robertsonian translocations (RT) are among the most common balanced structural rearrangements in humans and comprise complete chromatin fusion of the long arm of two acrocentric chromosomes. Nevertheless, non-Robertsonian translocation involving these chromosomes is a rare event. CASE REPORT: We report a de novo unbalanced translocation involving chromosomes 15 and 21. The newborn was the daughter of a 29-year-old mother and a 42-year-old father. The couple was non-consanguineous. Clinical findings led to the diagnosis of Down syndrome (DS) with severe congenital heart defects (persistent arterial duct, and complete atrioventricular septal defect), as well as low birth length and weight (< 5th and < 10th percentile, respectively, based on specific measurement curves for DS). Conventional cytogenetic analysis revealed the karyotype 46,XX,der(15)(15pter→15q26.2::21q11.2→21qter). The translocation was confirmed by means of fluorescence in situ hybridization. The parents had normal karyotypes. CONCLUSIONS: Differently from RT, in our case a rare event occurred involving the distal segment of 15q and the proximal segment of 21q. Only two reports of this translocation, involving chromosomes 15 and 21 but different breakpoints, have been described so far. The association between 21q duplication and 15q deletion makes it difficult to separate the effect of each chromosome, but might also be responsible for increasing the growth retardation, as detected in our case. Cytogenetic analysis on DS patients is mandatory not only to confirm the diagnosis, but also to assess the risk of recurrence at genetic counseling, as well as to evaluate the contribution of other chromosome aberrations in the final phenotype. .

CONTEXTO: Translocações robertsonianas (TR) estão entre os rearranjos estruturais balanceados mais comuns em humanos e compreendem a fusão da cromatina completa do braço longo de dois cromossomos acrocêntricos. No entanto, são raras as translocações não Robertsonianas envolvendo esses cromossomos. RELATO DE CASO: Nós descrevemos uma translocação não balanceada de novo envolvendo os cromossomos 15 e 21. A recém-nascida era filha de uma mãe de 29 anos e de um pai de 42 anos, casal não consanguíneo. Os achados clínicos levaram ao diagnóstico de síndrome de Down (SD) com defeitos cardíacos congênitos graves (persistência do canal arterial e defeito do septo atrioventricular completo), além de baixos comprimento e peso ao nascimento (< 5o e < 10o percentil em curvas de medidas específicas para SD, respectivamente). A análise citogenética convencional revelou o cariótipo 46,XX,der(15)(15pter→15q26.2::21q11.2→21qter). A translocação foi confirmada por hibridação in situ fluorescente. Os pais apresentavam cariótipo normal. CONCLUSÕES: Diferentemente das TR, nesse caso ocorreu evento raro envolvendo o segmento distal de 15q e o proximal de 21q. Apenas dois relatos dessa translocação, envolvendo os cromossomos 15 e 21 e diferentes pontos de quebra, já foram descritos. A associação entre duplicação 21q e deleção 15q dificulta a distinção dos efeitos de cada cromossomo, mas poderia também ser responsável pelo acentuado retardo de crescimento. A análise citogenética é obrigatória em pacientes com SD não apenas para confirmar o diagnóstico, mas também para avaliar o risco de recorrência no aconselhamento genético, bem como avaliar a contrib...

Autism and mental retardation: the genetic relationship and contribution

Autism, a neurodevelopmental disorder first described in 1943, is reviewed. The signs and symptoms of the disorder are described together with the etiological factors. The evidence for a genetic etiology of autism and its association with other genetic disorders are discussed. Possible candidate genes for autism are described