American Journal of Medical Genetics 4418-23 (1992)
7p Deletion Syndrome: An Adult With Mild Manifestations Theresa A. Grebe, Mark A. Stevens, Karen Byrne-Essif, and Suzanne B. Cassidy Section of GeneticslDysmorphology and Steele Memorial Children’s Research Center, Department of Pediatrics (T.A.G., K.B.-E.,S.B.C.) and Cytogenetics Laboratory, Department of Pathology (M.A.S.), University of Arizonn, Tucson
Deletion of 7p results in a wide spectrum of congenital abnormalities and minor facial and hand anomalies, often including craniosynostosis. We report on the oldest recognized patient with this disorder, a 24-year-old woman with an interstitial deletion from p15.3-p21.2 or p21.3. The manifestations in this patient are milder than those of previously described patients, and include borderline mental retardation, short stature, minor facial anomalies, and severa1 skeletal changes. The absence of craniosynostosis in this patient is noteworthy, given previous sug gestions that there is a specific locus for this finding in the 7p region. Twelve cases of 7p deletion, in which the missing segment overlaps that of the current case, are reviewed. This case delineates a broader spectrum for patients with 7p deletion syndrome. O 1992 Wiley-Liss, Inc.
KEY WORDS chromosome 7p, craniosynostosis, deletion, dysmorphic, mental retardation, short stature, skeletal anomalies INTRODUCTION Partial deletion of 7p has been reported over 20 times and results in a wide spectrum of congenital anomalies. This variability is due, in part, to interpatient differences in the location and size of the deletion. Craniosynostosis, an uncommon finding in aneuploidy syndromes, is often seen in the 7p deletion syndrome. We evaluated an instructive patient with del 7p whose manifestations were milder than previously reported, including absence of craniosynostosis. Received for publication June 28,1991; revision received February 3, 1992. Address reprint requests to Dr. Suzanne B. Cassidy, Department of Pediatrics, Section of GeneticsíDysmorphology, University of Arizona College of Medicine, Tucson, AZ 85724.
O 1992 Wiley-Liss, Inc.
CLINICAL REPORT RC was referred for evaluation of minor anomalies. She was the product of a term pregnancy complicated only by poor weight gain in a 23-year-oldG2P1 woman. Delivery was unremarkable, with birth weight 3.2 kg (50th centile) and length 46 cm (5th-10th centile). She was noted at birth to have a number of abnormalities, including a “prow-shaped forehead and ptosis of the left eyelid, features which persisted (Fig. 1). She failed to thrive for the first 3 months. Developmentally she was slightly delayed, walking first a t 16 months, and talking a t approximately 2 years. She attended special education classes from the second grade on, and her IQ was said to be 70. An umbilical hernia was repaired at age 4,and her ptosis was improved surgically at age 7. Laboratory evaluation for short stature at age 7 years showed the following results to be normal: complete blood count, urinalysis, serum calcium, phosphorus, alkaline phosphatase, serum electrolytes, glucose, thyroid function tests, prolactin, FSH, LH, SMA-20, and IVP. Bone age was determined to be 6 years a t a chronological age of 7-10/12 years. This was thought to be consistent with the diagnosis of constitutional growth delay. Formal ophthalmologic evaluation at age 9 years revealed high hyperopia, left blepharophimosis, and normal fundus exam. Follow-up ophthalmologic evaluation at age 24 years revealed mild hyperopia. Hearing evaluation at age 9 was normal. Menses began at 14 years and have remained irregular. She underwent surgery for patellofemoral instability at age 24. On physical exam a t age 24 years, her height was (5th centile (146 cm) and height-age 11 years; weight was at the 30th centile (53 kg), and OFC was between the 2nd and 5th centiles. She had a short forehead with a low hairline and a prominent glabella (Fig. 2). Hypertelorism, telecanthus, short downslanting palpebral fissures, and epicanthal folds were present. The nose was large, with a broad, prominent bridge, and a short, poorly grooved philtrum with indistinct markings. The mouth was wide, with a high-arched palate, and absence of the left lateral incisor. The ears were short, but normally formed. The neck was short, with a low posterior hairline. She had a nevus flammeus on the glabella and
19
Fig. 1. a,b: The patient at birth and age 3-1/2 years.
