Jacobsen syndrome and neonatal bleeding: report on two unrelated patients

Abstract

Introduction In 1973, Petrea Jacobsen described the first patient showing dysmorphic features, developmental delay and congenital heart disease (atrial and ventricular septal defect) associated to a 11q deletion, inherited from the father. Since then, more than 200 patients have been reported, and the chromosomal critical region responsible for this contiguous gene disorder has been identified. Patients’ presentation We report on two unrelated newborns observed in Italy affected by Jacobsen syndrome (JBS, also known as 11q23 deletion). Both patients presented prenatal and postnatal bleeding, growth and developmental delay, craniofacial dysmorphisms, multiple congenital anomalies, and pancytopenia of variable degree. Array comparative genomic hybridization (aCGH) identified a terminal deletion at 11q24.1-q25 of 12.5 Mb and 11 Mb, in Patient 1 and 2, respectively. Fluorescent in situ hybridization (FISH) analysis of the parents documented a de novo origin of the deletion for Patient 1; parents of Patient 2 refused further genetic investigations. Conclusions Present newborns show the full phenotype of JBS including thrombocytopenia, according to their wide 11q deletion size. Bleeding was particularly severe in one of them, leading to a cerebral hemorrhage. Our report highlights the relevance of early diagnosis, genetic counselling and careful management and follow-up of JBS patients, which may avoid severe clinical consequences and lower the mortality risk. It may provide further insights and a better characterization of JBS, suggesting new elements of the genotype-phenotype correlations.

Interstitial deletions of chromosome 1p: novel 1p31.3p22.2 microdeletion in a newborn with craniosynostosis, coloboma and cleft palate, and review of the genomic and phenotypic profiles

“…3 ). The results of present study further confirm that microdeletions at 1p31.3 constitute a contiguous gene syndrome, whose genotype–phenotype correlations are still only partially elucidated, due to variability both in phenotype expressivity and deletion size typical of genomic disorders [ 24 – 26 ]. Further characterization of this genomic region, analysis of other patients, and functional studies will provide more insights both on the number and type of critical genes and their impact on this contiguous gene syndrome.…”

Cardio-facio-cutaneous syndrome and gastrointestinal defects: report on a newborn with 19p13.3 deletion including the MAP 2 K2 gene

“…Our patient shows cerebellar hypoplasia and mild developmental delay, but no hematological (platelet alterations), metabolic (lipidic profile), and ocular abnormalities, although the appearance of such anomalies over time cannot be ruled out. The other genes in the deleted region may also play a causative role for the phenotype, but it is hard to establish their involvement as well as genotype-phenotype correlations [ 19 , 20 ]. However, our results support the evidence of 19p13.3 microdeletion as contiguous gene syndrome, in which some of the genes contiguous to MAP 2 K2 may modify patients’ phenotype (e.g.…”

Intestinal malrotation in a female newborn affected by Osteopathia Striata with Cranial Sclerosis due to a de novo heterozygous nonsense mutation of the AMER1 gene

“…The genomic and phenotypic ndings of the present patient may add to current database, and provide a better characterization of such rare disease. Additional patients and the identi cation of new mutations will increase the knowledge on the molecular bases and the pathogenic mechanisms underlying OS-CS [21][22][23][24][25][26][27]. Neonatologists and pediatricians have to rise such diagnostic suspicion in cases of newborns/infants with macrocephaly (also relative if compared to weight and length, as in our proposita), peculiar dysmorphic features including frontal bossing, dysplastic ears, hypertelorism, cleft palate and micrognathia, in addition to limbs anomalies.…”