Over 30 cases of del(9p) have been reviewed recently, the majority being
de novo. We report 11 new cases of which seven have del(9p) as the sole anomaly
and four have del(9p) with another unbalanced chromosome segment. In each of
these two groups of patients, the order in which our cases are presented is a
function of the length of the deleted segment, starting with the longest. It
appears that dysmorphic features do not differ according to the length of the
deletion. We summarize the features from 80 cases (table).
Patients and methods
In the following descriptions, only features which are not included in
the appendix will be described. A diagram showing the breakpoints on chromosome
9 is shown in fig 1. Each karyotype was performed with RHG banding except in
case 2 where GTG banding was used.
Fig 1. - Breakpoints on
chromosome 9p in present cases (left, cases 1 to 7: del (9p) as the sole
anomaly; right, cases 8 to 11: del (9p) with another unbalanced segment).
CASE 1*: 46,XX,del(9)(p21)
The proband (fig 2A) was the first child of healthy parents.
Delivery was induced at 43 weeks' gestation.
* Cases cited in reference 56.
CASE 2: 46,XY,del(9)(p22)
The parents of the proband had previously had 11 children, three of
whom died in early infancy with-out any detectable malformation. There was
apparent hypertelorism but a decreased interorbital distance was ascertained by
radiography, small alae nasi, truncal hypotonia, and hypertonia of the
extremities. Numerous seizures occurred but repeated electroencephalography did
not show any anomaly. Surgery for craniostenosis was performed at the age of
nine months. At the age of two years three months, dysmorphic features were
unchanged (fig 2B). The patient understood simple requests but did not
CASE 3: 46,XX,del(9)(p22)
The proband (fig 2C) was the first child of healthy parents.
CASE 4*: 46,XX,del(9)(p22)
A girl with seven healthy sibs was referred to us at the age of one
year four months (fig 2D). She pre-sented with microcephaly, turricephaly, and
tri-angular shaped auditory canals. Her bone age was advanced (two years at one
year four months).
CASE 5: 46,XX,del(9)(p23)
A girl with four healthy older sibs was referred to us when she was
four years old. There were absent lacrimal ducts, deafness, kyphoscoliosis, and
hypoplasia of the labia majora (fig 2E).
CASE 6: 46,XX,del(9)(p23)
A girl (fig 2F) with one healthy sib was born after a pregnancy
complicated by hydramnios. A cardiac murmur was present but no anomalies were
de-tected with ultrasound. She rapidly developed res-piratory distress and was
transferred to the intensive care unit. Radiography ascertained choanal
atresia. Surgery was performed but the patient died at the age of two months
from respiratory failure.
CASE 7: 46,XX,del(9)(p23)
A four year old girl with two normal sibs was refer-red to us to
confirm a probable trisomy 21. Clinical examination showed a moon shaped face,
flat occi-put, epicanthus, low nasal bridge, but also trigonocephaly, long
philtrum, widely spaced nipples, dolichomesophalangy, proximally placed thumbs,
and five whorls (fig 2G).
CASE 8*: 46,XY,-9,+der(9),t(9;12)
The proband was born after an uneventful preg-nancy. There had been
a previous miscarriage. At delivery, an infarction of the placenta was noted.
The proband presented with trigonocephaly and tur-ricephaly, hypoplastic alae
nasi, narrow ear canals, bilateral hexadactyly, hypospadias, and deafness (fig
2H). Numerous episodes of pneumonia occur-red. At the age of two months an
advanced bone age was noted. He died from pneumonia at seven months. Necropsy
showed a coarctation of the aorta. The karyotype showed monosomy 9p21?pter
and trisomy 12q24?qter.
CASE 9**: 45,XX,-9,-21,+der(9),t(9;21) (p21 or 22;q11 or
The proband was the first child of healthy parents. Her Apgar scores
were 8 at one minute and 4 at five minutes. Clinical examination (fig 21)
showed a high, flat forehead, scaphocephaly, microphthalmos, very marked
nasolabial furrow, slight prognathism of the upper maxillary bone, vermilion
border of the upper lip visible only at the level of the cupid's bow, normal
philtrum, crux cimbae and adherent lobuli, narrow auditory canals, small nails,
lack of flexion crease on the third and fourth ringers, camptodactyly of the
fifth finger, bilateral talipes valgus, no whorls, seven archs, umbilical and
inguinal herniae, and a cardiac murmur. She died at the age of two years.
