Pallister-Killian Syndrome: Report of One Case
HUI-CHUNG WU1, LUNG-HUANG LIN1 2, LI-PING TSAI3, CHENG-HUNG HUANG4,
KUN-LONG HUNG4, HUNG-TSAI LIAO5
Pallister-Killian Syndrome (PKS) is a rare sporadic congenital anomaly disorder, characterized
by multiple congenital anomalies, especially craniofacial dysmorphism. It is also associated with
mental retardation, seizure, skin pigmentation, and visceral malformations such as congenital
diaphragmatic hernia, congenital heart defect, anorectal anomalies, and genital malformation.
This syndrome usually presents with tissue-limited mosaicism of supernumerary 12p isochromosome i
(12p). Moreover, diagnosis of Pallister-Killian Syndrome (PKS) is difficult because the ratio of
abnormal to normal karyotyping is much lower in peripheral lymphocytes than in skin fibroblasts.
We report the first case in Taiwan, who has tetrasomy 12p mosaic in peripheral lymphocytes. (Acta
Paediatr Tw 2006; 47:139-41)
Key words: tetrasomy 12p, Pallister-Killian syndrome, congenital anomalies
Pallister Killian syndrome (PKS) is a rare sporadic
congenital anomaly, first described by Pallister et al in
1977 and later by Killian and Teschler-Nicola in 1981. It
had been called Pallister mosaic syndrome, Killian/
Teschler-Nicola syndrome, tetrasomy 12p, isochromosome
12p mosaic. This syndrome is characterized by craniofacial
abnormalities including sparse anterior scalp hair,
particularly in temporal areas during infancy, sparse
eyebrows and eyelashes, prominent forehead, up-
slanting palpebral fissures, ocular hypertelorism, ptosis,
strabismus, flat broad nasal root with anteverted nostrils,
long philtrum with thin upper lip, protruding lower lip,
large ears with thick protruding lobules, posteriorly
rotated ears, and short neck. Patients with this syndrome
usually present profound mental deficiency with only
minimal speech development, seizures, contractures
developing with advancing age, muscular hypotonia,
deafness, streaks of hyper- or hypo- pigmentation, poor
pigmentation of retina, broad hands with short digits,
accessory nipples, and disproportionate shortening of
arms and legs.1,2 Variable visceral malformations including
diaphragmatic hernia, congenital heart defect, anorectal
Department of Pediatrics, Cathay General Hospital1, Taipei; College of Medicine, Fu-Jen Catholic University,
Hsinchuang2, Taipei; Department of Pediatrics, Buddhist Tzu Chi General Hospital Taipei Branch3, Taipei, and Cathay
General Hospital- Sijhih4, Taipei, and Cathay General Hospital- Hsinchu5, Hsinchu , Taiwan.
Received: March 13, 2006. Revised: June 19, 2006. Accepted: July 10, 2006.
Address reprint requests to: Dr. Cheng-Hung HUANG, Department of Pediatrics, Cathay General Hospital- Sijhih,
No. 2, Lane 59, Jiancheng Rd. , Sijhih City, Taipei, 221, Taiwan.
anomalies, and genital malformation were also reported.3
There was a 1-day-old female newborn, who was born
to a 28-year-old gravida 2, para 2 healthy mother and
a 31-year-old father at 39 weeks gestation via C/S due
to fetal distress. Her birth weight was 3095 gm (25-50th
percentile), body length was 48 cm (25-50th percentile),
and head circumference was 34 cm (50-75th percentile).
