Pontine tegmental cap dysplasia: a novel brain malformation with a defect in axonal guidance.
Four unrelated children are described with an identical brainstem and cerebellar malformation on MRI. The key findings are: vermal hypoplasia, subtotal absence of middle cerebellar peduncles, flattened ventral pons, vaulted pontine tegmentum, molar tooth aspect of the pontomesencephalic junction and absent inferior olivary prominence. Peripheral hearing impairment is present in all. Variable findings are: horizontal gaze palsy (1/4), impaired swallowing (2/4), facial palsy (3/4), bilateral sensory trigeminal nerve involvement (1/4), ataxia (2/4). Bony vertebral anomalies are found in 3/4. Additional MR studies in one patient using diffusion tensor imaging (DTI) with colour coding and fibre tracking revealed an ectopic transverse fibre bundle at the site of the pontine tegmentum and complete absence of transverse fibres in the ventral pons. The combined findings indicate an embryonic defect in axonal growth and guidance. Phenotypic analogy to mice with homozygous inactivation of Ntn1 encoding the secreted axonal guidance protein netrin1, or Dcc encoding its receptor Deleted in Colorectal Cancer led us to perform sequence analysis of NTN1 and DCC in all the patients. No pathogenic mutations were found. For the purpose of description the name 'pontine tegmental cap dysplasia' (PTCD) is proposed for the present malformation, referring to its most distinguishing feature on routine MRI.
Barth
Peter G
PG
Department of Pediatric Neurology, Emma Children's Hospital/AMC, University of Amsterdam, Amsterdam, Netherlands.
Majoie
Charles B
CB
Caan
Matthan W A
MW
Weterman
Marian A J
MA
Kyllerman
Marten
M
Smit
Leo M E
LM
Kaplan
Richard A
RA
Haas
Richard H
RH
Baas
Frank
F
Cobben
Jan-Maarten
JM
Poll-The
Bwee Tien
BT
D001369:Axons / Q000473:pathology*; D001921:Brain / Q000473:pathology; D002531:Cerebellum / Q000002:abnormalities* / Q000473:pathology; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005260:Female; D016163:Genes, DCC / Q000235:genetics; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D009414:Nerve Growth Factors / Q000235:genetics; D000075388:Netrin-1; D011149:Pons / Q000002:abnormalities* / Q000473:pathology; D013577:Syndrome; D025521:Tumor Suppressor Proteins / Q000235:genetics
C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1