Abstract

Microdeletion syndromes include numerous syndromic phenotypes associated with intellectual disability and dysmorphic features. We report on a patient with a novel microdeletion of chromosomal region 3p11.2-p12.1 containing POU1F1, chromatin-modifying protein 2B (CHMP2B), and vestigial-like 3 (VGLL3) genes. Our patient was diagnosed as having a neonatal multiple pituitary hormone [growth hormone (GH), thyroid-stimulating hormone (TSH), and prolactin] deficiency. In addition to the typical findings associated with these hormonal deficiencies, she exhibited clinical features resembling those of Laron syndrome (frontal bossing, saddle nose, small chin, blue sclera, and acromicria), with moderate intellectual disability. She also displayed an unusual growth pattern characterized by unresponsiveness to high doses of GH replacement therapy during infancy and early childhood and an accelerated growth rate beginning at the age of 4.5 years. Insulin-like growth factor (IGF)-1 levels were consistently extremely low or undetectable. Extensive medical and genetic analysis ruled out primary and secondary GH insensitivity. The distinct phenotype and the peculiar growth pattern observed in this affected patient, not reported to have been observed in other cases with POU1F1 gene inactivity, suggest that the other two deleted genes play a possible role in the development of this syndrome. This hypothesis may be supported by the fact that both the CHMP2B and VGLL3 genes are expressed in the liver and the growth plate, the two main target organs of the GH/IGF-1 axis. The homozygous deletion of the CHMP2B gene, previously associated with frontotemporal dementia, may contribute to the intellectual disability observed in this patient.

Links

Publisher Full Text

Authors

Gat-Yablonski G, Frumkin-Ben David R, Bar M, Potievsky O, Phillip M, Lazar L

Institution

The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children's Medical Center of Israel, Petah Tiqwa, Israel. galiagy@post.tau.ac.il

Source

American journal of medical genetics. Part A 155A:9 2011 Sep pg 2242-6

MeSH

Abnormalities, Multiple
Child
Chromosome Deletion
Chromosomes, Human, Pair 3
Endosomal Sorting Complexes Required for Transport
Female
Growth Hormone
Humans
Insulin-Like Growth Factor I
Intellectual Disability
Israel
Laron Syndrome
Liver
Premature Birth
Prolactin
Thyrotropin
Transcription Factor Pit-1
Transcription Factors

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21815258