posterior neck. The thorax was asymmetrical with prominence of the left side of the sternum and narrow shoulders. Cardiac auscultation was normal. Sexual development was Tanner Stage V. She had an unusual suprasacral fat mass. Brachydactyly was present (Fig. 3) with short fourth and fifth metacarpals and hypoplastic interphalangeal creases with that of the fifth finger missing entirely. The hypothenar eminence was hypoplastic, and the palmar creases were abnormal and also hypoplastic. She had cutaneous webbing of the second and third fingers. The joints of the hand were prominent. Dermatoglyphic analysis revealed the presence of nine fingertip arches and one ulnar loop (right 3rd finger), with an open field pattern on the palms, bilaterally. Metacarpophalangeal profile analysis (Fig. 4) confirms the clinical observation of small hands with
Fig. 2. a,b The patient at age 24 years.
short phalanges. Her feet were small, measuring less than the 3rd centile, with mild cutaneous 2-3 syndactyly, and short halluces with short metatarsals. Radiographs documented a number of skeletal abnormalities, including a lacunar appearance to the skull, a demineralized sella turcica, an abnormal C-3 neural arch of the spine, and fusion anomalies of the second and third ribs bilaterally. No craniosynostosis was seen. Cardiac silhouette was normal. She had had a benign
20
Grebe et al.
Fig. 3. a,b "he patient's hands at age 24 years.
Metacarpophalangeal Profile
shallow orbits/proptosis (51121, abnormalities of bone mineralization or formation (4/12),up- or down-slanting 75 palpebral fissures (5/12), flat or depressed nasal bridge E 4 (5/12), and cardiac defects (5/12). These findings are summarized in Figure 6. Our patient manifested a milder phenotype than those previously reported, as evidenced by the presence of only half of the common findings (abnormal head shape, developmental delay/MR, hand anomalies, short stature, abnormalities of bone mineralization or formai tion, and down-slanting palpebral fissures). Although 1 2 3 4 5 , ) 2 3 4 5,,2 3 4 5,,i 2 3 4 5 the patient had many other minor anomalies, no major 'Metacarpai" Proximal Middle Dista1 malformations were present. An interesting comparison Fig. 4. Metacarpophalangeal profile analysis of the patient (cour- can be made with the case reported by Moedjono et al. tesy of Dr. Merlin Butler.) [19781.That patient had a similar mild phenotype with borderline microcephaly, dull normal intelligence, short broad neck with low posterior hairline, mild camptodaccortical defect of the right radius noted at age 9 which tyly, and a PDA, yet had a deletion of 7p14. The deletion in that case apparently does not overlap with that seen was no longer present. On prometaphase chromosome analysis she was in our patient; however, restudy of that patient with or higher resolution techniques would be of interest in found to have a de novo 46,XX,de1(7)(~15.3-~21.2 light of clinical similarities. p21.3) (Fig. 5). The absence of craniosynostosis in our patient is noteDISCUSSION worthy. Fryns et al. [1985] stated that deletion of the ñeview of 26 reported cases of del 7p syndrome in- distal 7p22 band is necessary and sufficient for premacluded 12 cases in which the deletion overlapped the ture closure of the cranial sutures. This was later reportion missing in our patient (Table 1). The deletions in futed by Motegi et al. [19851 and Garcia-Esquive1et al. these cases spanned between p13 and pter. One other 119861, who reported cases of distal deletions including case, reported by Wilson et al. [19731, had a 46,XX, band 7p21.2 with preservation of 7p22 in which cranit(7p-;13s+) karyotype; it was not included in this osynostosis was present. Bianchi et al. [1981] suggested review since the technical limitation of the chromosome that deletion of 7p13-pl5, in contrast to more distal analysis did not allow determination of whether the deletions at 7p22, is not associated with cranipatient had a balanced translocation or a true deletion of osynostosis. This statement was recently called into chromosome 7. Owing to the wide variability in the question by Aughton et al. [19911, who