Vici Syndrome: A Rare Autosomal Recessive Syndrome with Brain Anomalies, Cardiomyopathy, and Severe Intellectual Disability

Abstract

Purpose. The objective of this study was to present and describe two additional patients diagnosed with Vici syndrome. Methods. Clinical, laboratory, and imaging findings of the two siblings are discussed in detail. The two patients' descriptions are compared with the other eleven patients reported in the literature. We also presented detailed autopsy results on the male sibling, which demonstrated cytoplasmic vacuoles of the cardiomyocytes and confirmed the clinical findings. Results. The patients reported here include the 13th and 14th patients reported with Vici syndrome. The summary of findings present in these patients includes postnatal growth retardation, developmental delay, bilateral cataracts, agenesis of the corpus callosum, cerebellar anomalies, gyral abnormalities, seizures, hypotonia, and cardiomyopathy. Conclusion. Vici syndrome should be suspected in any child with agenesis of the corpus callosum and one of the following findings: cardiomyopathy, cataracts, immune deficiency, or cutaneous hypopigmentation.

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Hindawi Publishing Corporation
Case Reports in Genetics
Volume 2011, Article ID 421582, 4pages
doi:10.1155/2011/421582
Case Report
Vici Syndrome: A Rare Autosomal Recessive Syndrome with Brain
Anomalies, Cardiomyopathy, and Severe Intellectual Disability
R. Curtis Rogers, Bridgette Aufmuth, and Stephanie Monesson
Greenwood Genetic Center, Greenville Office, 14 Edgewood Drive, Greenville, SC 29605, USA
Correspondence should be addressed to R. Curtis Rogers, crogers@ggc.org
Received 11 April 2011; Accepted 25 April 2011
Academic Editors: A. Baumer, D. J. Bunyan, B. Mittal, and A. Sazci
Copyright © 2011 R. Curtis Rogers et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Purpose. The objective of this study was to present and describe two additional patients diagnosed with Vici syndrome. Methods.
Clinical, laboratory, and imaging findings of the two siblings are discussed in detail. The two patients’ descriptions are compared
with the other eleven patients reported in the literature. We also presented detailed autopsy results on the male sibling, which
demonstrated cytoplasmic vacuoles of the cardiomyocytes and confirmed the clinical findings. Results. The patients reported here
include the 13th and 14th patients reported with Vici syndrome. The summary of findings present in these patients includes
postnatal growth retardation, developmental delay, bilateral cataracts, agenesis of the corpus callosum, cerebellar anomalies,
gyral abnormalities, seizures, hypotonia, and cardiomyopathy. Conclusion. Vici syndrome should be suspected in any child with
agenesis of the corpus callosum and one of the following findings: cardiomyopathy, cataracts, immune deficiency, or cutaneous
hypopigmentation.
1. Introduction
Vici syndrome was first described in 1988, in two brothers
with agenesis of the corpus callosum (ACC), bilateral
cataracts, cleft lip and palate, hypopigmentation of the
skin and hair, combined immunodeficiency, and severe
psychomotor retardation [1]. The patients died at ages 2 and
3 years from bronchopneumonia. Two other siblings and
two additional patients were described by del Campo et al.
[2]. The major clinical features shared by all patients were
ACC, recurrent infections, hypopigmentation of the skin and
hair, hypotonia, poor postnatal growth, and developmental
delay. The two siblings, a brother and a sister, died at age
2 years and age 11 months due to myocardial failure and
apnea, respectively. One male patient died at age 16 months
following progressive deterioration of cardiac function, and
the final patient, a female, was still living at age 3.5 years.
Based on the presence of the clinical features in two siblings
in two separate families, the pattern of autosomal recessive
inheritance was established.
A third report in the literature by Chiyonobu et al. [3]
presented two additional siblings, a brother and a sister,
with Vici syndrome. The sister died at age 19 months,
possibly due to progressive myocardial failure, while the
brother was still living at age 6 months. Miyata et al. [4]
reported sibling cases of Vici syndrome with complications
of renal tubular acidosis. The sister died at 12 months due
to heart failure, and the brother was still alive at 13 months.
