Imaging of Clival Hypoplasia in CHARGE Syndrome and Hypothesis for Development: A Case-Control Study

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Fig 1.
Clival abnormalities in CHARGE syndrome. A, Sagittal T1 scan of a 4.5-year-old boy without CHARGE syndrome. White lines show the measurement of the Ba-Es and Ba-Xs. B, A 22-month-old boy with CHARGE syndrome (patient 14). He has a hypoplastic sclerotome of the clivus (arrow) with a large Welcher angle. Although the top of the odontoid process of the dens does not extend cranially to the Chamberlain line, there is a slight angulation of the medulla oblongata without impression. C and D, Clival size versus age. White dots show length of the Ba-Es (C) and Ba-Xs (D) of the individual controls; black dots show the same parameters of individual patients with CHARGE syndrome.
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Fig 2.
Platybasia in patients with CHARGE syndrome. A, Sagittal T1 scan of a 4.5-year-old boy without CHARGE syndrome. The Welcher line is shown in white. B, A 22-month-old boy with CHARGE syndrome (patient 14). Note the large Welcher angle on the midsagittal T1 scan. C, Welcher angle versus age. White dots show the Welcher angle of the individual controls. Black dots show the Welcher angles of individual patients with CHARGE syndrome.

Table 1:

Characteristics for 23 patients with CHARGE syndrome in our case series

Characteristics
Median age (range)	20 Mo (3 days to 16 yr)
Males	15
Females	8
Criteria of Blake et al⁵ satisfied^{^a}
Typical CHARGE syndrome	12
Negative	8
Missing data	3
Criteria of Verloes⁶ satisfied^{^a}
Typical CHARGE syndrome	12
Partial CHARGE syndrome	0
Atypical CHARGE syndrome	5
Negative	0
Missing data	6
Criteria of Hale et al⁷ criteria satisfied^{^a}	23
Mutation type (n = 23)^{^b}
Truncating (nonsense, frameshift, deletion)	17
Nontruncating (missense)	2
Splice site	4

↵a See On-line Table 1.
↵b Truncating mutations (nonsense or frameshift) lead to a decrease in CHD7 protein. Nontruncating (missense) mutations lead to production of an altered CHD7 protein, which may have residual function. Splice site mutations may have truncating or nontruncating effects.

Table 2:

Correlations between clivus size and clinical parameters

Variable	Size of Clivus		P Value
Variable	Normal	<2.5 SDs Compared with Controls	P Value
Truncating mutation (total n = 19)^{^a}
+	5	12	.12
−	2	0	.12
Presence of choanal atresia
+	1	4	.33
−	8	10	.33
Presence of coloboma (total n = 22)^{^b}
+	4	8	.36
−	5	5	.36
Presence of cleft (total n = 22)^{^b}
+	3	2	.61
−	6	11	.61
Verloes⁶ criteria satisfied^{^c}
+	4	8	1.00
−	2	3	1.00
Blake et al⁵ criteria satisfied^{^c}
+	3	5	1.00
−	4	8	1.00

Note:—+ indicates yes; −, no.
↵a Four patients had a splice site mutation and could not be classified as either truncating or nontruncating.
↵b For 1 patient, no data regarding presence of coloboma were available. For 1 patient, no information regarding cleft lip/palate was available.
↵c See also On-line Table 1.