Early-onset Parkinson’s Disease Associated with Chromosome 22q11.2 Deletion Syndrome

Figure. (A) T2-weighted brain MRI showing cavum vergae. (B) 123I-FP-CIT-SPECT revealed a re- duced uptake in both of the putamen, which was more prominent on the right. (C) 123I-metaiodoben- zylguanidine scintigraphy showing normal cardiac uptake in the early and delayed phases. (D) A FISH chromosome analysis indicating del(22) (q11.2q11.2)(TUPLE1-). 

February 7, 2016
Abstract

We herein report the case of a 43-year-old man with a 4-year history of resting tremor and akinesia. His resting tremor and rigidity were more prominent on the left side. He also presented retropulsion. His symp- toms responded to the administration of levodopa. The patient also had a cleft lip and palate, cavum vergae, and hypoparathyroidism. A chromosome analysis disclosed a hemizygous deletion in 22q11.2, and he was di- agnosed with early-onset Parkinson’s disease associated with 22q11.2 deletion syndrome. However, the patient lacked autonomic nerve dysfunction, and his cardiac uptake of 123I-metaiodobenzylguanidine was nor- mal, indicating an underlying pathological mechanism that differed to that of sporadic Parkinson’s disease.

Introduction

Chromosome 22q11.2 deletion syndrome (22q11.2DS) is the second most common chromosomal abnormality next to Down’s syndrome. It causes abnormalities in the midline structures such as characteristic facial features, cleft lip and palate, hypoparathyroidism, and cavum vergae. It also causes mental retardation or schizophrenia (1).

Several cases of early-onset Parkinson’s disease (PD) as- sociated with 22q11.2DS have been reported, but its patho- logical mechanism is not yet clear. We herein report a case of early-onset PD associated with 22q11.2DS, review the previous cases in the literature, and discuss the possible pathogenesis. 

Case Report 

A 43-year-old man presented with resting tremor, dis- abling akinesia, and gait disturbance. He first noticed a rest- ing tremor in his left arm at 39 years of age, for which a nearby neurologist prescribed pramipexole (0.5 mg tid). His tremor was not relieved, and the medication was discontinued. Short-stepped gait and bradykinesia developed at 41 years of age. He became depressed at 42 years of age, but improved spontaneously over the following 3 months. How- ever, the motor symptoms showed gradual progression, and he eventually required help in getting dressed.

He received an operation for a cleft lip and palate in his infancy. Hypocalcemia was diagnosed when he was 39 years of age, and 1-alpha-calcidol was prescribed. Neither neuro- logical diseases nor consanguinity were reported in his fam- ily history. On examination, he was alert and did not show signs of dementia. Although he was not aware of anosmia, his odor identification rate in the Odor Stick Identification Test for Japanese (2) was 25%, indicating decreased olfac- tory recognition ability. His facial expression was mask-like, and his speech was monotonous. The patient’s rigidity was severe in the neck, moderate on the left side and mild in the right extremities. A pill-rolling tremor of 4-6 Hz was no- ticed predominantly on the left side. Finger- and foot- tapping was decreased predominantly on the left side. His gait was short-stepped, but independent. Retropulsion was noticed. Orthostatic hypotension was not observed in the head-up tilt test. Constipation was denied. No symptoms of rapid eye movement (REM) sleep behavior disorder (RBD)were detected on the RBD screening questionnaire.

The results of an electrocardiogram, chest X-ray, and rou- tine blood tests were normal. Brain CT and MRI (Figure A) studies showed cavum vergae, but no calcification was de- tected. The patient’s total Unified Parkinson’s Disease Rat- ing Scale (UPDRS) part III score improved by 28% after the intravenous infusion of 100 mg levodopa. The ioflupane (123I)-FP-CIT-single photon emission computed tomography (SPECT) (Figure B) showed the reduced uptake of both of the putamen (specific binding ratio: R/L=1.81/2.28). The heart to mediastinum (H/M) ratio obtained by 123I- metaiodobenzylguanidine (MIBG) cardiac scintigraphy (Fig- ure C) was 2.29 in the early phase and 2.60 in the late phase. A fluorescence in situ hybridization (FISH) chromo- some study (Figure D) disclosed del(22) (q11.2q11.2) (TUPLE1-), and a genetic analysis revealed no mutations in the Parkin, PINK1, LRRK2 or SYNA genes. 
Mitsuaki Oki, Shin-ichiro Hori, Shinya Asayama, Reika Wate, Satoshi Kaneko and Hirofumi Lusaka

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http://www.topix.com/health/parkinsons-disease/2016/02/early-onset-parkinsons-disease-associated-with-chromosome-22q11-2-deletion-syndrome