reported a padeleted segment among reported patients, an accurate tient with an interstitial deletion of 7p13-pl5 who nevdelineation of the syndrome has not yet been possible; ertheless had craniosynostosis. Severa1 other previous however, certain manifestations in this group with over- reports suggested that the critica1 segment for cranilapping deletions are prominent. These include abnor- osynostosis lies distal to band 7p21 [Garcia-Esquive1et mal head shape (11/12), developmental delay/MR al., 1986; Motegi et al., 1985; Schomig-Springler et al., (10/12),apparently low-set and/or posteriorly angulated 19863. Speleman et al. [19891then proposed that deleears (8/12), genital anomalies (8/12), hand anomalies tion of 7p21.1-p21.2is compatible with craniosynostosis. (10/12), craniosynostosis (6/12), short stature (7/12), Our case refutes this conclusion because a deletion of
q
71
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,
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,
,
,
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,
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,
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Deleted segment Age ( Y k x Developmental delay/MR Short stature Cranium Craniosynostosis Abnormal shape Eyes Up-idown-slanting palpebral fissures Shallow orbitsi proptosis Nose Depressed nasal bridge Broad nasal root Ears Abnormal shape or position Cardiac defects Urogenital anomalies Hands Aberrant palmar creaaes Short handsifingers Other anomalies Feet Talipes equinovarus Other Limited joint extension Sacra1 dimple Abnormalities of bone mineralization'formation Anal atresia
-
p p
Present report
-
+ +
+ +
+
+
-
-
+ +
+ + +
+
+
+
-
+
Riedrich et al 119751 p21-22 NB/F
Schomig Spingler et _ _ al [19861 p21-pter NB'IF ?
+
Dhadial and Smith U9791 pl5.2-pter 3/12/F McPherson et al [19761
TABLE 1. Comparison of Clinical Findings in 7p Deletion Syndrome Motegi et al [19851
Garcia-Esquive1 [19861-..pp
5 12 -
5:12
+
+
~
I
-
4 12 2 12
3'12 2'12 ~
+
+
~
~
4/12 7/12
5:12
8;12
5/12
-
+
-
8;12
5,12
+
+
5/12
+
5 12
6Í12 11 12 -
10,12 7/12
Frexuency
-
+
+
~
+
7
p13-15 2/12/F
-
+
+
+ +
~
Bianchi et al-. íi981> p13-15 6/12/F
+
~
t
+
+
~
+
~
~
~
t
+
~
+
+
p13-21 NBíF
Muller et a l [19811
~
+
-
~
+
+ +
t
~
~
+
~
+ +
p13-21 NBiM
p15-21 3/12/F ?
+
Crawfurd et al [19791
Miller e t al [1979)
22
Grebe et al. ~~
22 1 22 2 22 1 21 1 21 2 21.1 l i l
P
112
:5:
14 2 I4 I I7
12 1 122 12 I 11 2 I1 I
II I I 1 21
I I 22
11 2 1
21 I I 21 12 21 I? 21 2 21 7 22 I
q
22 2 22 7 71.1
31 2 11 11
71 72 ? I 17 12 I 72.2 32 7
17 74 ??
76 I
Fig. 5. Chromosome 7 ISCN idiogram a t the 850 band level is shown on the left. Three chromosome 7 pairs from the patient a t the 850 band level are on the right, showing a deletion of (~15.3-p21.2 or p21.3) in the right hand member of each pair. p15.2 is indicated for comparison purposes.
Abnormal head shape
DDlMR Hand anomalles
1
-
Abnormal ears Urogenital anomalies Short siaiure Cranlosynostosis
Cardiac defects Bone abnormalities.
0%
20%
40%
60%
80%
100%
*Abnormal bone m i n e r a l ~ z a . t ~ o n l f o r m ~ t ~ o " **PalpebraI fissures
Fig. 6. Common clinical findings in 12 patients with deletions including 7p15.3-p21.2
7p Deletion Syndrome
bands 7p21.1-p21.2 is present, yet the patient does not have craniosynostosis. Because no consistent deletion of chromosome 7p can be implicated as a cause of craniosynostosis, we can speculate that the occurrence of premature closure of the cranial sutures is likely to require more than one abnormal factor. Determination of the relation of 7p deletion syndrome to craniosynostosis will likely await molecular genetic analysis. This patient's mild clinical findings, lack of craniosynostosis, and older age make this case of 7p- syndrome noteworthy. The findings in this patient also emphasize the broadness of the clinical spectrum of the 7p- syndrome. This case illustrates the need for continuing delineation of the phenotypic consequences and natural history of chromosomal abnormalities, and reinforces the value of chromosomal studies in any patient with borderline mental retardation and mildly dysmorphic features.
