title: The clinical spectrum of nodular heterotopias in children: report of 31 patients.
abstract: OBJECTIVE
  The phenotypic and etiologic spectrum in adults with nodular heterotopias (NHs) has been well characterized. However, there are no large pediatric case series. We, therefore, wanted to review the clinical features of NHs in our population.
  
  
  METHODS
  Hospital records of 31 patients with pathology or imaging-confirmed NHs were reviewed. Two-sided Fisher's exact t-test was used to assess associations between distribution of NHs and specific clinical features.
  
  
  RESULTS
  NHs were distributed as follows: 8 (26%) unilateral focal subependymal, 3 (10%) unilateral diffuse subependymal, 5 (16%) bilateral focal subependymal, 12 (39%) bilateral diffuse subependymal, and 3 (10%) isolated subcortical. The phenotypic spectrum in our population differs from that described in adults. Significant morbidity and mortality are associated with presentation in childhood. Twenty-two of 31 patients (71%) died in the neonatal period or in childhood. Additional cerebral malformations were found in 80% and systemic malformations in 74%. The majority of patients had developmental delay, intellectual deficit, and intractable epilepsy. Patients with unilateral focal NHs were more likely to have ventriculomegaly (p = 0.027), and those with bilateral diffuse NHs more likely to have cerebellar abnormalities (p = 0.007). Isolated subcortical NHs were associated with multiple malformations (p = 0.049) and cardiac abnormalities (p = 0.027). Underlying etiology was heterogeneous and determined in only six cases (19%): del chr 1p36, del chr 15q11, pyruvate dehydrogenase deficiency, sialic acidosis type 1, Aicardi syndrome, and FLNA mutation.
  
  
  CONCLUSIONS
  NHs are present in childhood as part of multiple cerebral and systemic malformations; developmental delay and refractory seizures are the rule rather than the exception. Milder forms go unrecognized until seizure onset in adulthood.
authors.affiliation: Centre de recherche du CHUM, Montréal, Université de Montréal, Quebec, Canada.
authors.forename: Myriam
authors.initials: M
authors.lastname: Srour
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Rioux
authors.forename: Caroline
authors.initials: C
authors.lastname: Varga
authors.forename: Anne
authors.initials: A
authors.lastname: Lortie
authors.forename: Philippe
authors.initials: P
authors.lastname: Major
authors.forename: Yves
authors.initials: Y
authors.lastname: Robitaille
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Décarie
authors.forename: Jacques
authors.initials: J
authors.lastname: Michaud
authors.forename: Lionel
authors.initials: L
authors.lastname: Carmant
mesh_terms: D000293:Adolescent; D000328:Adult; D002540:Cerebral Cortex / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D054091:Periventricular Nodular Heterotopia / Q000209:etiology / Q000401:mortality / Q000473:pathology*; D055815:Young Adult