Another report of a patient with Vici syndrome was given by
McClelland et al. [5]. This patient presented with hypotonia,
feeding difficulties, hypertrophic cardiomyopathy, atypical
facies, bilateral cataracts, recurrent infections, and profound
bilateral sensorineural hearing loss. The patient died at 3
months due to deterioration of cardiac function.
An additional report of Vici syndrome was recently
published by Al-Owain et al. [6].Themalehadthree
deceased siblings (2 boys, 1 girl), all with clinical findings
reminiscent of Vici syndrome. The patient died at 9 months
as a result of sepsis, and an autopsy was not performed.
He was the longest living of his affected siblings. Elec-
tromyography (EMG) revealed a myopathic pattern and
pseudomyotonic discharges, and a muscle biopsy showed
marked variation in myofiber size, scattered atrophic fibers,
and rare degenerative and regenerative fibers. The Gomori

2Case Reports in Genetics
trichrome stain revealed a subsarcolemmal vacuolar change
and a focal mild increase in endomysial connective tissue.
The Periodic Acid-Schiff(PAS) stain indicated a buildup
of glycogen in many vacuoles. Nonspecific muscle biopsy
findings were also reported in the patients of del Campo et
al. [2] and McClelland et al. [5].
In this paper we introduce two new patients diagnosed
with Vici syndrome, a brother and a sister who both died
at age 8 years. The autopsy findings of the male sibling
are reviewed, and the neurological findings in the reported
patients are summarized.
2. Materials and Methods
2.1. Patients
2.1.1. Patient 1. Patient 1 was the first pregnancy for his
parents, a nonconsanguineous couple. He was born at
38 weeks gestation after an uncomplicated pregnancy. His
birth weight was 2.46 kg, length was 48.3 cm, and head
circumference was 32.5 cm. At age 11 days, he experienced
an episode of respiratory failure and cardiac arrest. Imaging
studies revealed ACC, enlarged ventricles, hypoplasia of the
cerebellar vermis and brain stem, and cardiomyopathy with
biventricular hypertrophy. Physical examination revealed
mild nystagmus, a high arched palate, fair complexion,
overlapping toes, and hypotonia (Figure 1(a)). Plasma amino
acids, urine amino acids, urine organic acids, serum trans-
ferrin isoelectric focusing, and urine metabolic screen were
normal. Chromosome studies revealed a 46XY karyotype.
Immunological studies showed decreased absolute T cells,
T helpers, and T suppressors, indicating T-cell-mediated
immunodeficiency. Bilateral cataracts were identified at age 4
months. The patient also developed hypothyroidism and had
a history of both seizures and recurrent infections, including
pneumonia and urinary tract infections.
The patient was lost to follow up until his sister was
diagnosed prenatally with ACC during a fetal ultrasound. At
age 6 years, the patient was reported by his parents to have
improvements in seizure frequency and less severe infections
but had significant developmental delay. No significant copy
number variants were noted using the Affymetrix Genome-
Wide SNP 6.0 Microarray system. Several small blocks of
homozygosity (LCSH)/loss of heterozygosity (LOH) regions
were observed (>86 Mb), encompassing greater than 3.01%
of the individual’s genome. The largest block for this patient
was on Chr3: 95741944-98847764 (3.1 Mb) which is below
the threshold of clinical significance.
Patient 1 died at age 8 years due to progressively de-
creasing cardiac function. The autopsy findings included
agenesis of the corpus callosum and cerebellar vermis, absent
thyroid and hypoplastic appearing thymus, and a profoundly
enlarged heart with biventricular dilation. Hypopigmenta-
tion of the retina and fovea was also present. Left ventricular
sections depicted regions of hypertrophied and vacuolated
cardiomyocytes, as well as interstitial and replacement fibro-
sis. Similarly, right ventricular sections demonstrated hyper-
trophied and vacuolated cardiomyocytes, but to a much
lesser extent, and did not contain interstitial or replace-
ment fibrosis. The enlarged and vacuolated cardiomyocytes
contained large, irregular nuclei and membrane-bound
cytoplasmic inclusions within the cardiomyocytes containing
granular material with a “ribbon-like” appearance. The
intracellular inclusions stained positively with Periodic Acid-
Schiff(PAS), and staining was resistant to diastase digestion.
