Deena Godfrey1, Alcy Torres2, Gena Heidary3, Hovra Zahoor2, Arthur Lee4, Gerard Berry5, Elizabeth Engle3,4,6,7. 1. Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA. 2. Department of Pediatrics, Boston Medical Center, Boston, Massachusetts, USA. 3. Ophthalmology, Boston Children's Hospital, Boston, Massachusetts, USA. 4. Neurology, Boston Children's Hospital, Boston, Massachusetts, USA. 5. Metabolism, Boston Children's Hospital, Boston, Massachusetts, USA. 6. Children's Hospital/Harvard Medical School, Enders 5 - The Children's Hospital, Boston, Massachusetts, USA. 7. Department of ophthalmology, Howard Hughes Medical Institute - Carnegie Institution of Washington, Baltimore, Massachusetts, USA.
Abstract
Background: Duane retraction syndrome and arthrogryposis multiplex congenita have an incidence of approximately 1:1500-1:3000 live births. However, the association of these two entities with a Marcus-Gunn might be a rare and, until now, under-recognized clinical presentation of the Wieacker-Wolff Syndrome.Patient and methods: We report a 7-year-old female with dysmorphic features, global developmental delay, arthrogryposis multiplex congenita (AMC), Duane retraction syndrome (DRS), and unilateral Marcus Gunn jaw winking. Results: Whole Exome Sequencing showed a de novo premature stop codon in ZC4H2. Extensive genetic and metabolic work was negative otherwise and Brain MRI showed delayed non-specific myelination abnormalities. She continues to have significant delays but does not have regression, seizures or other neurological complications. She has required a multidisciplinary approach for the management of her multiple contractures. Conclusion: This case confirms ZC4H2 as a cause of syndromic DRS and extends the ZC4H2 phenotype to include Marcus Gunn jaw winking.
Background: Duane retraction syndrome and arthrogryposis multiplex congenita have an incidence of approximately 1:1500-1:3000 live births. However, the association of these two entities with a Marcus-Gunn might be a rare and, until now, under-recognized clinical presentation of the Wieacker-Wolff Syndrome.Patient and methods: We report a 7-year-old female with dysmorphic features, global developmental delay, arthrogryposis multiplex congenita (AMC), Duane retraction syndrome (DRS), and unilateral Marcus Gunn jaw winking. Results: Whole Exome Sequencing showed a de novo premature stop codon in ZC4H2. Extensive genetic and metabolic work was negative otherwise and Brain MRI showed delayed non-specific myelination abnormalities. She continues to have significant delays but does not have regression, seizures or other neurological complications. She has required a multidisciplinary approach for the management of her multiple contractures. Conclusion: This case confirms ZC4H2 as a cause of syndromic DRS and extends the ZC4H2 phenotype to include Marcus Gunn jaw winking.
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