Hum Genet (1991) 87:452-456

9 Springer-Verlag1991

Greig syndrome associated with an interstitial deletion of 7p: confirmation of the localization of Greig syndrome to 7p13 Anjana Lal Pettigrew 1' :, Frank Greenberg 1, C.Thomas Caskey l' 3, and David H. Leflbetter t 1Institute for Molecular Genetics, Baylor College of Medicine, Houston, Texas, USA 2Departments of Pathology, Pediatrics and Obstetrics-Gynecology, University of Kentucky College of Medicine, Lexington, Kentucky, USA 3Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas, USA Received October 8, 1990 / Revised December 26, 1990

Summary. A n 11-month-old infant with Greig cephalopolysyndactyly syndrome and mild developmental delay is described. High-resolution c h r o m o s o m a l analysis showed a de novo interstitial deletion of c h r o m o s o m e 7p with breakpoints located at p13 and p14. Cytogenetic analysis of polymorphisms of the heterochromatin in the pericentromeric region suggested the deleted chromosome was of paternal origin. This case confirms the localization of Greig syndrome to 7p13 and emphasizes the importance of performing cytogenetic studies on patients with Mendelian disorders who have unusual findings or cognitive abnormalities in a disorder usually associated with normal intellect. Review of clinical features in published reports of patients with a deletion involving 7p13 showed a n u m b e r to have features overlapping with Greig syndrome. Because of this, we suggest that cytogenetic aberrations, particularly chromosomal microdeletions, m a y represent a significant etiology for Greig syndrome.

pressivity. Two families with dominantly inherited Greig syndrome segregating with balanced translocations involving 7p13[(t(3;7) and t(6;7)] have been reported ( T o m m e r u p and Nielsen 1983; Krfiger et al. 1989; Pelz et al. 1986). Recently, two patients with presumably sporadic Greig syndrome and atypical, severe psychom o t o r retardation have been reported (Rosenkranz et al. 1989; Wagner et al. 1990). One had a de novo unbalanced translocation associated with loss of chromosomal material between 7p11.2 and 7p13, and the other had a de novo del(7)(p12.3p14.2). We now report another sporadic case with typical clinical findings of Greig syndrome and mild developmental delay associated with an interstitial deletion of 7p, del(7)(p13p14), confirming the localization of Greig syndrome to 7p13. This suggests that the etiology of Greig cephalopolysyndactyly syndrome is at least sometimes chromosomal and may prove to be another microdeletion syndrome.

Case report Introduction Greig cephalopolysyndactyly syndrome is a disorder characterized by postaxial polydactyly of the hands (frequently pedunculated postminimus), broad or occasionally bifid thumbs, preaxial polydactyly of the feet, broad halluces, syndactyly of the fingers or toes, macrocephaly, frontal bossing, hypertelorism, and a broad nasal bridge (Gollop and Fontes 1985; Baraitser et al. 1983). Intelligence is usually normal, although a borderline I Q has been reported (Fryns et al. 1977; G n a m e y and Farriaux 1971; H o o t n i c k and H o l m e s 1972). Advanced bone age, mild hydrocephalus, craniosynostosis, and agenesis of the corpus callosum are occasional abnormalities. Although as m a n y as six sporadic cases of the disorder have been observed, the majority of cases reported have b e e n familial with an autosomal dominant m o d e of inheritance, high penetrance and variable exOffprint requests to: A.L. Pettigrew, Department of Pathology, University of Kentucky College of Medicine, 800 Rose Street, Lexington, KY 40536-0093, USA

The proband, an ll-month-old girl, was referred for evaluation of congenital anomalies of the hands and feet and suspected developmental delay. She was the third child of healthy, unrelated parents. The mother was age 30, and the father was age 31 at the time of her birth. She was born by vertex, vaginal delivery after a pregnancy complicated by premature labor at 32 weeks, which was successfully treated. Labor was induced at 39 weeks' gestation because of a maternal history of two previous large-for-gestational age infants and an estimated large fetal size by ultrasonography for this pregnancy. A fasting glucose at 7 months gestation was normal. The Apgar score was 9 at 1 and 5 min. Birth weight was 4730g (50th centile for age 2 months) and length was 54.6cm (50th centile for age 1 month). At birth she was noted to have a pedunculated postminimus of the left hand, which was verified by X-ray (Fig. 1). Complete syndactyly between digits III and IV and partial syndactyly between digitis II and III on the left were present. Partial syndactyly was present between digits III and IV on the right. Bilateral preaxial polydactyly of the feet was present. X-rays demonstrated partial duplication of the right first metatarsal, a broad first metatarsal on the left and complete duplication of the first phalanx on the left (Fig. 1). Cutaneous syndactyly between toes I, II and III was present bilaterally. Operative procedures to release syndactyly of digits III and IV bilaterally and to amputate the great toes bilaterally were performed at age 10 months.

