A 14-month-old Hispanic female with a history of double-outlet right ventricle and developmental delay in the setting of recombinant chromosome 8 syndrome was referred for neurologic imaging. Brain MR revealed multiple abnormalities primarily affecting midline structures, including commissural dysgenesis, vermian and brainstem hypoplasia/dysplasia, an interhypothalamic adhesion, and an epidermoid between the frontal lobes that enlarged over time. Spine MR demonstrated hypoplastic C1 and C2 posterior elements, scoliosis, and a borderline low conus medullaris position. Presented herein is the first illustration of neuroimaging findings from a patient with San Luis Valley syndrome.
San Luis Valley syndrome (SLVS) is a rare chromosomal inversion disorder that prevalently affects individuals of Hispanic origin. The name is derived from a presumed founder effect traced to the San Luis Valley in the southwestern United States. SLVS is caused by deletion of the terminal part of the short arm of chromosome 8 (8pter-p23.1) together with duplication of the terminal part of the long arm of chromosome 8 (8q22.1-qter) [
Characteristic features of SLVS include facial dysmorphia, congenital heart disease, and genitourinary abnormalities [
A neonatal Hispanic female was referred to the department of genetics for evaluation of facial dysmorphism, congenital heart disease, and a two-vessel umbilical cord suggestive of an underlying syndrome. She was the product of an uncomplicated pregnancy, born at term. Karyotype analysis was compatible with San Luis Valley syndrome (46, XX, Rec (8) Dup (8Q) Inv (8) p23.1 q22.1). Past medical history was notable for complex cardiac deformities including double-outlet right ventricle, ventricular septal defect, subvalvular pulmonic stenosis, pulmonary arterial hyperplasia, restrictive cardiomyopathy, and an aberrant retroesophageal right subclavian artery. The patient had previously undergone cardiac surgery for tunnel repair and infundibular resection. She had facial dysmorphism typifying the San Luis Valley syndrome including hypertelorism, frontal bossing, wide-spaced teeth, elevated palate, and down-turned corners of the mouth. She also had nystagmus, astigmatism, intermittent esotropia, and refractive errors. However, external, anterior, retinal, and dilated fundoscopic exams were normal. At 14 months of age, she was referred to our imaging service to have a brain MRI for developmental delay.
The initial brain MR revealed multiple midline abnormalities including corpus callosum dysgenesis, anterior commissure hypoplasia, an interhypothalamic adhesion, and brainstem and vermian hypoplasia/dysplasia (Figures
Sagittal SPGR T1WI (repetition time msec/echo time msec/inversion time msec, 13/5/500) showing multiple midline brain abnormalities including a thin corpus callosum, brainstem hypoplasia, vermian hypoplasia (black arrow), and a subtle interhypothalamic adhesion (small white arrow). There is also vertebrobasilar ectasia, abutting and deforming the basis pontis (large white arrow).
Coronal T2WI (repetition time msec/echo time msec, 2767/102) depicting a horizontally oriented band of tissue connecting the hypothalami to one another, an interhypothalamic adhesion (small arrows). The basilar artery is tortuous and ectatic (large arrow).
Axial T2-weighted fast spin echo image (repetition time msec/echo time msec, 6083/108) demonstrating irregular cerebellar fissuration/foliation consistent with dysplasia (large arrows), enlarged inner ear vestibules representing dysplasia (small arrows), and malformation of the medulla oblongata with underdevelopment of the median sulcus and absent preolivary sulci (arrowhead). The vermis is not present on this transaxial section as it should be, consistent with vermian hypoplasia.
Axial T2 FLAIR image (repetition time msec/echo time msec/inversion time msec, 10002/135/2200) through the lateral ventricles depicting deep/paraventricular white matter hyperintensity consistent with gliosis from old injury (arrows). Diminished cerebral white matter volume is present with decreased white matter depth and mild ventriculomegaly.
At 5 years, she developed seizures with episodes leading to apnea, desaturations, and bradycardia. Repeat brain MR demonstrated, in addition to the previously seen midline defects, an epidermoid cyst interposing the frontal lobes in the anterior interhemispheric region (Figures
Sagittal SPGR T1WI (repetition time msec/echo time msec/inversion time msec, 13/5/500) redemonstrating multiple midline brain abnormalities including a thin, dysgenetic corpus callosum, brainstem hypoplasia, vermian hypoplasia (black arrow), and an interhypothalamic adhesion (small white arrow). A newly visible extra-axial hypointense structure is centered in the anterior cingulate sulci representing an epidermoid (white arrowhead). Vertebrobasilar ectasia is again shown, abutting and deforming the basis pontis (large white arrow). Normal C1 and C2 posterior elements are not identified on this midline sagittal image, consistent with hypoplasia (black arrowhead).
Axial diffusion weighted image (repetition time msec/echo time msec, 10000/82;
Maximum intensity projection image from a 3D time-of-flight MR angiogram of the vertebrobasilar system displayed in the coronal plane (repetition time msec/echo time msec, 21/2) demonstrating vertebrobasilar dolichoectasia (large arrow) and duplication of the superior cerebellar arteries (small arrows).
