Olfactory dysgenesis or hypoplasia

Abstract

Postmortem examination of a 65-year-old anosmic woman revealed rudimentary olfactory bulbs, an imperforate cribriform plate, and sulcal abnormalities of the orbitofrontal surface of the brain. The remainder of the brain, skull, and body was normal. This abnormality most likely resulted from a local insult to the area of the cribriform plate during early fetal life, occurring after the induction of olfactory bulb differentiation, but before migration and complete differentiation of the olfactory bulbs. Such a lesion can be dated to approximately 11 to 12 weeks gestational age. The malformation may represent another variant in the arhinencephaly spectrum, but is termed "olfactory dysgenesis" or "olfactory hypoplasia" to separate it from true olfactory aplasia and arhinencephaly.

International consensus statement on allergy and rhinology: Olfaction

“…912 Characteristic MRI findings include underdevelopment of the OB or sulcus, an imperforate cribriform plate, and/or distinct changes in the volume of cortical regions associated with olfactory memory. 540,[917][918][919][920] Biopsies may yield respiratory rather than OE findings. 921 Genetic factors likely play some role and family clusters have been identified with CNGA2 and TENMI1 mutations on whole exome sequencing.…”

“…Associations have been noted between anosmia and CHARGE syndrome, with CHD7 and other gene mutations identified on gene sequencing 995,998 . Congenital insensitivity to pain is associated with hyposmia through a SCN9A mutation 999 . Syndromic ciliopathies, such as Bardet‐Biedl, have also been associated with congenital hyposmia from basic research on mechanisms 1000,1001 and by a match‐controlled study 1002 .…”

Isolated and syndromic forms of congenital anosmia

“…The anosmia in these cases might be explained by non‐functional OE as indicated by biopsies taken from the Danish women, where only respiratory epithelium was present (12). The presence of an imperforate cribiform plate has been reported by autopsy in one woman with ICA, who also presented with rudimentary OB and diminished olfactory sulcus depth (19). Autopsy of another woman with self‐reported ICA revealed the absence of OB and tracts (22).…”

“…This is most often undocumented and based on patient recollection (12–15). Other studies report cases with no family history of anosmia (16–19), or where information regarding family history is not present (20–22). ICA families tend to display an autosomal dominant inheritance pattern with reduced penetrance (10–12, 23–26). Whether this reflects the bias of dominant families being easier to find or the genetic nature of ICA is unknown.…”

“…This is most often undocumented and based on patient recollection (12)(13)(14)(15). Other studies report cases with no family history of anosmia (16)(17)(18)(19), or where information regarding family history is not present (20)(21)(22). ICA families tend to display an autosomal dominant inheritance pattern with reduced penetrance (10)(11)(12)(23)(24)(25)(26).…”