453

Fig.3A, B. CT scan at age 11 months. Note mild prominence of the lateral ventricles (A). There was no evidence of craniosynostosis or absence of the corpus callosum (B)

Fig. 1. A, B X-rays showed a pedunculated postminimus of the left hand and a broad distal phalanx of the thumbs. C, D Note bilateral preaxial hexadactyly of the feet. The right first metatarsal and proximal first phalanx were partially duplicated. The right distal first phalanx was duplicated. The left first proximal and distal phalanges were duplicated. The left first metatarsal was broad and abnormal in shape

logical examination was normal. Developmental evaluation using the Gesell Developmental Schedules showed her to have fine and gross motor skills at 28 weeks, language and personal-social skills at 28 to 32 weeks and adaptive functioning at 20 to 28 weeks with scatter to 40 weeks. The family history is negative for any hand or foot anomalies and for mental retardation. Skull X-rays did not demonstrate craniosynostosis. A C T scan of the brain showed open lambdoid, coronal and sagittal sutures, mild prominence of the cisterns and lateral ventricles, and no evidence of agenesis of the corpus callosum (Fig. 3). Recent testing at age 25 months showed her to have a developmental quotient of 87 on the Bayley scales of Infant Development and of 85 on the Vineland Adaptive Behavior Scales: Interview Edition.

Cytogenetic analysis

Fig. 2. The patient at age 9 months. Note the prominent forehead, epicanthal folds and wide, flattened nasal bridge

Chromosome preparations were made from phytohemagglutinin (PHA)-stimulated peripheral blood lymphocytes. Lymphocytes were cultured in RPMI 1640 with 10% fetal calf serum and harvested after 96 h. Metaphase chromosome preparations were trypsin-G banded. Interpretation of the proband's karyotype was 46,XX,del(7)(p13p14) (Fig. 4). Parental chromosomes were normal. Comparison of the polymorphic pericentromeric region of the patient and her parents suggested the deleted chromosome was paternal in origin. A lymphoblastoid cell line (GM 4# 10609A, Human Genetic Mutant Cell Repository, Camden, N.J.) was established on this patient.

Discussion When evaluated at age 11 months (47 weeks), her length was 77.1cm (90th centile), weight was 12.64kg (50th centile for age 30 months) and occipital-frontal circumference (OFC) was 49.7 cm (50th centile for age 4 years). Significant clinical findings included macrocephaly with frontal bossing, a slightly broad nasal bridge (canthus index 38.6), mild epicanthal folds bilaterally, anteverted nares with a small notch posteriorly, mild diastasis rectus, wellhealed umbilical and inguinal hernia scars and a slightly anteriorly displaced anus (Fig. 2). The thumbs were broad and flat bilaterally. Partial syndactyly between digits II and III on the left was present, and well-healed scars between digits III and IV bilaterally from the previous release procedures were evident. Syndaetyly between toes I, II, and III bilaterally was present. Well-healed surgical scars on the medial aspect of the great toes was seen. Her neuro-

T h e p a t i e n t described in this r e p o r t has typical findings of G r e i g c e p h a l o p o l y s y n d a c t y l y s y n d r o m e i n c l u d i n g characteristic craniofacial a n o m a l i e s , preaxial polydactyly of the feet, postaxial p o l y d a c t y l y of the h a n d s , a n d syndactyly. M a c r o s o m i a , p r e s e n t in this p a t i e n t , is n o t a f e a t u r e of G r e i g s y n d r o m e a n d is m o s t likely an u n r e lated familial trait. H e r two o l d e r siblings who are otherwise n o r m a l were also large at b i r t h a n d c o n t i n u e to b e large for their age. A l t h o u g h i n t e l l i g e n c e is u s u a l l y norm a l in this disorder, mild cognitive deficits h a v e occasionally b e e n r e p o r t e d . O u r p a t i e n t is n o w f u n c t i o n i n g i n