Currently at 7 years, the patient has medically refractory severe complex partial epilepsy. Her language and motor skill developmental milestones are markedly delayed. She has hyperopia and nystagmus. Eustachian tube dysfunction has led to intermittent middle ear infections. She ultimately underwent percutanous nephrostomy for lithotripsy. The most recent brain MRI failed to demonstrate any significant interval change.
San Luis Valley syndrome is a genetic disease caused by a recombinant chromosome 8 pericentric inversion [
Brain abnormalities in patients with SLVS Rec(8) and duplication 8q.
Author |
|
Defect | Method of analysis | Midline defects | BS | CB | Cephalocele | CSF spaces | Myelin | WM lesions | V |
---|---|---|---|---|---|---|---|---|---|---|---|
Whitehead |
1 | Rec(8)a | MR | CCD |
Yes | Yes | No | VM |
WNL | Yes | Yes |
|
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Sujansky et al. [ |
15 |
Rec(8)a | CT/US |
CCD |
NM | NM | No | VM (13/15) |
Delay (4/4) | NM | NM |
|
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Vera-Carbonell et al. [ |
1 | Rec(8)b | MR | NM | NM | NM | NM | VM | NM | NM | NM |
|
|||||||||||
Williams et al. [ |
9 | Rec(8)a |
Path | CCT |
Yes |
NM | Yes |
Hydro |
NM | Yes |
NM |
|
|||||||||||
Nucaro et al. [ |
1 | Rec(8)d | MR | NM | NM | NM | NM | NM | NM | PVL | NM |
|
|||||||||||
Wheeler [ |
1 | Dup(8)a | US | WNL | No | No | No | WNL | NA | No | NA |
|
|||||||||||
Concolino et al. [ |
1 | Dup(8)b | MR | NM | NM | NM | Yes |
NM | NM | NM | NM |
Rec(8)a = Rec(8)dup(8q)inv(8)(p23.1q22.1);
Rec(8)b = Rec(8)dup(8q)inv(8)(p23.2q22.3)mat.ish rec(8)(wcp8þ).mlpa 8psubtel(P036) × 1,8qsubtel(P036) × 3.arr 8p23.3p23.2(1–2,274,223) × 1,8q22.3q24.3(104,430,376–146,364,022) × 3;
Rec(8)c = Rec(8)dup(8q)inv(8)(p23q23);
Rec(8)d = InvDupDel 8p(dup 8p22–p23.1/del 8p23.2-pter);
Dup(8)a = Dup (8)(q23.3q24.21);
Dup(8)b = Dup (8)(q22.2–24.3)(q24.21), 8q22.2 (RP11-102K7 clone-101.2Mb) to 8q24.3 (RP11-120B22 clone-144.3Mb);
U = unknown or unconfirmed.
Our patient had multiple central nervous system abnormalities predominantly affecting midline structures. Specifically, commissural white matter fibers traversing the corpus callosum and anterior commissure were hypoplastic and the corpus callosum was dysmorphic consistent with corpus callosum dysgenesis. An interhypothalamic adhesion was present, a marker for defective midline brain formation and potentially a form fruste holoprosencephaly [
MR images from our patient also exhibited bilateral vestibular dysplasia. The inner ear vestibules house the utricles and saccules that influence the sensation of balance equilibrium. Structural and/or functional vestibular abnormalities have not been previously described to the best of our knowledge. The majority of SLVS patients have conductive and/or sensorineural hearing loss [
We also noted mild bilateral microphthalmia in our patient. The globes were symmetrically small in the anteroposterior dimensions. This may account for the patient’s hyperopia. Ophthalmologic abnormalities have been found in a majority of patients with San Luis Valley syndrome [
The intracranial arterial flow voids were mildly tortuous and ectatic in our patient. There was notable dolichoectasia of the basilar artery causing mass effect on the basis pontis. Numerous cerebral white matter lesions were consistent with gliosis from prior injury. A few cerebral and cerebellar old microhemorrhages were also present. The cerebral white matter volume was decreased. Collectively, these findings were most likely related to complications of congenital heart disease and treatment. It is unclear to what extent the underlying genetic defect may have predisposed or contributed to these changes. Though occasionally seen as a normal variation, duplication of the superior cerebellar arteries and right anterior cerebral artery A1 segment could indicate an underlying intracranial vascular tree malformation in concert with the more generalized arterial tortuosity, arterial ectasia, and congenital heart disease.
Concerning the spine, we found hypoplasia of the C1 and C2 posterior elements, an L6 vertebral body, mild scoliosis, paraspinal muscular atrophy, and borderline low termination of the conus medullaris. There were no documented symptoms of tethered spinal cord syndrome. There are no previous studies with cross-sectional imaging correlation demonstrating spinal abnormalities in patients with San Luis Valley syndrome. However, Sujansky and colleagues reported what was described as a noncongenital progressive neuromuscular scoliosis in 13 of 20 SLVS patients that underwent spine radiography [
We present neuroimaging abnormalities associated with San Luis Valley syndrome. Multiple midline anomalies including commissural dysgenesis, interhypothalamic adhesion, epidermoid cyst, and brainstem and cerebellar dysgenesis/hypogenesis were the most striking features.
The authors declare that there is no conflict of interests regarding the publication of this paper.