Necropsy showed a ventricular septal defect and malformed kidneys. The
karyotype showed monosomy 9p21 or 22?pter and monosomy 21pter?q11 or
** Case partially reported in reference 55.
The proband (fig 2J) was born at 32 weeks of pregnancy. Her parents
had previously had five miscarriages. Growth retardation was noted one week
before birth. There was a severe cardiac anomaly. The anus was anteriorly
placed with a cleft towards the vagina. She died suddenly at the age of three
months. Necropsy showed hypertrophy of the right ventricle, hypoplastic
pulmonary arteries, a philtrum, nose with stunted tip, short, broad, and webbed
neck with low hair line, excess of whorls on the fingers, dolichomesophalangy
with extra finger flexion creases (countertype of trisomy 9p syn-drome), and
the diagnosis should be suspected at birth. Other signs, although often
present, are not specific for this condition (epicanthus, hypertelorism,
microretrognathia, low set ears, abnormal tone, etc). A cardiac murmur is often
present but cardiac surgery is rarely necessary. Herniae and minor
abnormalities of the external genitalia and scoliosis or kyphosis are often
encountered. After infancy, pyramidal tract signs, epilepsy, strabismus,
nystagmus, and dental anomalies can occur (reported in three or four cases
each). Mean IQ is 49 (SD 13) (range 33 to 73, n=14). Social adaptation is often
good. One case has been diagnosed at the age of 61.
9p deletion with another unbalanced chromosome
The number of del(9p) cases associated with a partial trisomy has
been underestimated in the past since cases are often reported as 'a case of
trisomy . . .'. We reviewed 41 cases of 9p- with an associated unbalanced
chromosome segment, which is approximately half of the total number of cases.
Most of them are inherited from a balanced translocation carrier (mother 25
cases, father 13 cases). The breakpoint can occur at 9p22 (nine out of 38
cases), the most common site in pure 9p-, but occurs mainly at 9p24 (23 out of
38 cases). This breakpoint has not been described in cases where 9p- is the
sole anomaly, which may in part be because of the difficulty of karyotypic
ascertainment of such a terminal deletion when isolated. Sex ratio appears to
be 1.7 females/1 male ( etest, NS)*. Mean parental ages at birth are 25-2 (SD
3.7) (mother) and 27.9 (SD 4.3) (father). A family history of miscarriages or
previous malformed children is present in half of the cases. The pregnancy is
usually uneventful: mean birth weight is 2.9 kg (SD 0-6). Mean IQ is 46 (SD 9)
(range 33 to 57, n=7). The associated unbalanced chromosome segment is variable
(table) but four trisomy 13q, three trisomy 12q, three trisomy 10q, two trisomy
2q, two trisomy 5p, two trisomy 5q, two trisomy 7q, and two trisomy 16q were
found in unrelated patients. Breakpoints on the trisomic segment are variable
apart from 13q21 or 22 (four cases), 10q25 or 26 (three cases), 5q31 or 32, and
12q24 (two cases each). Trigonocephaly, long philtrum, dolichomesophal-angy,
and hernia are often found in cases of del(9p)
* When cases of 9p- as the sole anomaly and cases with another
unbalanced segment are pooled, a significantly unbalanced sex ratio appears.
