Kallmann Syndrome

Epidemiology and Etiology:

· Mutations (20-25%)

· KAL1 (Xp22.3) (X-linked recessive)

· Anosmin-1

· Impaired function causes a migratory defect of the olfactory and GnRH neurons from the olfactory placode during development

· FGFR1 (8p11.2 to 8p11.1) (autosomal dominant)

· Basic fibroblast growth factor receptor 1

· PROKR2 (20p13 ) (autosomal dominant)

· Prokineticin receptor 2

· PROK2 (3p21.1 ) (autosomal dominant)

· Prokineticin-2

· Deletions

· KAL1 (extremely rare)

Common sites:

·

Gross features:

· isolated hypogonadotropic hypogonadism (IHH)

· micropenis

· cryptorchidism

· incomplete sexual maturation in adolescence

· absent facial and axillary hair growth

· absent voice deepening

· little or no breast development

· pre-pubertal testicular volume in adulthood (< 4 mL)

· increased muscle mass

· eunuchoidal body habitus

· arm-span exceeding height by 5cm or more

· olfactory bulb malformation detectable by MRI in majority of individuals

· agenesis of corpus collossum maybe

· synkinesia of the digits maybe

· brachydactyly maybe

· syndactyly maybe

· unilateral renal agenesis maybe

· cleft lip or palate maybe

· agenesis of one or more teeth maybe

Histologic features:

·

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

·

Other features:

· isolated hypogonadotropic hypogonadism (IHH)

· anosmia (may or may not be aware)

· diminished libido

· erectile dysfunction

· infertility

· primary amennhorea in females

· sensorineural hearing loss maybe

· low or normal LH and FSH in the setting of low sex steroid concentrations and normal pituitary and hypothalamus on MRI

· absence of other hypothalamic or pituitary abnormalities

References:

· Kallmann Syndrome -- GeneReviews -- NCBI Bookshelf. Available at: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=kms [Accessed June 13, 2009].