Focal areas of scarring due to ischemic necrosis were seen in
both kidneys. Lung tissue sections were consistent with an
organizing pneumonia, and multifocal areas demonstrated
chronic inflammation with fibrosis and multinucleated giant
cells. Some sections of the cerebellum showed a mild increase
in foveal space with appropriate granular layer and minimal
Purkinje cell loss, while others showed a high increase
in intrafoveal space with degeneration or loss of granular
cell layer and significant Purkinje cell agenesis. The lep-
tomeninges were thin and delicate. Mild polymicrogyria was
present in the occipital regions of the cerebral hemispheres.
Within the deep tissue structures of the brain, specifically the
basal ganglia, there was poor gray/white matter demarcation.
Other brain abnormalities included moderate dilation of
the third ventricle (1 cm) and duplication of the septum
pellucidum. No significant histopathological abnormalities
were seen in the skeletal muscle, lymph nodes, skin, or
adrenal glands.
2.1.2. Patient 2. Patient 2, the sister of Patient 1, was
the third pregnancy for her parents. Prenatal ultrasound
showed intrauterine growth retardation, oligohydramnios,
and agenesis or hypoplasia of the corpus callosum. The
child was delivered by c-section at 33 weeks gestation for
late decelerations and oligohydramnios. The patient was
premature and remained in the NICU for the first six
weeks of life. Her birth weight was 1.225 kg, length 40cm,
and head circumference 26.5 cm. Initial evaluation revealed
hypotonia, ACC, cardiomyopathy, mild micrognathia, and
cutaneous syndactyly of toes 2 and 3 (bilaterally). By age
2 months, she had developed bilateral cataracts, and her
height, weight, and head circumference were less than the
5th percentile. She had also developed a seizure disorder and
mild cardiomegaly. She and her father have a paracentric
inversion of chromosome 2 [46,XX,inv(2)(q21.1q23)], not
related to the disorder. Immunological studies showed
normal absolute lymphocytes, absolute T cells, T helpers,
and CD+3 absolute counts, and elevated CD+4 absolute
counts. In addition to ACC, an MRI at age 2 years revealed
prominent lateral ventricles, dysplasia of the cingulate gyrus,
diffuse white matter atrophy, and atrophy of the brain stem
and the proximal cervical cord.
She was seen again at age 8 years and was undergrown
with a weight of 20 kg, height of 117 cm, and a head
circumference of 42.5cm (5th–10th centile, 5th centile, and
significantly less than the 5th centile, resp.). She displayed
severe developmental delay. She also had spastic quadriplegia
and severe scoliosis. Her hair, irides, and skin were pale.
She had a narrow face with sharp features, a narrow,
high palate with dental crowding, and an asymmetric chest
wall (Figure 1(b)). Her pupils were unreactive to light, and
the optic nerves were atrophic. She had extremely limited

Case Reports in Genetics 3
Tab le 1: Summary of clinical and imaging findings in patients with Vici syndrome.
Previous reports Patient 1 Patient 2 Total
Sex 8 males, 4 females Male Female 9 males, 5 females
Poor growth 12/12 + + 14/14
Developmental delay 12/12 + + 14/14
Atypical facies 12/12 — + 13/14
Cataracts 9/12 + + 11/14
Palatal abnormalities 8/12 + + 10/14
Hypopigmentation 12/12 + + 14/14
ACC 12/12 + + 14/14
Seizures 7/12 + + 9/14
Hypotonia 12/12 + + 14/14
Cardiomyopathy 11/12 + + 13/14
Recurrent infections/immune deficiency 11/12 + + 13/14
+ Indicates presence of symptom.
— Indicates absence of symptom.
Tab le 2: MRI findings in patients with Vici syndrome.
ACC
Hypoplasia
of cerebellar
vermis/hemispheres
Hypoplasia
of pons
Cerebral
atrophy/
hypoplasia
Absent
septum
pellucidum
Dilated
ventricles Heterotopia
Poly microgyria/
abnormal
gyration
Past
cases
(1) + (?)
(2) + + + — —
(3) + + + +
(4) + + +
(5) + +
(6) + +
(7) + +
(8) +
(9) + +
(10) + +
(11) + + + +
(12) + + + + +
Present
cases
(13) + + — — — + — +
(14)+ — ————— +
+ Positive finding.
— Negative finding was specifically indicated in the literature.
