A Case of Kallmann Syndrome Associated with Dandy-Walker Malformation

Abstract

A 19-year-old man was admitted to our hospital for delayed puberty. At birth, he had macrocephalia and showed delayed physical and mental development. At 9 years of age, right cryptorchism was diagnosed. His parents had noticed that he could not recognize any smells since his infancy. Physical examination on admission revealed ocular hypertelorism, high myopia, high arched palate, and intermittent external strabismus. Sense of smell was scaled out by olfactometry. External genitalia were infantile. Neurological examination showed on IQ of 83, and mild truncal ataxia. Magnetic resonance imaging (MRI) showed a cystic distension of the IV ventricle, partial aplasia of the cerebellar vermis, elevation of the tentorium cerebelli, enlargement of the III ventricle, and agenesis of the corpus callosum. These findings revealed that the patient had Dandy-Walker malformation. The basal FSH, LH, and testosterone levels were all low compared with normal adult reference values. The serial LH-RH provocation tests showed stepwise LH and FSH elevation. After the fifth day of LH-RH administration, both LH and FSH responses clearly improved. Olfactory tracts were defective in MRI findings. These findings were consistent with hypogonadotropic hypogonadism of hypothalamic origin with anosmia, and the patient was therefore diagnosed with Kallmann syndrome. Sequence analysis of the KAL1 gene showed no mutation in the coding region. To our knowledge, this is the first case report of the coexistence of Kallmann syndrome and Dandy-Walker malformation in the same patient.

Ataxia and focal dystonia in Kallmann syndrome

“…Abnormal or absent olfactory bulbs and tracts in KS can be detected with neuroimaging studies , as in our case; other anomalies of the CNS that may also be present in KS are agenesis of the corpus callosum and Dandy–Walker malformation .…”

Neural Crest and Ectodermal Cells Intermix in the Nasal Placode to Give Rise to GnRH-1 Neurons, Sensory Neurons, and Olfactory Ensheathing Cells

“…In humans, the pathology associated with defects in olfactory system development and impaired migration of GnRH-1 neurons is called Kallmann syndrome (Wray, 2010) and characterized by anosmia (lack of smell) and lack of pubertal onset (Sykiotis et al, 2010). The Kallmann phenotype can be associated with other syndromic diseases such as CHARGE syndrome (Ogata et al, 2006) and can display neural crest (NC) associated defects involving craniofacial dysmorphisms, cleft palate, dental agenesis, synkinesis, lack of mirror movements, deafness, ocular albinism, cerebellar defects and dementia (Krams et al, 1997; Molsted et al, 1997; Ueno et al, 2004; Hou, 2005; Zenaty et al, 2006; Bhagavath and Layman, 2007). However, localization and lineage of GnRH-1 progenitors is still unclear.…”

Brain Changes in Kallmann Syndrome

“…[7][8][9][10][11][12][13] This sulcal abnormality is thought to be driven by the absence/hypoplasia of the olfactory bulbs and represents an intriguing model of genetically driven developmental brain abnormalities. Furthermore, a few case reports postulated the strict relationship between KS and midline brain abnormalities, such as corpus callosum agenesis and holoprosencephaly, 6,16 though pathologic and neuroimaging data are relatively scarce and often contradictory. 7 In 2008, a pioneering study by voxel-based morphometry (VBM) MR imaging analysis revealed distinct regional gray and white matter volume changes in male patients with KS outside the frontal orbital regions.…”