Dysmorphic Features, Frontal Cerebral Cavernoma, and Hyperglycemia in a Girl with a De Novo Deletion of 7.23 Mb in Region 7p13-p12.1.

Abstract

We describe the case of a 7-year-old girl referred to our diabetes unit for hyperglycemia associated with facial dysmorphic features, intellectual disability, and cerebral cavernomas. Based on presence of anti islet antigen-2 (IA2) antibodies and a human leukocyte antigen of DR3/DR4/DQ2, the patient was initially diagnosed to be a case of type 1 diabetes mellitus. At follow-up, the very good metabolic control on a low insulin dose and negative IA2 antibodies led to a suspicion of glucokinase (GCK)-related maturity-onset diabetes of the young (MODY 2). This suspicion was substantiated in multiplex ligation-dependent probe amplification (MLPA) which showed a heterozygous GCK deletion (exons 1 to 12). However, the patient's parents did not have such a deletion and were clinically euglycemic. Given the clinical picture and the MLPA findings, array based comparative genomic hybridization was performed showing a monoallelic deletion of 7.23 Mb in the short arm of chromosome 7 (7p13-p12.1). The deleted intervals contain 39 genes listed in the Online Mendelian Inheritance in Man list, including GCK associated with MODY 2, CCM2 associated with type 2 cerebral cavernous malformations, IGFBP-3 associated with decrease in postnatal growth, and OGD associated with alpha-ketoglutarate dehydrogenase deficiency, with cognitive impairment and movement abnormalities. This previously unreported deletion was considered to explain the clinical picture of the patient. Also, the findings suggest that 7p13-p12.1 contains genes involved in intellectual disability and craniofacial development.

• Authors: Gilberto Pérez López, Beatriz Villafuerte Quispe, María José Cabrejas Núñez, Luis Castaño, Raquel Barrio
• Journal: Journal of clinical research in pediatric endocrinology (J Clin Res Pediatr Endocrinol) Vol. 9 Issue 4 Pg. 355-359 (Dec 15 2017) ISSN: 1308-5735 [Electronic] Turkey
• PMID: 28387648 (Publication Type: Case Reports, Journal Article)

Topics

• Child
• Chromosome Deletion
• Chromosomes, Human, Pair 7
• Craniofacial Abnormalities (complications, genetics)
• Diabetes Mellitus, Type 2 (complications, genetics)
• Female
• Humans
• Hyperglycemia (complications, genetics)
• Intellectual Disability (complications, genetics)
• Micrognathism (complications, genetics)
• Ribs (abnormalities)