ACKNOWLEDGMENTS The authors are very grateful to the patient and her family for their willing cooperation with reporting RC. We greatly appreciate the efforts of members of the University of Arizona Health Sciences Cytogenetics Laboratory in the preparation and interpretation of the karyotypes and of Dr. Merlin Butler (Vanderbilt University) for doing the metacarpophalangeal profile analysis. We also thank Maryann Wagner for assistance with manuscript preparation. Dr. Grebe was supported by a Robert S.Flinn General Medicine-Career Development Fellowship. REFERENCES Aughton DJ, Cassidy SB, Whiteman DAH, Delach JA, Guttmacher AE (1991): Brief clinical report: Chromosome 7p - syndrome: crani-
23
osynostosis with preservation of region 7p2. Am J Med Genet 40:440-443. Bianchi DW, Cirillo-Silengo M, Luzzati L, Greenstein RM (1981): Interstitial deletion of the short arm of chromosome 7 without craniosynostosis. Clin Genet 19:456-461. Crawfurd Md'A, Kessel 1, Liberman M, McKeow JA, Mandailia PY, Ridler MAC (1979): Partial monosomy 7 with interstitial deletions in two infants with differing congenital anomalies. J Med Genet 16453-460. Dhadial RK, Smith MF (1979):Terminal 7p deletion and 1;7translocation associated with craniosynostosis. Hum Genet 50:285-289. Friedrich U, Lyngbye T, 0ster J (1975): A girl with karyotype 46,XX,de1(7)(qter-p15:).Humangenetik 26:161-165. Fryns J P , Hespeslagh M, Agneessen SA, Van den Berghe H (1985): De novo partial 2p3 trisomy/distal 7p22 monosomy in a malformed newborn with 7p deletion phenotype and craniosynostosis. Ann Genet 28(1):45-46. Garcia-Esquive1L,Garcia-Cruz D, Rivera H, Plascencia ML, Cantú J M (1986): De novo del(7)(pter-p21.1::p15.2-qter)and craniosynostosis. Ann Genet 29:36-38. McPherson E, Hall JG, Hickman R, Gong BT, Norwood TH, Hoehn H (1976): Chromosome 7 short arm deletion and craniosynostosis: A 7p- syndrome. Hum Genet 35117-123. Miller M, Kaufman G, Reed G, Bilenker R, Schinzel A (1979): Familial, balanced insertional translocation of chromosome 7 leading to offspring with deletion and duplication of the inserted segment, 7p15-7p21. Am J Med Genet 4:323-332. MoedjonoSI,Funderburk SJ,SparkesRS (1978): Chromosome 7 shortarm interstitial deletion ( ~ 1 4 )Hum . Genet 44:51-57. Motegi T, Ohuchi M, Ohtaki C, Fujiwara K, Enomoto S, Hasegawa T, Kishi K, Hayakawa H (1985): Craniosynostosis in a boy with de1(7)(p15.3p21.3):Assignment by deletion mapping of the critica1 . Genet segment for craniosynostosis to the mid-portion of 7 ~ 2 1Hum 71:160-162. Müller U, Staudt F, Hameister H (1981): A patient with interstitial deletion 7(p13-p21). Ann Genet 24:239-241. Schomig-SpinglerM, Schmid M, Grimm T (1986): Chromosome 7 short arm deletion, 7p21-pter. Hum Genet 74:323-325. Speleman F, Craen M, Leroy J (1989): De novo terminal deletion 7~22.1-pterin a child without craniosynostosis. J Med Genet 26528-532. Wilson MG, Fujimoto A, Shinno NW, Towner JW (1973): Giant satellites or translocation? Cytogenet Cell Genet 12:209-214.