The Apgar score revealed 5 at 1st minute, 6 at 5th minute,
and 8 at 10th minute. There was no premature rupture
of membrane, no meconium stain in amniotic fluid, and
no maternal fever. After delivery, generalized skin
cyanosis, decreased muscle tone, poor respiratory trigger
but heart rate more than 100/min were noted. Oxygen
with positive pressure was given immediately, then the
skin color turned to pink gradually. Under the impression
of respiratory distress, the patient was transferred to
the NICU. Her parents were healthy and already had a
healthy child. At NICU, in addition to dusky skin color,
weak crying, and hypotonia, we also found multiple
minor dysmorphism including prominent forehead with
frontal bossing, sparse scalp hair with bitemporal alopecia,
Acta Paediatr Tw
Pallister-killian syndromeVol. 47, No. 3, 2006140
sparse eyebrows, mild hypertelorism, depressed nose
bridge, anteverted nostrils, thin upper lip, thick lower
lip (Fig. 1), high arch palate, lower set ears, posteriorly
rotated ears, large fontanelle (4.5 cm× 4 cm), short neck,
accessory nipples, clenched hands with simian crease,
anterior displaced anus (Fig. 2), mildly rocket-bottom
feet, hypotonia, and deep tendon reflex (+/-).
Echocardiography showed mitral regurgitation, and
patent foreman ovale. Brain sonogram revealed
dysgenesis of the corpus callosum, and bilateral
colpocephaly. There was no hydronephrosis by renal
sonogram. Neither vertebrae anomaly nor other bone
deformity was noted by whole-body X-ray. The
chromosome study of peripheral lymphocytes revealed
47, XX, +i (12) (p10) /46, XX  (Fig. 3), which
was compatible with the result of CGH (Comparative
Genomic Hybridization) (Fig. 4). Moreover, poor feeding
due to weak sucking power was noted during admission.
Under the impression of Pallister-Killian syndrome (PKS),
Fig. 1. Sparse scalp hair with bitemporal alopecia,
sparse eyebrows, mild hypertelorism,
depressed nasal bridge, anteverted nostrils,
thin upper lip, thick lower lip.
Fig. 3. Chromosome analysis: the karyotype: 47,
Fig. 4. CGH (Comparative Genomic Hybridization)
reveals expansion of chromosome 12p.
we performed skin fibroblast karyotyping which also
revealed 47, XX, +i(12)(p10) /46, XX.
Chromosome studies of her parents were both normal.
Now, the patient has severe psychomotor retardation
and receives regular physical rehabitation. Failure to
thrive has also been noted (body length: 70 cm, body
weight 9 kg at 2.5years old, both below 3rd percentile)
The etiology of PKS is mosaic tetrasomy of the short
arm of chromosome 12.4 The diagnosis is according to
chromosome analysis; however, the i(12p) is usually
present in fibroblasts but rarely in peripheral blood
lymphocytes. Frequency of mosaics decreases both in
vivo with older age of probands and in vitro with later
passage of cell cultures.1,2 Mechanism of formation and
parental origin of the isochromosome are not well
H.C. WU, L.H. LIN, L.P. TSAI, et al. Download full-text
Acta Paediatr Tw
understood. A meiotic II nondisjunction, followed by
a centromeric misdivision, may be the most likely
mechanism for i(12p) formation in this syndrome.5 Older
maternal age was found to be a significant risk factor for
chromosomal nondisjunction. In most analyzed cases,
the i(12p) chromosome was shown to be of maternal
origin, but at least one case with paternal origin was
reported.2 Cells containing the i(12p) will subsequently
be lost because of the incompatibility of this genotype
with survival.5 Besides, a correlation between the
percentage of i(12p) cells in skin fibroblasts and the
phenotypic severity is not striking.
Tissue-specific mosaic distribution of an additional
isochromosome 12p is the characteristic chromosomal
aberration in PKS. A case diagnosed prenatally by 4
different tissues was analyzed. From direct preparation
of chorionic villi at 21 gestational weeks showed an extra
marker chromosome in 19% but two additional copies
in 3%. From amniocytes at 17 and 21 gestation weeks,
the i(12p) was observed in 23% and 12%, respectively.
The long term culture of fibroblasts from umbilical cord
showed the i(12p) in 100% of metaphase but absent in
cultured lymphocytes from fetal blood at 21 gestational
weeks.6 Because of the tissue-specific distribution,
prenatal diagnosis of PKS is often difficult, and the
frequency is probably underestimated. Gilgenkrantz et
al. reported the first prenatal diagnosis of PKS in 1985.
