Kuhlenbaumer et al. (2004) reported a large German family in which 8 members spanning 3 generations had basal ganglia disease inherited in an autosomal dominant pattern. Family history suggested 5 affected members in previous generations. The proband presented ... Kuhlenbaumer et al. (2004) reported a large German family in which 8 members spanning 3 generations had basal ganglia disease inherited in an autosomal dominant pattern. Family history suggested 5 affected members in previous generations. The proband presented at age 38 years with mild slurring of speech and 'stiffness' in her tongue. The dysarthria progressed, and the patient later developed gait disturbance, mild bradykinesia, dysdiadochokinesia, and brisk lower extremity reflexes. Tremor was not present and the symptoms did not respond to levodopa treatment, thus clearly distinguishing the disorder from Parkinson disease (168600). Other affected family members had similar symptoms with onset in the fourth or fifth decade, but the exact age at onset could not be determined because of the insidious onset and slow progression of the disorder. Cranial MRI studies showed characteristic symmetric abnormalities of the basal ganglia, primarily a signal increase on T2-weighted images and a corresponding signal decrease on T1-weighted images. Lesions appeared to start in the dorsal putamen and later involved the caudate. Large lesions showed a slight mass effect. Kuhlenbaumer et al. (2004) noted that the disorder in this family, which they termed 'autosomal dominant striatal degeneration (ADSD),' showed some similarities to adult-onset basal ganglia disease (606159), which is caused by mutation in the ferritin light chain gene (FTL; 134790) on chromosome 19q13. However, that disease is characterized by hyperkinesia, whereas ADSD shows hypokinesia.
In affected members of the family with adult-onset autosomal dominant striatal degeneration reported by Kuhlenbaumer et al. (2004), Appenzeller et al. (2010) identified a heterozygous mutation in the PDE8B gene (603390.0002), resulting in a loss of protein function. ... In affected members of the family with adult-onset autosomal dominant striatal degeneration reported by Kuhlenbaumer et al. (2004), Appenzeller et al. (2010) identified a heterozygous mutation in the PDE8B gene (603390.0002), resulting in a loss of protein function.