7p Deletion Syndrome: An Adult With Mild Manifestations Theresa A. Grebe, Mark A. Stevens, Karen Byrne-Essif, and Suzanne B. Cassidy Section of GeneticslDysmorphology and Steele Memorial Children’s Research Center, Department of Pediatrics (T.A.G., K.B.-E.,S.B.C.) and Cytogenetics Laboratory, Department of Pathology (M.A.S.), University of Arizonn, Tucson
Deletion of 7p results in a wide spectrum of congenital abnormalities and minor facial and hand anomalies, often including craniosynostosis. We report on the oldest recognized patient with this disorder, a 24-year-old woman with an interstitial deletion from p15.3-p21.2 or p21.3. The manifestations in this patient are milder than those of previously described patients, and include borderline mental retardation, short stature, minor facial anomalies, and severa1 skeletal changes. The absence of craniosynostosis in this patient is noteworthy, given previous sug gestions that there is a specific locus for this finding in the 7p region. Twelve cases of 7p deletion, in which the missing segment overlaps that of the current case, are reviewed. This case delineates a broader spectrum for patients with 7p deletion syndrome. O 1992 Wiley-Liss, Inc.
KEY WORDS chromosome 7p, craniosynostosis, deletion, dysmorphic, mental retardation, short stature, skeletal anomalies INTRODUCTION Partial deletion of 7p has been reported over 20 times and results in a wide spectrum of congenital anomalies. This variability is due, in part, to interpatient differences in the location and size of the deletion. Craniosynostosis, an uncommon finding in aneuploidy syndromes, is often seen in the 7p deletion syndrome. We evaluated an instructive patient with del 7p whose manifestations were milder than previously reported, including absence of craniosynostosis. Received for publication June 28,1991; revision received February 3, 1992. Address reprint requests to Dr. Suzanne B. Cassidy, Department of Pediatrics, Section of GeneticsíDysmorphology, University of Arizona College of Medicine, Tucson, AZ 85724.
O 1992 Wiley-Liss, Inc.
CLINICAL REPORT RC was referred for evaluation of minor anomalies. She was the product of a term pregnancy complicated only by poor weight gain in a 23-year-oldG2P1 woman. Delivery was unremarkable, with birth weight 3.2 kg (50th centile) and length 46 cm (5th-10th centile). She was noted at birth to have a number of abnormalities, including a “prow-shaped forehead and ptosis of the left eyelid, features which persisted (Fig. 1). She failed to thrive for the first 3 months. Developmentally she was slightly delayed, walking first a t 16 months, and talking a t approximately 2 years. She attended special education classes from the second grade on, and her IQ was said to be 70. An umbilical hernia was repaired at age 4,and her ptosis was improved surgically at age 7. Laboratory evaluation for short stature at age 7 years showed the following results to be normal: complete blood count, urinalysis, serum calcium, phosphorus, alkaline phosphatase, serum electrolytes, glucose, thyroid function tests, prolactin, FSH, LH, SMA-20, and IVP. Bone age was determined to be 6 years a t a chronological age of 7-10/12 years. This was thought to be consistent with the diagnosis of constitutional growth delay. Formal ophthalmologic evaluation at age 9 years revealed high hyperopia, left blepharophimosis, and normal fundus exam. Follow-up ophthalmologic evaluation at age 24 years revealed mild hyperopia. Hearing evaluation at age 9 was normal. Menses began at 14 years and have remained irregular. She underwent surgery for patellofemoral instability at age 24. On physical exam a t age 24 years, her height was (5th centile (146 cm) and height-age 11 years; weight was at the 30th centile (53 kg), and OFC was between the 2nd and 5th centiles. She had a short forehead with a low hairline and a prominent glabella (Fig. 2). Hypertelorism, telecanthus, short downslanting palpebral fissures, and epicanthal folds were present. The nose was large, with a broad, prominent bridge, and a short, poorly grooved philtrum with indistinct markings. The mouth was wide, with a high-arched palate, and absence of the left lateral incisor. The ears were short, but normally formed. The neck was short, with a low posterior hairline. She had a nevus flammeus on the glabella and
19
Fig. 1. a,b: The patient at birth and age 3-1/2 years.