Since then, among the 63 reported fetuses, 59 fetuses
had prenatal diagnosis. The three most frequent
ultrasound indicators were hydramnios (84%), congenital
diaphragmatic hernia (16%), and micromelia of
predominantly rhizomelic type (10%). Fetuses with the
above findings are highly suggestive of tetrasomy 12p;
however, cases without ultrasound anomalies but
presenting with non-specific minor anomalies should have
the fetal face examined carefully, which might contribute
to directing the diagnosis towards PKS. Tetrasomy 12p
may be diagnosed from the end of the first trimester of
pregnancy by chorionic villus cytogenetic analysis. It
is necessary to perform both direct and culture analyses
because of a progressive decrease of the isochromosome
with culture aging.7
In 2003, there was an unusual case of i(12p) in a 15-
year-old boy presenting with mild mental retardation,
minor facial features (long face, prognathism, short
neck), hyperpigmented streaks, normal weight, length,
and occipitofrontal circumference parameters. The boy
attended normal school until the age of 14 years.
Because of hyperpigmented stripes, he received
chromosome analysis of skin fibroblasts. This study
showed that 37% of the cells had an additional
isochromosome for the short arm of chromosome 12.
This observation illustrates the phenotypic variability
of i(12p) and emphasizes the importance of skin fibroblast
chromosome analysis in patients presenting with
pigmentary skin changes. In review of 51 published
postnatal cases with PKS, the classical features were
severe mental retardation, seizure, hypotonia, a “coarse”
facial appearance, a broad forehead, bilateral
temporofrontal alopecia, flat nasal bridge, hypertelorism
and variable visceral malformation. Interestingly, facial
features may change with age, such as bitemporal
alopecia seems to disappear but prognathism, and
macrostomia may develope with age; however, coarse
face with prominent upper lip still persisted. Therefore,
skin biopsy for chromosome analysis may be considered
in adults presenting with mental retardation, coarse face,
and prognathism even in the absence of skin pigmentary
The main differential diagnosis is the recessive
autosomal-inherited Fryns syndrome, which is also
associated with congenital diaphragmatic hernia. Fetal
growth evaluation such as fetal hypotrophy and
microcephaly are more frequently presented in Fryns
syndrome than in PKS.7
In conclusion, we have found 47, XX, +i(12) (p10)
/46, XX  from peripheral lymphocyte, which was
reported worldwide in a small number of cases, but not
previously in Taiwan. Therefore, when there is a
craniofacial dimorphism suspected tetrasomy 12p mosaic,
skin fibroblast karyotyping should be considered even
in the absence of the peripheral lymphocyte karyotype.
1. Jones KL. Smith’ s recognizable patterns of human
malformation, 5th ed. Philadelphia: WB. Saunders
Company, 1997; 208-9.
2. Leube B, Majewski F, Gebauer J, et al. Clinical,
cytogenetic, and molecular observations in a patient with
Pallister-Killian –syndrome with an unusual karyotype. Am
J Med Gen 2003; 123:296-300.
3. Schinzel A. Tetrasomy 12p(Pallister-Killian syndrome). J
Med Gen 1991; 28:122-5.
4. Edward Gruson et al. NORD guide to rare disorders.
Baltimore: Williams & Wilkins, 2004; 231.
5. Struthers JL, Cuthbert CD, Khalifa MM. Parental origin of
the isochromosome 12p in Pallister-Killian syndrome:
Molecular analysis of one patient and review of the re-
ported cases. Am J Med Gen 1999; 84:111-5.
6. Schubert R, Viersbach R, Eggermann T, Hansmann M,
Schwanitz G. Report of two new cases of Pallister-Killian
syndrome confirmed by FISH: tissue-specific mosaicism
and loss of i(12p) by in vitro selection. Am J Med Gen
7. Doray B, Girard-Lemaire F, Gasser B, Baldauf JJ,
Geeter B, Spizzo M, et al. Pallister-Killian syndrome: dif-
ficulties of prenatal diagnosis. Prenatal diagnosis 2002;
8. Genevieve D, Cormier-Daire V, Faivre L, et al. Mild phe-
notype in a 15-year-old boy with Pallister-Killian syndrome.
Am J Med Gen 2003; 116:90-3.