However, as the chromosomal mechanism is different, it does not seem valid to
pool these two groups of patients. With another unbalanced segment. However,
the phenomenon of epistasis is difficult to ascertain in certain cases since it
cannot be based on objective investigations and measurements. It should be
noted that 16 del(9p) patients with another unbalanced segment and only one
patient with del(9p) as the sole anomaly have been reported to die in
Fig 2. - A, B, C Patients 1 to 3: cases of
del(9p) as the sole anomaly. Arrow: dolichomesophalangy with extra finger
Table - Main features from 80 cases of del (9p)
|As the sole anomaly (39
cases)||With other unbalanced segment (41 coses)
|No of cases or mean value||No of informative
cases||No of cases or mean value||No of informative cases
|Sex ratio||15 M/24 F||n=39||15 M/26
(prominent occiput 4/10)
(large mouth 5/12)
|High arched and/or cleft
|Extra finger flexion
|Increased total ridge
|Early reports (refs 1 to 3) have not been
included in this review since no banding was available, and it cannot be
ascertained if del(9p) was the sole anomaly. Cases of del(9p) as the sole
anomaly were reported in refs 4 to 28 and cases of del(9p) associated with
another unbalanced segment in refs 5 and 29 ta 54. Present cases are included.
*In one case, the deletion was interstitial: del(9)(pl3.3?p23). ? =
increased. ? = decreased. Note: Other unbalanced segments were:
dup(2)(q31?qter); dup(2)(q33?qter); dup(3)(q25?qter); dup(4)(p14?pter);
dup(4)(q23?qter); dup(5)(p13?pter);dup(5)(p?); dup(5)(q31?qter);
dup(5)(q32?qter); dup(6)(p21?pter); dup(7)(q2l?qter); dup(7)(q31?qter);
dup(10)(q25?qtert); dup(10)(qter);dup(12)(p11?pter); dup(12)(q21?qter);
dup(12)(qter); dup(13)(q21?qter); dup(13)(q22?qter); dup(15)(qter);
dup(16)(q13?qter); dup(16)(qter);dup(18)(q12?qter); dup(20)(p?);
del(9)(q00?q21); del(15)(pter?qll); del(21)(qll or 21?qtcr);
t(9;13)(p22;a34) apparently balanced.
1 Condron CJ, Thomas GH. K-deleted group chromosomes. Birth Defects
2 Elliott D, Thomas GH, Condron CJ, Khuri N, Richardson F. C-group
chromosome abnormality (?10p-); occurrence in a child with multiple
malformations. Am J Dis Child 1970;199:72-3.
3 de Grouchy J, Lautman F. Caryotype 46,XX,1q-, 2q-, Dq+, 16q+ chez
une enfant polymalformee. Ann Genet (Paris) 1968;H:129-31
4 Alfi OS, Sanger RG, Sweeny AE, Donnell GN. 46,del(9)(22:). A new
deletion syndrome. Birth Defects 1974; 10:27-34.
5 Alfi OS, Donnell GN, Crandall BF, Derencsenyi A, Menon R. Deletion
of the short arm of chromosome 9 (46,9p-): a new deletion syndrome. Ann Genet
6 Alfi OS, Donnell GN, Allderdice PW. Derencsenyi A. The 9p- syndrome.
Ann Genet (Paris) 1976:19:11-6.
7 Allderdice PW, Heneghan WD, Felismino ET. 9pter?p22 deletion
syndrome: a case report. Birth Defects 1976;12,No 5: 151-5.
8 Breg WR, Aronson MM, Hill R, Grecne AE, Coricll LL. Deletion in the
short arm of chromosome 9 from a subject with congenital cerebral
maldevelopment. Cytogenet Cell Genet 1976;17:296-7.
9 Bricarelli FD. Magnani M, Arslanian A, et al. Expression of GALT in
two unrelated 9p- patients. Evidence for assignment of the GALT locus to the
9p21 band. Hum Genet 1981;59:112-4.
10 Daniel A, Ekblom L, Philips S, Fitzgerald JM, Opitz JM. NOR
activity and centromere suppression related in a de novo fusion
tdic(9;13)(p22;pl3) chromosome in a child with del(9p) syndrome. Am J Med Genet
11 Deroover J, Fryns JP, Parioir C, Haegeman J, Van den Berghe H.
Partial monosomy of the short arm of chromosome 9; a distinct clinical entity.
Hum Genet 1978;44:195-200.
