Page 44 - Characterization of genetic neurodevelopmental disorders at adult age, with a focus on 22q11.2 deletion syndrome - Emma Boersma

Chapter 2
Neuropathology
Neuropathological findings were reported for 16 patients (11 male;
73.3%) at median age 57 (range 2-74) years: 22q11.2 deletion syndrome
(n=3), Down syndrome (n=2), POLG (n=2), BPAN (n=1), CTX (n=1), Cornelia
de Lange syndrome (n=1), DNAJC12 (n=1), DOORS syndrome (n=1),
5,10-methylenetetrahydrofolate reductase deficiency (n=1), NR4A2 (n=1),
PPP2R5D (n=1) and RAB39B (n=1) (Table 2). In 14 patients, the presence
of Lewy bodies was examined, with positive findings in six cases (42.9%):
22q11.2 deletion syndrome (n=2/3), Down syndrome (n=2/2), NR4A2 (n=1/1)
and RAB39B (n=1/1). Neurites were examined in nine patients and present
in seven: 22q11.2 deletion syndrome (n=2/3), Cornelia de Lange syndrome
(n=1/1), DNAJC12 (n=1/1), Down syndrome (n=1/1), NR4A2 (n=1/1) and
RAB39B (n=1/1). Neuronal loss was reported in all but one patient (92.9%),
the latter who had DOORS syndrome.
Table 2. Neuropathological findings in patients with genetic neurodevelopmental disorders and
parkinsonism
Genetic neurodevelopmental disorder Age, y Sex LB LN Neuronal loss
22q11.2 deletion syndrome 82 F
M
M
BPAN 83 CTX 69 Cornelia de Lange syndrome 84 DNAJC12 85 DOORS syndrome 37 Down syndrome 86, 87 MTHFR deficiency 88 +
+
-
F - M NR M - M - M - +
+
NR -
-
M + +
+
-
M
M
+
+
+
NR +
NR +
+ * +
+ * +
NR -
+
+
NR +
+ + +
+
+
+ +
+ *
NR
56
58
61
27 56 38 74 72 54
49
74 61
60
61 48 2 F Abbreviations: y = years, LB = Lewy bodies, LN = Lewy neurites, F = female, M = male, + = present,
- = absent,
BPAN = Beta-propeller protein associated neurodegeneration, NR = not reported, + * = neurites
(unspecified), CTX
=
cerebrotendinous xanthomatosis, MTHFR
=
5,10-methylenetetrahydrofolate
reductase.
NR4A2 89 NR POLG 90 F
M
-
-
PPP2R5D 91 M - - +
RAB39B 92 42