title: Hypomyelination and congenital cataract: broadening the clinical phenotype.
abstract: OBJECTIVE
  To further delineate the clinical spectrum of hypomyelination and congenital cataract (HCC), a rare autosomal recessive white matter disorder due to deficiency of a membrane protein, hyccin, encoded by FAM126A.
  
  
  METHODS
  Case reports and literature review.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Nine additional patients with HCC.
  
  
  RESULTS
  Cataract was congenital in 5 patients; it was found at 4, 5, and 7 months in 3 patients, and only a mild lens opacity was noted at age 3 years in the remaining patient. Neurologic presentation was at birth in 1 child, was characterized by developmental delay at the end of the first year of life in 7 patients, and was characterized by sudden motor regression in the second year of life in the remaining patient. Three patients were able to walk with support only, 5 achieved the ability to walk without support, and the remaining patient was not able to stand at age 2 years. Mental retardation was present in all patients. Peripheral neuropathy was present in the 8 patients who underwent neurophysiological investigations. Brain magnetic resonance imaging showed hypomyelination associated with periventricular white matter abnormalities in all patients and brainstem pyramidal tract involvement in 8. Molecular analysis depicted 3 novel mutations and the previously reported IVS5 + 1G>T mutation.
  
  
  CONCLUSIONS
  Our study broadens the clinical spectrum of HCC. The clinical variability ranges from severe early-onset neurologic impairment to a milder phenotype. In contrast to this clinical variability, the peculiar magnetic resonance pattern of hypomyelination combined with increased periventricular white matter water content allows distinction of HCC from other forms of hypomyelinating leukoencephalopathies.
authors.affiliation: Department of Neuroscience, G. Gaslini Institute, Genova, Italy. roberta@biancheri.com
authors.forename: Roberta
authors.initials: R
authors.lastname: Biancheri
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
authors.forename: Andrea
authors.initials: A
authors.lastname: Rossi
authors.forename: Mikael
authors.initials: M
authors.lastname: Mathot
authors.forename: Marie Cecile
authors.initials: MC
authors.lastname: Nassogne
authors.forename: Cengiz
authors.initials: C
authors.lastname: Yalcinkaya
authors.forename: Ozdem
authors.initials: O
authors.lastname: Erturk
authors.forename: Behyan
authors.initials: B
authors.lastname: Tuysuz
authors.forename: Maja
authors.initials: M
authors.lastname: Di Rocco
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gazzerro
authors.forename: Marianna
authors.initials: M
authors.lastname: Bugiani
authors.forename: Resie
authors.initials: R
authors.lastname: van Spaendonk
authors.forename: Erik A
authors.initials: EA
authors.lastname: Sistermans
authors.forename: Carlo
authors.initials: C
authors.lastname: Minetti
authors.forename: Marjo S
authors.initials: MS
authors.lastname: van der Knaap
authors.forename: Nicole I
authors.initials: NI
authors.lastname: Wolf
mesh_terms: D002386:Cataract / Q000175:diagnosis* / Q000235:genetics*; D002675:Child, Preschool; D003711:Demyelinating Diseases / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D010641:Phenotype; D012720:Severity of Illness Index
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C412048:HYCC1 protein, human