Goldberg-Shprintzen megacolon syndrome with associated sensory motor axonal neuropathy.

Abstract

Goldberg-Shprintzen megacolon syndrome (GOSHS) (OMIM 609460) is characterized by a combination of learning difficulties, characteristic dysmorphic features and Hirschsprung's disease. Variable clinical features include iris coloboma, congenital heart defects and central nervous system abnormalities, in particular polymicrogyria. GOSHS has been attributed to recessive mutations in KIAA1279, encoding kinesin family member (KIF)-binding protein (KBP) with a crucial role in neuronal microtubule dynamics. Here we report on a 7-year-old girl with GOSHS as a result of a homozygous deletion of exons 5 and 6 of the KIAA1279 gene. She had been referred with the suspicion of an underlying neuromuscular disorder before the genetic diagnosis was established, prompted by the findings of motor developmental delay, hypotonia, ptosis and absent reflexes. Neurophysiological studies revealed unequivocal evidence of a peripheral axonal sensory motor neuropathy. We hypothesize that an axonal sensory motor neuropathy may be part of the phenotypical spectrum of KIAA1279-related GOSHS, probably reflecting the effects of reduced KBP protein expression on peripheral neuronal function.

• Authors: Hormos Salimi Dafsari, Susan Byrne, Jean-Pierre Lin, Matthew Pitt, Jan Dh Jongbloed, Frances Flinter, Heinz Jungbluth
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 167 Issue 6 Pg. 1300-4 (Jun 2015) ISSN: 1552-4833 [Electronic] United States
• PMID: 25846562 (Publication Type: Case Reports, Journal Article)
• Copyright: © 2015 Wiley Periodicals, Inc.

Chemical References

• KIFBP protein, human
• Nerve Tissue Proteins

Topics

• Base Sequence
• Child
• Craniofacial Abnormalities (genetics, metabolism, pathology)
• Exons
• Female
• Gene Expression
• Hereditary Sensory and Motor Neuropathy (genetics, metabolism, pathology)
• Hirschsprung Disease (genetics, metabolism, pathology)
• Humans
• Molecular Sequence Data
• Nerve Tissue Proteins (deficiency, genetics)
• Sensory Receptor Cells (metabolism, pathology)
• Sequence Deletion