Neuropathologic findings in a case of OFDS type VI (V�radi syndrome)

Abstract

Oral-facial-digital syndrome type VI (OFDS VI) or Váradi syndrome is a rare autosomal-recessive disorder distinguished from other oral-facial-digital syndromes by metacarpal abnormalities with central polydactyly and by cerebellar abnormalities. Histopathologic characterization of the cerebellar abnormalities has not been described previously. We describe the neuropathologic findings in a stillborn, 21-week estimated gestational age (EGA) male fetus diagnosed antenatally with signs of OFDS VI. Autopsy findings included: facial abnormalities, postaxial central polydactyly of the right hand, bilateral bifid toes, and absence of cerebellar vermis with hypoplasia of the hemispheric cortex. Microscopic analysis of the cerebellum demonstrated absence of the subpial granular cell layer and disruption or dysgenesis of the glial architecture. These histopathologic findings suggest that a primary neuronal or glial cell defect, rather than an associated Dandy-Walker malformation, may account for the cerebellar abnormalities in this form of oral-facial-digital syndrome.

An autopsy case of an infant with Joubert syndrome who died unexpectedly and a review of the literature

“…Autopsy demonstrated partial hypoplasia of the cerebellar vermis, and no other neurological or physical anomaly. These findings suggest a relatively mild anomaly of the cerebellar vermis, compared with previous cases [6].…”

“…About 10% of the patients died on the day of birth, and about 30% died within 1 year after birth [46,47]. Early death in infancy was mainly related to complete aplasia of the cerebellar vermis and/or severe neurological complications [6]. However, deaths were directly caused by infection involving pneumonia and meningitis possibly as a consequence of latent aspiration or complicated infection [5,[48][49][50].…”

“…Some cases also possessed anomaly of the brainstem [6,7]. Other commonly found central nervous system abnormalities extending beyond the cerebellum have also described, including a cortical atrophy, delayed myelination, and an enlarged fourth ventricle [8].…”

Prenatal diagnosis of oral-facial-digital syndrome, type I.

“…OFD syndrome, type VI (Varadi syndrome), was described in a 19 week female fetus with a small cerebellar vermis and right hand polydactyly. 9 The sonographic antenatal identification of polydactyly and a heart defect in a family with no history of malformations suggested features of both types II and VI OFD syndromes. 10 OFD syndrome, type I, has been reported postnatally.…”

Oral–Facial–Digital Syndrome type VI with self mutilations

“…Oral-Facial-Digital Syndrome type VI (OFD6) is a rare autosomal recessive disorder distinguished from other OralFacial-Digital Syndromes by metacarpal abnormalities with central polydactyly and by cerebellar abnormalities [16].…”