posterior neck. The thorax was asymmetrical with prominence of the left side of the sternum and narrow shoulders. Cardiac auscultation was normal. Sexual development was Tanner Stage V. She had an unusual suprasacral fat mass. Brachydactyly was present (Fig. 3) with short fourth and fifth metacarpals and hypoplastic interphalangeal creases with that of the fifth finger missing entirely. The hypothenar eminence was hypoplastic, and the palmar creases were abnormal and also hypoplastic. She had cutaneous webbing of the second and third fingers. The joints of the hand were prominent. Dermatoglyphic analysis revealed the presence of nine fingertip arches and one ulnar loop (right 3rd finger), with an open field pattern on the palms, bilaterally. Metacarpophalangeal profile analysis (Fig. 4) confirms the clinical observation of small hands with
Fig. 2. a,b The patient at age 24 years.
short phalanges. Her feet were small, measuring less than the 3rd centile, with mild cutaneous 2-3 syndactyly, and short halluces with short metatarsals. Radiographs documented a number of skeletal abnormalities, including a lacunar appearance to the skull, a demineralized sella turcica, an abnormal C-3 neural arch of the spine, and fusion anomalies of the second and third ribs bilaterally. No craniosynostosis was seen. Cardiac silhouette was normal. She had had a benign
20
Grebe et al.
Fig. 3. a,b "he patient's hands at age 24 years.
Metacarpophalangeal Profile
shallow orbits/proptosis (51121, abnormalities of bone mineralization or formation (4/12),up- or down-slanting 75 palpebral fissures (5/12), flat or depressed nasal bridge E 4 (5/12), and cardiac defects (5/12). These findings are summarized in Figure 6. Our patient manifested a milder phenotype than those previously reported, as evidenced by the presence of only half of the common findings (abnormal head shape, developmental delay/MR, hand anomalies, short stature, abnormalities of bone mineralization or formai tion, and down-slanting palpebral fissures). Although 1 2 3 4 5 , ) 2 3 4 5,,2 3 4 5,,i 2 3 4 5 the patient had many other minor anomalies, no major 'Metacarpai" Proximal Middle Dista1 malformations were present. An interesting comparison Fig. 4. Metacarpophalangeal profile analysis of the patient (cour- can be made with the case reported by Moedjono et al. tesy of Dr. Merlin Butler.) [19781.That patient had a similar mild phenotype with borderline microcephaly, dull normal intelligence, short broad neck with low posterior hairline, mild camptodaccortical defect of the right radius noted at age 9 which tyly, and a PDA, yet had a deletion of 7p14. The deletion in that case apparently does not overlap with that seen was no longer present. On prometaphase chromosome analysis she was in our patient; however, restudy of that patient with or higher resolution techniques would be of interest in found to have a de novo 46,XX,de1(7)(~15.3-~21.2 light of clinical similarities. p21.3) (Fig. 5). The absence of craniosynostosis in our patient is noteDISCUSSION worthy. Fryns et al. [1985] stated that deletion of the ñeview of 26 reported cases of del 7p syndrome in- distal 7p22 band is necessary and sufficient for premacluded 12 cases in which the deletion overlapped the ture closure of the cranial sutures. This was later reportion missing in our patient (Table 1). The deletions in futed by Motegi et al. [19851 and Garcia-Esquive1et al. these cases spanned between p13 and pter. One other 119861, who reported cases of distal deletions including case, reported by Wilson et al. [19731, had a 46,XX, band 7p21.2 with preservation of 7p22 in which cranit(7p-;13s+) karyotype; it was not included in this osynostosis was present. Bianchi et al. [1981] suggested review since the technical limitation of the chromosome that deletion of 7p13-pl5, in contrast to more distal analysis did not allow determination of whether the deletions at 7p22, is not associated with cranipatient had a balanced translocation or a true deletion of osynostosis. This statement was recently called into chromosome 7. Owing to the wide variability in the question by Aughton et al. [19911, who reported a padeleted segment among reported patients, an accurate tient with an interstitial deletion of 7p13-pl5 who nevdelineation of the syndrome has not yet been possible; ertheless had craniosynostosis. Severa1 other previous however, certain manifestations in this group with over- reports suggested that the critica1 segment for cranilapping deletions are prominent. These include abnor- osynostosis lies distal to band 7p21 [Garcia-Esquive1et mal head shape (11/12), developmental delay/MR al., 1986; Motegi et al., 1985; Schomig-Springler et al., (10/12),apparently low-set and/or posteriorly angulated 19863. Speleman et al. [19891then proposed that deleears (8/12), genital anomalies (8/12), hand anomalies tion of 7p21.1-p21.2is compatible with craniosynostosis. (10/12), craniosynostosis (6/12), short stature (7/12), Our case refutes this conclusion because a deletion of
q
71
-
~
o Right Hand Left Hand
!