454

7p

Gamma-glutamylcyclotransferase Craniosynoslosis Interleukin 6 } Horneobox

• ..g o * o a

TCRG Inhibin beto A

PGAM2' I !" EGFR

Protein kinose. CAMPdependent, type I regulotory subunit

Fig, 4, A Three partial karyotypes of the patient with the deleted 7 on the left in each pair and the normal 7 on the right. Arrows pointing to diagrammatic chromosome 7 denote breakpoints of the

interstitial deletion (p13). B Partial karyotypes of chromosome 7 from the mother (left), patient (center) and father (right). Parental chromosomes were normal. Comparison of the heterochromatin in the pericentromeric region suggested that the deleted 7 of the patient was paternal in origin the low average range. In the present case, Greig syndrome is associated with a de novo deletion of chromosome 7, (p13p14), and is consistent with absence of hand or foot anomalies in either parent. Interestingly, polymorphisms of the pericentromeric, heterochromatin allowed the patients's chromosome 7 homologs to be distinguished. Cytogenetic analysis suggested that the deleted chromosome 7 was paternal in origin. It has been proposed that the majority of de novo structural chromosome rearrangements are paternal in origin, although paternal age is not necessarily increased (Olson and Magenis 1988). Greig syndrome was first suggested to map to 7p13 based on reports of apparently balanced translocations involving 7p13 segregating with the disorder in two different families. A de novo deletion in the same region of 7p in our patient, a sporadic, but classical case, supports this association. Recently, Rosenkranz et al. (1989) reported two unrelated infants with features of Greig syndrome (high forehead, hypertelorism, broad depressed nasal bridge, broad thumbs, duplicated great toes and syndactyly) and atypical, severe psychomotor retardation. One had an unbalanced reciprocal translocation between chromosomes 7 and 20 with loss of material between 7p11.2 and 7p13. The second had a de novo deletion with loss of material between 7p12.3 and 7p14.2. Based on the three cases with visible deletions of genetic material, the critical region in Greig syndrome appears to be band 7p13 (Fig. 5). This is the identical band involved in the familial translocation reports. Brueton et al. (1988) have reported genetic linkage of Greig syndrome to the D N A sequence coding for the

I

I

I

I

Fig. 5. On the right are shown the deleted segment in the present case compared with those of previously reported patients with 7p deletions and Greig syndrome or overlapping features. Critical region for Greig syndrome is 7p13 corresponding to the common breakpoint in the two translocation cases (denoted by arrow). Shown on the left are a selected number of loci known to map to 7p as assigned at the 10th International Workshop on Human Gene Mapping (Tsui et al. 1989). The map position of several loci has subsequently been refined (Wagner et al. 1990)

epidermal growth factor receptor ( E G F R ) , which maps to 7p13. Drabkin et al. (1989) demonstrated linkage to the T-cell receptor gamma ( T C R G ) locus, which is thought to map to 7p15. They did not find any rearrangement in a hybrid with the 3;7 translocation from a patient in the report by Tommerup and Nielsen (1983) using E G F R probes, suggesting it is not responsible for this syndrome. Xt mouse mutant heterozygotes have pre-axial polydactyly of the hind feet, residual postaxial tissue on the hind feet, an enlarged or duplicated pollux on the forefeet, an interfrontal bone in the skull, and occasional hydrocephaly (Winter and Huson 1988). This combination of anomalies is unusual but common to both mouse Xt mutants and Greig syndrome. The Xt locus has been mapped to mouse chromosome 13 in a region homologous to 7p in man (Searle et al. 1987). Evidence for homology between these two regions comes from localization of T C R G to 13A2-3 in the mouse (Kranz et al, 1985) and 7p15 in man (Murre et al. 1985). This data supports the hypothesis that the mouse mutant extra-toes (Xt) is the counterpart of Greig syndrome. Cytogenetic studies have not been routinely performed on patients with a diagnosis of Greig syndrome. A survey of the literature showed that 5 of 15 reported families with Greig syndrome have had chromosomes studies (4 banded, 1 unbanded). Two of the five families had abnormal cytogenetic studies (Tommerup and Nielsen 1983; Krtiger et al. 1989; Pelz et al. 1986) as discussed previously. Cytogenetic analyses have been per-

455 Table 1. Greig syndrome features in reports from the literature with deletion of the critical region 7p13

Clinical traits

Postaxial polydactyly, hands Broad/bifid thumbs Broad toes Preaxial polydactyly, feet Syndactyly Macrocephaly Prominent forehead Frontal bossing Hypertelorism Flat nasal bridge Developmental delay Paternal age (years) Maternal age (years)

Patient 1

2

3

4

5

6

7

(Bianchi et al. 1981)

(Bianchi et al. 1981)

(Muller et al. 1981)

(Crawfurd et al. 1979)

(Rosenkranz et al. 1989)

(Rosenkranz et al. 1989)

(Present case)

+

+

+ +

+ +

+ +

+ +

+ +

+ +

+

+

+ + + ? ?