(?) Patient 1 was assumed to have ACC due to positive ACC findings in sibling and clinical evaluation.
Blank space indicates that nothing was mentioned about that particular area in the literature.
movement of her legs with contractures of her knees and
ankles and milder contractures of the elbows. She had
idiopathic dilated cardiomyopathy and a left ventricular
shortening fraction of 34%. She has roughly 20 infantile
spasms daily. Follow-up cardiac evaluations have demon-
strated persistently borderline left ventricular function. The
patient’s respiratory status progressively worsened, and she
died at age 8 years. An autopsy was not performed.
3. Results and Discussion
The siblings reported here represent the 13th and 14th
patients clinically diagnosed with Vici syndrome. Both have
postnatal growth retardation, developmental delay, bilat-
eral cataracts, agenesis of the corpus callosum, cerebellar
anomalies, gyral abnormalities, cardiomyopathy, seizures,
and hypotonia. Tabl e 1 provides a summary of the clinical
and imaging findings of the siblings that we describe and the
other patients who have been reported in the literature.
Of the fourteen patients presented, nine are male and
five are female. All reported patients (14/14) have agene-
sis of the corpus callosum, postnatal growth retardation,
developmental delay, hypopigmentation of the hair and/or
skin and/or retina, and hypotonia. Approximately 93%
(13/14) of patients have atypical facies, cardiomyopathy, and
recurrent infections/immune deficiency. Over half of the
patients have cataracts (11/14), abnormalities of the palate
(10/14), cerebellar abnormalities (9/13), seizures (9/14), and

4Case Reports in Genetics
(a) (b)
Figure 1: (a) Patient 1 and his sibling, (b) Patient 2, at 2 weeks and 6 years, respectively. Both patients have hypopigmentation and profound
intellectual disability.
gyral abnormalities (8/13). Additionally, in the first patients
reported by Vici et al. [1], one male was affected with
hypospadias.
Tab l e 2 shows a more comprehensive summary of the
neurological abnormalities described in patients diagnosed
with Vici syndrome. In addition to ACC, 6 patients report-
edly had hypoplasia of the cerebellar vermis or cerebellar
hemispheres, 5 patients had dilated ventricles, 4 patients
had polymicrogyria/abnormal gyration, 3 patients had cere-
bral atrophy/hypoplasia, 2 patients had an absent septum
pellucidum, and 2 patients had hypoplasia of the pons. In
addition, there were single case reports of heterotopia and
lung hypoplasia. Interestingly, the autopsy report of Patient 1
revealed a duplication of the septum pellucidum, a very rare
finding (especially in conjunction with ACC).
While Vici syndrome is associated with many different
congenital malformations, we suggest that this disorder
should be suspected in any child with agenesis of the corpus
callosum and one of the following findings: cardiomyopathy,
cataracts, recurrent infections/immune deficiency, or cuta-
neous hypopigmentation. All the patients have severe devel-
opmental delay, and most have died within the first three
years of life secondary to cardiomyopathy or pneumonia.
Although our male patient did not show skeletal muscle
abnormalities, the muscle biopsy findings in the patients of
del Campo et al. [2], McClelland et al. [5], and Al-Owain et
al. [6] indicate that Vici syndrome may be a glycogen storage
disorder. Further investigation is warranted to determine
whether glycogen accumulation is a primary or secondary
sign of Vici syndrome.
Conflict of Interests
The authors have no financial, academic, or personal conflict
of interests.
References
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the corpus callosum, combined immunodeficiency, bilateral
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[2] M. del Campo, B. D. Hall, A. Aeby et al., “Albinism and agenesis
of the corpus callosum with profound developmental delay:
Vici syndrome, evidence for autosomal recessive inheritance,”
American Journal of Medical Genetics, vol. 85, no. 5, pp. 479–
485, 1999.
[3] T. Chiyonobu, T. Yoshihara, Y. Fukushima et al., “Sister and
brother with Vici syndrome: agenesis of the corpus callosum,
albinism, and recurrent infections,” American Journal of Medical
Genetics, vol. 109, no. 1, pp. 61–66, 2002.
[4] R. Miyata, M. Hayashi, H. Sato et al., “Sibling cases of Vici
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[6] M. Al-Owain, A. Al-Hashem, M. Al-Muhaizea et al., “Vici
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