A novel de novo KIF21A mutation in a patient with congenital fibrosis of the extraocular muscles and Möbius syndrome.
OBJECTIVE
To describe the phenotypic characteristics and clinical course of a sporadic case of congenital fibrosis of the extraocular muscles (CFEOM) and Möbius syndrome with a de novo mutation in the KIF21A gene encoding a kinesin motor protein.


METHODS
An individual with the rare combination of CFEOM and Möbius syndrome underwent comprehensive ophthalmologic and neurological evaluations. Magnetic resonance imaging (MRI) including diffusion tensor imaging (DTI) tractigraphy at 3T field strength was used to evaluate orbital, encephalic, and intracranial nerve integrity. The proband and her healthy parents underwent screening for mutations in the KIF21A, PHOX2A, and TUBB3 genes.


RESULTS
The patient exhibited congenital, nonprogressive, bilateral external ophthalmoplegia, bilateral ptosis, bilateral facial palsy, and developmental delay. Her inability to blink resulted in severe exposure keratopathy and subsequent corneal perforation requiring a penetrating keratoplasty. MRI revealed an unremarkable configuration of the axial central nervous system and preservation of the intracranial portion of cranial nerves I, II, III, V, VI, VII, and VIII (cranial nerve IV is not normally visualized by MRI). A novel and de novo heterozygous KIF21A mutation (c.1056C>G, p.Asp352Glu) in a highly conserved region of the gene was present in the proband.


CONCLUSIONS
The reported KIF21A D352E mutation and associated phenotype further expand the clinical and mutational spectrum of CFEOM and Möbius syndrome.
University of Texas Southwestern Medical Center, Department of Ophthalmology, Dallas, TX.
Zahra
Z
Ali
University of Texas Southwestern Medical Center, McDermott Center for Human Growth and Development / Center for Human Genetics, Dallas, TX.
Chao
C
Xing
University of Texas Southwestern Medical Center, Department of Ophthalmology, Dallas, TX.
Didar
D
Anwar
University of Texas Southwestern Medical Center, Department of Ophthalmology, Dallas, TX.
Kamel
K
Itani
University of Texas Southwestern Medical Center, Department of Ophthalmology, Dallas, TX.
David
D
Weakley
University of Texas Southwestern Medical Center, Department of Ophthalmology, Dallas, TX.
Xin
X
Gong
University of Texas Southwestern Medical Center, Rare Brain Disorders Program, Departments of Neurology and Neurotherapeutics, Physiology and Pediatrics, Dallas, TX.
Juan M
JM
Pascual
University of Texas Southwestern Medical Center, Department of Ophthalmology, Dallas, TX ; University of Texas Southwestern Medical Center, McDermott Center for Human Growth and Development / Center for Human Genetics, Dallas, TX.
V Vinod
VV
Mootha
D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D015785:Eye Diseases, Hereditary / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005355:Fibrosis / Q000235:genetics* / Q000503:physiopathology; D005403:Fixation, Ocular; D006801:Humans; D016547:Kinesins / Q000737:chemistry / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D020331:Mobius Syndrome / Q000235:genetics* / Q000503:physiopathology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D015835:Ocular Motility Disorders / Q000235:genetics* / Q000503:physiopathology
C119023:KIF21A protein, human; D016547:Kinesins