+ + + ? ?

+ + 29 28

+ ? 30 16

+ + 30 23

formed in 4 of 6 reported sporadic cases and have been abnormal in 3 of the 4 (present case; Rosenkranz et al. 1989). Thus, Greig syndrome should be considered an autosomal dominant disorder whose etiology may sometimes be chromosomal. This case emphasizes the importance of performing chromosome analyses in Greig syndrome particularly those cases that are sporadic, atypical, or associated with psychomotor delay or retardation. We are aware of 12 reports in the literature involving an interstitial deletion on the short arm of chromosome 7, and 7 cases including the present one involve 7p13 (Table 1). All of the patients described (except one too young to be assessed) had some degree of developmental delay. Although none had been identified as having Greig syndrome, two had partial features of the disorder. Patient 1 reported by Bianchi et al. (1981) had bifid toes, broad thumbs, a prominent forehead with bossing, and a flattened nasal bridge. Mfiller et al. (1981) reported a patient with preaxial polydactyly of the feet, syndactyly, a prominent forehead, and flattened nasal bridge. The deleted segment in each case involved bands 7p13-p15 (Fig. 5). We suggest that Greig syndrome may be similar to retinoblastoma in that it is usually autosomal dominant and due to a submicroscopic mutation. Whether the mutation involves a single gene or several contiguous genes is unknown. In the familial cases, intelligence is usually normal, including the two reported families with an associated translocaton involving 7p13. However, sometimes, particularly in sporadic cases, the disorder may be caused by a microdeletion, and deletions of differing size and extent may explain some of the variability in phenotypic expression. Included in this variability of phenotypic expression, are varying degrees of intellectual deficits, which have been observed in retinoblastoma patients with microdeletions as well. Of the three known Greig syndrome patients who have a visible deletion (including the present case), all have some degree of devel-

+ 35 34

+ + + + + + + + + + + 31 30

opmental delay. As in retinoblastoma, both the familial and sporadic forms of Greig syndrome appear to map to the same locus (7p13). A number of loci on the short arm of chromosome 7 have been identified. A partial list is shown in Fig. 5. A homeobox-containing locus, Hox 1, is known to map to 7p14-p21 (Rabin et al. 1986). H o m e o b o x genes are involved in early embryogenesis and segmentation. Mutation or deletion involving such a homeobox gene could predispose to the digit (and possibly other) malformations that characterize Greig syndrome. However, the homologous homeobox locus maps to chromosome 6 in the mouse. Thus, this homeobox gene would not seem to be involved in the mouse mutant extra toes (which maps to mouse chromosome 13) nor in its human counterpart, Greig syndrome. Recent evidence in support of this is the report by Wagner et al. (1990), which did not find the Hox 1 locus to be deleted in either one of their Greig syndrome patients with a visible microdeletion. They also found the c D N A probe for interleukin 6 (interferon 13-2) to be present in normal gene dosage in their two patients and the c D N A probe for T C R G to be deleted in only one patient, thereby excluding a role for these two loci in Greig syndrome. Wagner et al. (1990) did find hemizygosity for the phosphoglycerate mutase muscular form (PGAM2) gene locus in both patients. Homozygosity for a P G A M 2 mutation is associated with a myopathy and low exercise intolerance. This clinical picture has not been reported in individuals with Greig syndrome making involvement of P G A M 2 seem less likely. Craniosynostosis is an occasional finding in Greig syndrome. Although a locus for craniosynostosis has been mapped to 7p21.2-21.3 (Motegi et al. 1985), it would appear to be too distal to be involved in Greig syndrome. A mutation in a gene influencing formation of digital rays (eventual fingers and toes) is a plausible etiology for the polysyndactyly observed in Greig syndrome. Inhibin beta A, which maps to 7p15-13 (Tsui

