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

Abstract

Background Rearrangements of unstable DNA sequences may alter the structural integrity or the copy number of dose-sensitive genes, resulting in copy number variations. They may lead more frequently to deletions, in addition to duplications and/or inversions, which are the underlying pathogenic mechanism of a group of conditions known as genomic disorders (or also contiguous gene syndromes). Interstitial deletions of the short arm of chromosome 1 are rare, and only about 30 patients have been reported. Their clinical features are variable, in respect of the extent of the deleted region. They include global developmental delay, central nervous system (CNS) malformations, craniosynostosis, dysmorphic face, ocular defects, cleft palate, urinary tract anomalies and hand/foot abnormalities. Case presentation Hereby, we report on an Italian female newborn with craniosynostosis, facial dysmorphisms including bilateral microphthalmia and coloboma, cleft palate, and a severe global developmental and growth delay, associated to a 1p31.3p22.2 deletion of 20.7 Mb. This was inherited from the healthy mother, who was carrier of a smaller (2.6 Mb) deletion included within the centromeric region (1p22.3p22.2) of the same rearrangement, in addition to a translocation between chromosomes 1p and 4q. The deleted region of the proband contains about ninety genes. We focus on the genotype–phenotype correlations. Conclusions The results of the present study further confirm that microdeletions at 1p31.3 constitute a contiguous gene syndrome. It is hard to establish whether the critical rearrangement of such syndrome may involve the centromeric band p22.3p22.2, or more likely do not, also in light of the genomic profile of the healthy mother of our patient. Neonatologists and pediatricians should take into consideration 1p31 microdeletion in cases of developmental and growth delay associated to craniosynostosis, peculiar facial dysmorphisms, cleft palate and hand/foot abnormalities. The present report provides new data about 1p31 microdeletion syndrome, in view of a better characterization of its genomic and phenotypic profile.

Novel mutations of the ABCA12, KRT1 and ST14 genes in three unrelated newborns showing congenital ichthyosis

“…Our report highlights the relevant genetic heterogeneity and phenotypic variability of CI. It underlines how for neonatologists and pediatricians may be crucial to achieve the molecular characterization of CI, similarly to other congenital genetic diseases, to make a correct and more precise prognosis evaluation, and to allow proper management based on an individualized approach, as well as adequate genetic counseling [ 9 , 24 , 25 ]. This latter, which includes discussion of potential risks of transmission to offspring and reproductive options, should be offered, if possible before pregnancy, to young adults who are affected or at risk.…”

Congenital hypopituitarism and multiple midline defects in a newborn with non-familial Cat Eye syndrome

“…We strongly recommend glycemic and hormone screening of CES patients, to prevent potential life-threatening conditions. A multidisciplinary (auxological/endocrinological, neurodevelopmental, surgical, ophthalmological, audiological, cardiological, orthopedic) management and longitudinal follow-up [21][22][23][24][25][26][27] must be guaranteed to affected subjects. The latter should be oriented to a prompt recognizing of complications and/or associated anomalies [28][29][30][31][32][33][34], allowing practitioners to thus lower mortality rates and short-and long-term adverse outcomes [35][36][37].…”

Congenital hypopituitarism and multiple midline defects in a newborn with non-familial Cat Eye syndrome

“…We strongly recommend glycemic and hormone screening of CES patients, to prevent potential life-threatening conditions. A multidisciplinary (endocrinological, neurodevelopmental, surgical, ophthalmological, audiological, cardiological, orthopedic) management and longitudinal follow-up [15][16][17][18] must be guaranteed to affected subjects. This latter should be oriented to a prompt recognizing of complications and/or associated anomalies [19][20][21][22], allowing thus to lower mortality rates and short-and long-term adverse outcomes [23][24][25][26].…”