Dataset Information

[Congenital hypopituitarism with monosomy of chromosome 18].

ABSTRACT: Congenital hypopituitarism is a rare disease. It can be caused by isolated inborn defects of the pituitary, gene mutations (PROP1, PIT1), and chromosomal abnormalities.Deletions of chromosome 18 (De Grouchy syndrome types 1 and 2) are a group of rare genetic diseases with a frequency of 1:50,000. Hypopituitarism in these syndromes is detected in from 13 to 56% of cases and depends on the size and location of the deleted segment.We have described a series of clinical cases of patients with congenital hypopituitarism due to deletions in chromosome 18. All children had a characteristic dysmorphic features and delayed mental and speech development. Within first months of life, patients developed muscular hypotension, dysphagia, and respiratory disorders. The patients had various congenital malformations in combination with hypopituitarism (isolated growth hormone deficiency and multiple pituitaryhormone deficiencies). In the neonatal period, there were the presence of hypoglycemia in combination with cholestasis.Hormone replacement therapy led to rapid relief of symptoms.Сhromosomal microarray analysis in 2 patients allowed us to identify exact location of deleted area and deleted genes and optimize further management for them.

SUBMITTER: Bolmasova AV

PROVIDER: S-EPMC9753836 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

[Congenital hypopituitarism with monosomy of chromosome 18].

Bolmasova A V AV Melikyan M A MA Gadzhieva Z Sh ZS Puchkova A A AA Degtyareva A V AV Peterkova V A VA

Problemy endokrinologii 20210713 4

Congenital hypopituitarism is a rare disease. It can be caused by isolated inborn defects of the pituitary, gene mutations (PROP1, PIT1), and chromosomal abnormalities.Deletions of chromosome 18 (De Grouchy syndrome types 1 and 2) are a group of rare genetic diseases with a frequency of 1:50,000. Hypopituitarism in these syndromes is detected in from 13 to 56% of cases and depends on the size and location of the deleted segment.We have described a series of clinical cases of patients with congen ...[more]

PMID: 34533014

Similar Datasets

Project description:BackgroundRing chromosome 18 [r(18)] syndrome represents a relatively rare condition with a complex clinical picture including multiple congenital dysmorphia and varying degrees of mental retardation. The condition is cytogenetically characterized by a complete or mosaic form of ring chromosome 18, with ring formation being usually accompanied by the partial loss of both chromosomal arms. Here we observed a 20-year-old male patient who along with the features typical for r(18) carriers additionally manifested a severe congenital subaortic stenosis. To define the genetic basis of such a compound phenotype, standard cytogenetic and high-resolution molecular-cytogenetic analysis of the patient was performed.Case presentationStandard chromosome analysis of cultured lymphocytes confirmed 46, XY, r(18) karyotype. Array-based comparative genomic hybridization (array-CGH) allowed to define precisely the breakpoints of 18p and 18q terminal deletions, thus identifying the hemizygosity extent, and to reveal an additional duplication adjoining the breakpoint of the 18p deletion. Apart from the terminal imbalances, we found an interstitial microdeletion of 442 kb in size (18q12.1) that encompassed DTNA gene encoding α-dystrobrevin, a member of dystrophin-associated glycoprotein complex. While limited data on the role of DTNA missense mutations in pathogenesis of human cardiac abnormalities exist, a microdeletion corresponding to whole DTNA sequence and not involving other genes has not been earlier described.ConclusionsA detailed molecular-cytogenetic characterization of the patient with multiple congenital abnormalities enabled to unravel a combination of genetic defects, namely, a ring chromosome 18 with terminal imbalances and DTNA whole-gene deletion. We suggest that such combination could contribute to the complex phenotype. The findings obtained allow to extend the knowledge of the role of DTNA haploinsufficiency in congenital heart malformation, though further comprehensive functional studies are required.

Project description:BackgroundCat eye syndrome (CES) is a rare chromosomal disease, with estimated incidence of about 1 in 100,000 live newborns. The classic triad of iris coloboma, anorectal malformations, and auricular abnormalities is present in 40% of patients, and other congenital defects may also be observed. The typical associated cytogenetic anomaly relies on an extra chromosome, derived from an inverted duplication of short arm and proximal long arm of chromosome 22, resulting in partial trisomy or tetrasomy of such regions (inv dup 22pter-22q11.2).Case presentationWe report on a full-term newborn, referred to us soon after birth. Physical examination showed facial dysmorphisms, including hypertelorism, down slanted palpebral fissures, and dysplastic ears with tragus hypoplasia and pre-auricular pit. Ophthalmologic evaluation and heart ultrasound identified left chorioretinal and iris coloboma and ostium secundum type atrial septal defect, respectively. Based on the suspicion of cat eye syndrome, a standard karyotype analysis was performed, and detected an extra small marker chromosome confirming the CES diagnosis. The chromosomal abnormality was then defined by array comparative genome hybridization (a-CGH, performed also in the parents), which identified the size of the rearrangement (3 Mb), and its de novo occurrence. Postnatally, our newborn presented with persistent hypoglycemia and cholestatic jaundice. Endocrine tests revealed congenital hypothyroidism, cortisol and growth hormone (GH) deficiencies, which were treated with replacement therapies (levotiroxine and hydrocortisone). Brain magnetic resonance imaging, later performed, showed aplasia of the anterior pituitary gland, agenesis of the stalk and ectopic neurohypophysis, confirming the congenital hypopituitarism diagnosis. She was discharged at 2 months of age, and included in a multidisciplinary follow-up. She currently is 7 months old and shows a severe global growth failure, and developmental delay. She started GH replacement treatment, and continues oral hydrocortisone, along with ursodeoxycholic acid and levothyroxine, allowing an adequate control of glycemic and thyroid profiles as well as of cholestasis.ConclusionsCES phenotypic spectrum is wide and highly variable. Our report highlights how among the possible associated endocrine disorders, congenital hypopituitarism may occur, leading to persistent hypoglycemia and cholestasis. These patients should be promptly assessed for complete hormonal evaluations, in addition to major malformations and midline anomalies. Early recognition of such defects is necessary to decrease fatal events, as well as short and long-term related adverse outcomes.

Dataset Information

[Congenital hypopituitarism with monosomy of chromosome 18].

Publications

[Congenital hypopituitarism with monosomy of chromosome 18].

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets