American Journal of Medical Genetics (Neuropsychiatric Genetics) 81:269–270 (1998)

Letter to the Editor

On Cognitive Variability in Velocardiofacial
Syndrome: Profound Mental Retardation and Autism

To the Editor: cleft palate, missing central incisors, and multiple den-
tal caries (Fig. 1). She had no murmurs. Examination
In this report I describe a young woman with velo- of the spine and extremities revealed kyphoscoliosis,
cardiofacial syndrome and 22q11 microdeletion. The clinodactyly of the fifth fingers, highly inserted
proposita has profound mental retardation and autism, thumbs, poorly defined palmar creases, high-arched
features which have not been reported previously in feet, and a wide distance between the first and second
the literature. toes. She had normal secondary sexual characteristics.
The proposita was born following a pregnancy com- The neurological examination revealed tightness in the
plicated by monthly bleeding, resembling menstrual Achilles tendons and exaggerated deep tendon reflexes.
bleeding, during the first 4 months. The gestation was High-resolution chromosome analysis revealed nor-
otherwise normal. The mother was 37 years old at the mal findings. Dosage analysis was performed utilizing
time of conception and it was her only pregnancy. The
proposita was born prematurely with a birth weight of
2,270 g and a length of 42.5 cm. She had a unilateral
cleft lip and palate which was repaired early in life. At
age 3 years she was given the diagnosis of autism due
to severe developmental deficits, poor social interac-
tion, and disturbances in cognition and interpersonal
communication. She was enrolled in special education
services. At age 15 years, due to severe behavioral
problems, she was prescribed neuroleptics, which re-
sulted in tardive dyskinesia. Cat scan of the head and
abdominal imaging revealed normal findings. The fam-
ily history was significant for alcoholism and depres-
sion on the maternal side.
When evaluated at age 22 years, she had an IQ of 13
on the Slosson Intelligence Test and the Vineland
Adaptive Behavior Scale. Her language findings scat-
tered between 1–8 months of developmental level. She
was incontinent. On physical examination, she had sig-
nificant growth retardation. All of her growth param-
eters were far below the 2nd centile. Her height was
140 cm, weight 38 kg, and OFC 52 cm. She did not
make eye contact, had a very short attention span, and
engaged in head-banging behavior. She had fine ath-
etoid movements of the lips, tongue, and fingers. She
had multiple scars secondary to self-injurious behav-
iors. She had facial asymmetry, flat face, square nasal
root, asymmetry of the nares with deviation of the na-
sal septum to the right, ptosis of the right eyelid, and
borderline low-set ears. Each ear measured 6 cm (50th
centile). She had a right cleft lip with a corresponding

*Correspondence to: Chahira Kozma, M.D., Child Development

Center, Georgetown University Medical Center, 3307 M Street
Fig. 1. Proposita at age 13 years. Note squared nasal root, collapsed
N.W., Suite 401, Washington, DC 20007-3935. right nostril due to unilateral cleft lip, dimple on the chin, and facial asym-
Received 29 October 1997; Revised 13 January 1998 metry.

© 1998 Wiley-Liss, Inc.

270 Kozma
two markers, N2S and N4L, within the DiGeorge criti-
cal region. A deletion of both markers was detected.
The mother had normal molecular cytogenetic testing.
The father was not available for testing.
Velocardiofacial syndrome is a major malformation
syndrome characterized by typical facies, cardiac de-
fects, palatal abnormalities, and learning disabilities.
In the majority of cases it is associated with 22q11
microdeletion. Neurobehavioral involvement is a major
feature of the syndrome and has been estimated to oc-
cur in between 82–99% of affected individuals. In the
majority of cases, the cognitive impairment involves
learning disabilities or mild mental retardation, and
psychiatric problems have been reported in a large
number of affected individuals [Golding-Kushner,
1985; Goldberg et al., 1993]. Severe mental retardation
was reported in a very few instances [Lipson et al.,
1991].
This case describes a woman with velocardiofacial
syndrome and 22q11 deletion, associated with pro-
found mental retardation and autism. Autism is a de-
velopmental disorder characterized by serious impair-
ment in the development of social skills, delayed lan-
guage development, ritualistic and compulsive
behavior, and onset before age 30 months. In addition,
the proposita suffered from tardive dyskinesia, a con-
dition of involuntary repetitive movements of the face,
extremities, and trunk, secondary to the use of psycho-
tropic medications. This is an important complication
for clinicians to be aware of, since a large number of
affected individuals may require the intake of psycho-
tropic medications for their psychiatric problems.
The proposita had a cleft lip, a physical finding which
has been reported in about 5% of those affected with
velocardiofacial syndrome [Lipson et al., 1991]. The
presence of cleft lip in this case contributed to the pres-
ence of secondary facial abnormalities such as nasal
asymmetry, septal deviation, and incomplete tooth de-
velopment on the side of the cleft. In addition to cleft
lip, the proposita had profound mental retardation,
which is also seen infrequently in velocardiofacial syn-
drome, raising the question of whether these two char-
acteristics are associated.
This case represents a further expansion on the cog-
nitive impairment, physical characteristics, and neuro-
behavioral spectrum of velocardiofacial syndrome.
REFERENCES
Goldberg R, Motzkin B, Marion R, Scambler P, Shprintzen RJ (1993): Velo-
cardio-facial syndrome: A review of 120 patients. Am J Med Genet
45:313–319.
Golding-Kushner KJ, Weller G, Shprintzen RJ (1985): Velo-cardio-facial
syndrome: Language and psychological profiles. J Craniofac Genet 5:
259–266.
Lipson AH, Yuille D, Angel M, Thompson PG, Vandervoord JG, Beckena-
ham EJ (1991): Velo cardio facial (Shprintzen) syndrome: An important
syndrome for the dysmorphologist to recognize. J Med Genet 28:596–
604.
Chahira Kozma*
Child Development Center/
Department of Pediatrics
Georgetown University Medical Center
Washington, DC