12 Fryns JP, Pedersen JC, Duyck H, Fabry G, Van den Berghe H. Deletion
of the short arm of chromosome 9; a clinically recognisable entity. Eur J
13 Funderburk SJ, Sparkes RS, Klisak I. The 9p- syndrome. J Med Genet
14 Hahn DA. Byrd JR, Ho CK. Birth Defects 1978;14,(6C):414.
15 Hernandez A, Rivera H, Jiménez-Sainz M, Fragoso R, Nazara Z, Cantu
JM. Type and contretype signs in monosomy and trisomy 9p; on a case
46,XY,del(9)(pter?pl2). Ann Genet (Paris) 1979;22:155-7.
16 Kadotani T, Watanabe Y, Kurose Y. A case of partial monosomy for
the short arm of the chromosome No 9. Proc Japan Acad 1984;60:24-7.
17 Kuroki Y, Yokota S, Nakai H, Yamamoto Y, Matsui I. A case of 9p-
syndrome. Hum Genet 1977 ;38:107-11.
18 Lajarrige C, Bouquier JJ, Ronayette D, et al. Monosomie 9p. A
propos d'une nouvelle observation; etude clinique et cytogenetique. Ann Pediatr
19 Monaghan HP, Howard NJ. Short stature and microgenitalia in the 9p-
syndrome. Isr J Med Sci 1981:150:382-4.
20 Mulcahy MT. Another case of 9p- syndrome. Ann Genet (Paris)
21 Nielsen J, Homma A, Christiansen F, Rasmussen K, Saldana-Garcia P.
The deletion 9p syndrome. A 61-year-old man with deletion of short arm 9. Clin
22 Pavone L, Mollica F, Sorge G, et al. Une nouvelle observation de
monosomie partielle 9. Ann Genet (Paris) 1978;21:186-8.
23 Rutten FJ, Hustinx TWJ, Dunk-Tillemans AAW, et al. A case of
partial 9p monosomy with some unusual clinical features. Ann Genet (Paris)
24 Serville F, Allain D, Broustet A, et al. Deletion partielle du bras
court du chromosome 9. Ann Genet (Paris) 1976;19:143-7.
25 Szymanska J, Gutkowska A, Kubalska J, et al. 9p- syndrome: two new
observations. Klin Padiatr 1984;191:121.
26 Wisniewski L, Szymanska J, Niezabitowska A, et al. Two new cases of
9p- syndrome. Klin Padiatr 1980;192:270-4.
27 Young RS, Reed T, Hodes ME, Palmer CG. The dermato-glyphic and
clinical features of the 9p trisomy and partial 9p monosomy syndromes. Hum
28 Young RS, Bader P, Palmer CG, etal. Brief clinical report. Two
children with de novo del(9p). AmJ Med Genet 1983;14:751-7.
29 Bergamo F, Crosato F, Francesconi D, et al. The 9p- deletion
syndrome: a patient with a 45,XX,-9,-15,+t(9/15) constitution due to maternal
3:1 meiotic disjunction. Clin Genet 1977;11:219-23.
30 Berger R, Turc C, Wachter H, Begue G. Partial 7q trisomy. Clin
31 Buckton KE, Barr DGD. Partial trisomy for long arm of chromosome
16. J Med Genet 1981;18:483.
32 Crane J, Sujansky E, Smith A. 4p trisomy syndrome: report of 4
additional cases and segregation analysis of 21 families with different
translocations. Am J Med Genet 1979;4:219-29.
33 Eden MS, Thelin JW, Michalski K, Mitchell JA. Partial trisomy 6p
and partial monosomy 9p from a de novo translocation
46,XY,-9,+der(9)t(6:9)(p211:p24). Clin Genet 1985;28:375-84.
34 Fallström SP, Wahlström J. A pericentric inversion of chromo-some
9 and a rearrangement involving chromosomes 9 and 10, observed in two
generations. Clinical description of chromo-some 9(p12-p21) deletion syndrome.
Clin Genet 1979;15:480-6.
35 Hoo JJ. 12p trisomy: a syndrome? Ann Genet (Paris)
36 Hoo JJ, Parslow MI, Shaw RL, Veale AMO. Complex de novo
rearrangement of chromosome 9 with clinical features of monosomy 9p syndrome.
Clin Genet 1979;16:151-5.
