Isolated congenital anosmia with morphologically normal olfactory bulb in two Iranian families: A new clinical entity?

Abstract

Congenital total loss of the sense of smell occurs as a part of a syndrome or isolated anosmia. Kallmann syndrome is the most well known congenital anosmia associated with hypogonadotropic hypogonadism. Isolated congenital anosmia (ICA) is a very rare condition and appears to be due to changes in the olfactory epithelium or to aplasia of the olfactory nerve, bulb, and tract. Here we report two unrelated Iranian families with ICA. One family consisted of nine affected members, and the other family contained three affected members. Clinical history, physical examination, and smell testing by intravenous injection of combined vitamins (Alinamin trade mark, Takeda Pharmaceutical Co. Ltd., Japan) confirmed the disease in each affected member. No signs of hypogonadism or other neurological disorders were observed in any affected members. Family analysis with the complete ascertainment method under assumption of the same condition in the two families suggested that the disease is not inconsistent with an autosomal dominant mode with incomplete penetrance. The inheritance in one family appears unusual, i.e., there were no affected individuals in the third generation. When only two upper generations in the family are concerned, the segregation ratio was 0.39 +/- 0.11. Male-to-male transmissions were observed and both sexes were affected in both families. Magnetic resonance imaging (MRI) of the olfactory bulb and sulcus revealed no evidence of morphological changes in all affected members, suggesting that these patients have either a defect in the olfactory epithelium or a functional defect in the olfactory cortex.

PROKR2 and PROK2 mutations cause isolated congenital anosmia without gonadotropic deficiency

“…ICA may be due to developmental abnormalities such as olfactory bulb agenesis. It may also occur in the absence of developmental defect, possibly as a result of deficient intracellular signaling in the olfactory receptor pathway (2,3,4).…”

“…Most ICA cases are sporadic, but familial cases with dominant and reduced penetrance have been reported (3,4). The mode of transmission of syndromic CA is mainly determined by that of the underlying syndrome.…”

“…The mode of transmission of syndromic CA is mainly determined by that of the underlying syndrome. Genome mapping performed in two ICA Iranian familial cases with autosomal transmission and incomplete penetrance led to the mapping of a candidate region on chromosome 18 (4,6). Recently, screening of three genes encoding the three major transduction components of primary sensory neurons failed to identify causative mutations in patients with ICA (3).…”

Isolated congenital anosmia locus maps to 18p11.23-q12.2

“…To our knowledge, nine sporadic cases of isolated congenital anosmia have been known, 1 2 and patients reported by Lygonis 3 and those by us 4 were only familial isolated congenital anosmia. Other cases of familial congenital anosmia had some additional manifestations [5][6][7][8][9] or had Kallmann syndrome.…”

Pathology of the Olfactory Nerve

“…Today the diagnosis of isolated congenital anosmia or Kallmann's syndrome centers on MRI. 1,9,[16][17][18][19][20][21][22][23][24][25] In addition, assessment of OB volume is applied in subjects who have CHARGE syndrome [26][27][28] where the olfactory system is compromised. Oblique sagittal multiplanar reformation of a strongly T2-weighted CISS sequence in a patient who had anosmia.…”