,
,
,
,
,
,
,
,
,
,
,
,
"
,
,
,
,
,
1
"
~
'NB, newborn.
Deleted segment Age ( Y k x Developmental delay/MR Short stature Cranium Craniosynostosis Abnormal shape Eyes Up-idown-slanting palpebral fissures Shallow orbitsi proptosis Nose Depressed nasal bridge Broad nasal root Ears Abnormal shape or position Cardiac defects Urogenital anomalies Hands Aberrant palmar creaaes Short handsifingers Other anomalies Feet Talipes equinovarus Other Limited joint extension Sacra1 dimple Abnormalities of bone mineralization'formation Anal atresia
-
p p
Present report
-
+ +
+ +
+
+
-
-
+ +
+ + +
+
+
+
-
+
Riedrich et al 119751 p21-22 NB/F
Schomig Spingler et _ _ al [19861 p21-pter NB'IF ?
+
Dhadial and Smith U9791 pl5.2-pter 3/12/F McPherson et al [19761
TABLE 1. Comparison of Clinical Findings in 7p Deletion Syndrome Motegi et al [19851
Garcia-Esquive1 [19861-..pp
5 12 -
5:12
+
+
~
I
-
4 12 2 12
3'12 2'12 ~
+
+
~
~
4/12 7/12
5:12
8;12
5/12
-
+
-
8;12
5,12
+
+
5/12
+
5 12
6Í12 11 12 -
10,12 7/12
Frexuency
-
+
+
~
+
7
p13-15 2/12/F
-
+
+
+ +
~
Bianchi et al-. íi981> p13-15 6/12/F
+
~
t
+
+
~
+
~
~
~
t
+
~
+
+
p13-21 NBíF
Muller et a l [19811
~
+
-
~
+
+ +
t
~
~
+
~
+ +
p13-21 NBiM
p15-21 3/12/F ?
+
Crawfurd et al [19791
Miller e t al [1979)
22
Grebe et al. ~~
22 1 22 2 22 1 21 1 21 2 21.1 l i l
P
112
:5:
14 2 I4 I I7
12 1 122 12 I 11 2 I1 I
II I I 1 21
I I 22
11 2 1
21 I I 21 12 21 I? 21 2 21 7 22 I
q
22 2 22 7 71.1
31 2 11 11
71 72 ? I 17 12 I 72.2 32 7
17 74 ??
76 I
Fig. 5. Chromosome 7 ISCN idiogram a t the 850 band level is shown on the left. Three chromosome 7 pairs from the patient a t the 850 band level are on the right, showing a deletion of (~15.3-p21.2 or p21.3) in the right hand member of each pair. p15.2 is indicated for comparison purposes.
Abnormal head shape
DDlMR Hand anomalles
1
-
Abnormal ears Urogenital anomalies Short siaiure Cranlosynostosis
Cardiac defects Bone abnormalities.
0%
20%
40%
60%
80%
100%
*Abnormal bone m i n e r a l ~ z a . t ~ o n l f o r m ~ t ~ o " **PalpebraI fissures
Fig. 6. Common clinical findings in 12 patients with deletions including 7p15.3-p21.2
7p Deletion Syndrome
bands 7p21.1-p21.2 is present, yet the patient does not have craniosynostosis. Because no consistent deletion of chromosome 7p can be implicated as a cause of craniosynostosis, we can speculate that the occurrence of premature closure of the cranial sutures is likely to require more than one abnormal factor. Determination of the relation of 7p deletion syndrome to craniosynostosis will likely await molecular genetic analysis. This patient's mild clinical findings, lack of craniosynostosis, and older age make this case of 7p- syndrome noteworthy. The findings in this patient also emphasize the broadness of the clinical spectrum of the 7p- syndrome. This case illustrates the need for continuing delineation of the phenotypic consequences and natural history of chromosomal abnormalities, and reinforces the value of chromosomal studies in any patient with borderline mental retardation and mildly dysmorphic features.