37 Hoo JJ, Fischer A, Furhmann W. Familial tiny 9p/20p transloca-tion:
9p24 the critical segment for monosomy 9p syndrome. Ann Genet (Paris)
38 Hoo JJ. Karyotype phenotype analysis: 9p deletion versus 10q2
duplication. Ann Genet (Paris) 1986;29:266-8.
39 Howard-Peebles PN, Goldsmith JP. Duplication of region 2q31?2qter
in a family with 2/9 translocation. Hum Genet 1980;20:84-8.
40 Jones LA, Jordan DK, Taysi K, et al. Partial duplication of the
long arm of chromosome 5: a case due to balanced paternal translocation and
review of the literature. Hum Genet 1979;51:37-42.
41 Jotterand M, Juillard E. A new case of trisomy for the distal part
of 13q due to maternal translocation, t(9;13)(p21;q21). Hum Genet
42 Junien C, Despoisse S, Turleau C, et al. Assignment of
phosphoglycerate mutase (PGAMA) to human chromosome 10. Regional mapping of
GOTI and PGAMA to subbands 10q26.1 (or q25.3). Ann Genet (Paris)
43 Kadotani T, Watanabe Y, Kiyuna T, Takeuchi S. A case of partial
trisomy 4q resulting from familial (4;9)(q23;p24) trans-location. Proc Japan
44 Liberfarb RM, Atkins L, Holmes LB. A clinical syndrome associated
with 5p duplication and 9p deletion. Ann Genet (Paris) 1980;23:26-30.
45 Monteleone P, Monteleone J, Sekhon G, et al. Partial trisomy 5 with
a carrier parent t(5p-;9p+). Clin Genet 1976;9:437-40.
46 Müke J, Trautmann U, Sanding KR, Theile H. The crucial band for
phenotype of Irisomy 18. Hum Genet 1982,60:205.
47 Orye E, Verhaaren H, Van den Bogaert-Van Heesvelde AM. The 9p-
deletion syndrome. Report of a patient with a 46,XX,9p- constitution due to a
paternal t(9p;15q+) trans-location. Clin Genet 1975 ;8:349-57.
48 Pratt NR, Bulugahapitiya DTD. Partial trisomy 12q; a clinically
recognisable syndrome. Genetic risks associated with transloca-tions of
chromosome 12q. J Med Genet 1983;20:86-9.
49 Prieto F, Badia L, Ascnsi F, Roques V. Two reciprocal
translocations t(9p+;13q) and t(13q-;21q+): a study of the families. Hum Genet
50 Rosenthal IM, Beligere N, Thompson F, et al. Trisomy of the distal
portion of the long arm of chromosome 2, a new familial syndrome associated
with mental retardation and characteristic facies. Am J Med Genet
51 Schinzel A, Hayashi K, Schmid W. Further delineation of the
clinical picture of trisomy for the distal segment of chromosome 13: report of
three cases. Hum Genet 1976;32:1-12.
52 Sekhon GS, Taysi K. Concordant congenital malformations in twins
with inherited translocation: t(9p-;13q+). Hum Genet 1979;50:271-6.
53 Steinbach P, Adkins WN, Caspar H, Dumar KW, et al. The dup (3p)
syndrome: report of eight cases and review of the literature. Am J Med Genet
54 Zabel B, Baumann W. Partial trisomy 12q. J Med Genet
55 Rethoré MO, Dutrillaux B, Baheux G, Gerveaux J, Lejeune J.
Monosomie pour les régions juxtacentrométriques d'un chromo-some 21. Exp Cell
56 Rethoré MO. In: Yunis JJ, ed. New chromosomal syndromes. New York:
Academic Press, 1977:154-7.
57 Rethoré MO. Chromosome deletion and ring chromosome syndromes. In:
Vinken PJ, Bruyn GW, eds. Congenital mal-formations of the brain and skull.
Chap 12: Handbook of clinical neurology vol 31. Amsterdam: North-Holland,
58 Huret JL, Delabar JM, Marlhens F, et al. Down syndrome with
duplication of a region of chromosome 21 containing the CuZn superoxide
dismutase gene without detectable karyotypic abnormality. Hum Genet