Abstract Details

Title Phenotypic Differences in Identical Twins with Mutated WDR45, a Newly Discovered X-Chromosome Gene Mutation Which Causes Neurodegeneration with Brain Iron Accumulation (NBIA)

Topic Movement Disorders

Presentation(s) P03 - (-)

Poster/Presentation
Number 052

Objective

Background BACKGROUND: Several gene mutations cause NBIA and patients have unique clinical neurological and neuroimaging findings depending on the gene involved. A newly discovered NBIA entity is caused by mutation of WDR45 gene of the X-chromosome, which encodes a beta-propeller protein. The disease was named beta-propeller protein-associated neurodegeneration (BPAN).

Design/Methods

Results RESULTS: The twin girls are 28 years old. Their birth records indicate that they were monozygotic with one placenta but two amnions. Their mother noted behavioral differences by six months. Twin A developed normally and went to college. Twin B was diagnosed with cerebral palsy, was never toilet trained, could not speak intelligibly and did not attend regular school. Head MRI revealed iron accumulation in the globus pallidus and substantia nigra, bilaterally and in both twins. However, twin B had atrophy of the posterior cerebral hemispheres and ventriculomegaly, more evident on the left, and consistent with perinatal hypoxia. Both twins had congruence in all genes that were tested, including the mutated WDR45 gene. X-inactivation studies showed differential skewing between the twins, with the more severely affected twin showing extreme skewing (90:10) and the less affected twin showing a random pattern (55:45).

Conclusions CONCLUSIONS: (1) When confronted with major phenotypic discordance in monozygotic twins, in utero and perinatal insults are important suspects, especially in monochorionic/diamniotic situations. (2) Patterns of X-inactivation are likely to influence penetrance and expressivity of the BPAN phenotype.

Authors/Disclosures
Sami I. Harik, MD, FAAN PRESENTER	No disclosure on file
Vasuki Dandu, MD (Baptist health)	Dr. Dandu has nothing to disclose.
	No disclosure on file
Susan J. Hayflick, MD, PhD (Oregon Health & Science University)	An immediate family member of Susan J. Hayflick, MD, PhD has received personal compensation for serving as an employee of AbVie. The institution of Susan J. Hayflick, MD, PhD has received research support from NIH. The institution of an immediate family member of Susan J. Hayflick, MD, PhD has received research support from NIH.
Jeffrey D. Rothstein, MD, PhD (Johns Hopkins University)	Dr. Rothstein has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Corcept Therapeutics. Dr. Rothstein has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly Pharmaceuticasl. Dr. Rothstein has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for ALS Journal. The institution of Dr. Rothstein has received research support from ALSA. The institution of Dr. Rothstein has received research support from MDA. The institution of Dr. Rothstein has received research support from Target ALS. The institution of Dr. Rothstein has received research support from Maryland TEDCO. The institution of Dr. Rothstein has received research support from Dept of Defense. The institution of Dr. Rothstein has received research support from National Insitutes of Health. The institution of Dr. Rothstein has received research support from Corsalex. Dr. Rothstein has received intellectual property interests from a discovery or technology relating to health care.

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