ACKNOWLEDGMENTS The authors are very grateful to the patient and her family for their willing cooperation with reporting RC. We greatly appreciate the efforts of members of the University of Arizona Health Sciences Cytogenetics Laboratory in the preparation and interpretation of the karyotypes and of Dr. Merlin Butler (Vanderbilt University) for doing the metacarpophalangeal profile analysis. We also thank Maryann Wagner for assistance with manuscript preparation. Dr. Grebe was supported by a Robert S.Flinn General Medicine-Career Development Fellowship. REFERENCES Aughton DJ, Cassidy SB, Whiteman DAH, Delach JA, Guttmacher AE (1991): Brief clinical report: Chromosome 7p - syndrome: crani-
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osynostosis with preservation of region 7p2. Am J Med Genet 40:440-443. Bianchi DW, Cirillo-Silengo M, Luzzati L, Greenstein RM (1981): Interstitial deletion of the short arm of chromosome 7 without craniosynostosis. Clin Genet 19:456-461. Crawfurd Md'A, Kessel 1, Liberman M, McKeow JA, Mandailia PY, Ridler MAC (1979): Partial monosomy 7 with interstitial deletions in two infants with differing congenital anomalies. J Med Genet 16453-460. Dhadial RK, Smith MF (1979):Terminal 7p deletion and 1;7translocation associated with craniosynostosis. Hum Genet 50:285-289. Friedrich U, Lyngbye T, 0ster J (1975): A girl with karyotype 46,XX,de1(7)(qter-p15:).Humangenetik 26:161-165. Fryns J P , Hespeslagh M, Agneessen SA, Van den Berghe H (1985): De novo partial 2p3 trisomy/distal 7p22 monosomy in a malformed newborn with 7p deletion phenotype and craniosynostosis. Ann Genet 28(1):45-46. Garcia-Esquive1L,Garcia-Cruz D, Rivera H, Plascencia ML, Cantú J M (1986): De novo del(7)(pter-p21.1::p15.2-qter)and craniosynostosis. Ann Genet 29:36-38. McPherson E, Hall JG, Hickman R, Gong BT, Norwood TH, Hoehn H (1976): Chromosome 7 short arm deletion and craniosynostosis: A 7p- syndrome. Hum Genet 35117-123. Miller M, Kaufman G, Reed G, Bilenker R, Schinzel A (1979): Familial, balanced insertional translocation of chromosome 7 leading to offspring with deletion and duplication of the inserted segment, 7p15-7p21. Am J Med Genet 4:323-332. MoedjonoSI,Funderburk SJ,SparkesRS (1978): Chromosome 7 shortarm interstitial deletion ( ~ 1 4 )Hum . Genet 44:51-57. Motegi T, Ohuchi M, Ohtaki C, Fujiwara K, Enomoto S, Hasegawa T, Kishi K, Hayakawa H (1985): Craniosynostosis in a boy with de1(7)(p15.3p21.3):Assignment by deletion mapping of the critica1 . Genet segment for craniosynostosis to the mid-portion of 7 ~ 2 1Hum 71:160-162. Müller U, Staudt F, Hameister H (1981): A patient with interstitial deletion 7(p13-p21). Ann Genet 24:239-241. Schomig-SpinglerM, Schmid M, Grimm T (1986): Chromosome 7 short arm deletion, 7p21-pter. Hum Genet 74:323-325. Speleman F, Craen M, Leroy J (1989): De novo terminal deletion 7~22.1-pterin a child without craniosynostosis. J Med Genet 26528-532. Wilson MG, Fujimoto A, Shinno NW, Towner JW (1973): Giant satellites or translocation? Cytogenet Cell Genet 12:209-214.