456 et al. 1989) a n d is k n o w n to inhibit f o l l i c l e - s t i m u l a t i n g h o r m o n e r e l e a s e f r o m t h e p i t u i t a r y g l a n d , is e x p r e s s e d in a v a r i e t y of tissues a n d m a y e x e r t effects as g r o w t h o r d i f f e r e n t i a t i o n f a c t o r s ( M e u n i e r et al. 1988). W h i l e e n d o c r i n e a b n o r m a l i t i e s h a v e n o t b e e n d o c u m e n t e d in G r e i g s y n d r o m e , i n h i b i n b e t a A c o u l d p l a y a role in the d i s o r d e r t h r o u g h an a b n o r m a l effect o n cell g r o w t h o r differentiation. T h e q u e s t i o n h a s b e e n r a i s e d as to w h e t h e r the Schinzel a c r o c a l l o s a l s y n d r o m e , w h i c h s h a r e s n u m e r o u s feat u r e s with G r e i g s y n d r o m e , m a y b e p a r t o f the v a r i a b i l i t y in p h e n o t y p i c e x p r e s s i o n t h a t occurs (Schinzel 1982). This d i s o r d e r differs f r o m G r e i g s y n d r o m e in t h a t t h e r e is s e v e r e m e n t a l r e t a r d a t i o n , agenesis of t h e c o r p u s call o s u m , a n d o n l y r a r e l y s y n d a c t y l y . C h r o m o s o m e studies h a v e b e e n p e r f o r m e d in 3 o f 11 r e p o r t e d cases a n d h a v e b e e n n o r m a l to d a t e . T h e m i l d d e g r e e o f d e v e l o p m e n t a l d e l a y a n d p r e s e n c e o f t h e c o r p u s c a l l o s u m in o u r case a r g u e a g a i n s t o u r p a t i e n t h a v i n g t h e a c r o c a l l o s a l synd r o m e . It w o u l d b e i n t e r e s t i n g to k n o w w h e t h e r t h e two p a t i e n t s with s e v e r e p s y c h o m o t o r d e l a y r e p o r t e d b y R o s e n k r a n z et al. (1989) h a v e a n y c e n t r a l n e r v o u s system (CNS) abnormalities. The acrocallosal syndrome m a y b e allelic to G r e i g s y n d r o m e o r r e p r e s e n t a physically c o n t i g u o u s locus. T h e l y m p h o b l a s t o i d cell line e s t a b l i s h e d on this p a tient will facilitate t h e i d e n t i f i c a t i o n o f D N A m a r k e r s a n d e x p r e s s e d s e q u e n c e s in t h e r e g i o n a n d , p e r h a p s , in clarifying the r e l a t i o n s h i p b e t w e e n G r e i g s y n d r o m e a n d the acrocallosal syndrome. R e l a t i v e l y few r e p o r t e d p a t i e n t s with G r e i g synd r o m e h a v e b e e n k a r y o t y p e d , a n d r e p o r t e d cases are l i k e l y to b e b i a s e d t o w a r d t h o s e with a c y t o g e n e t i c finding. H o w e v e r , since two o f five families a n d t h r e e o f f o u r i s o l a t e d cases h a v e h a d a t r a n s l o c a t i o n o r d e l e t i o n o f 7p13, a s s o c i a t e d c h r o m o s o m e a b n o r m a l i t i e s m a y n o t b e u n c o m m o n . W e feel c h r o m o s o m e analysis s h o u l d b e p e r f o r m e d in p a t i e n t s with k n o w n o r s u s p e c t e d G r e i g s y n d r o m e a n d in t h o s e with p a r t i a l f e a t u r e s of the diso r d e r b e c a u s e it c a n b e h e l p f u l in c o n f i r m i n g the diagnosis. I n families with G r e i g s y n d r o m e p a t i e n t s , w h e r e an a s s o c i a t e d 7p13 a b n o r m a l i t y is f o u n d , m o r e specific g e n e t i c c o u n s e l i n g r e g a r d i n g r e c u r r e n c e risks a n d p r e n a t a l d i a g n o s i s c o u l d t h e n b e given.

Acknowledgement. The authors would like to express their thanks to Ms. Sheri Rogers for her secretarial assistance in preparing this manuscript.

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deletions in two infants with differing congenital abnormalities. J Med Genet 16 : 453-460 Drabkin H, Sage M, Helms C, Green P, Gemmill R, Smith D, Erickson P, Hart I, Ferguson-Smith A, Ruddle F, Tommerup N (1989) Regional and physical mapping studies characterizing the Greig polysyndactyly 3;7 chromosome translocation, t(3;7) (p21.2p13). Genomics 4:518-529 Fryns JP, Coeck W, Berghe H van de (1977) The Greig polysyndactyly-craniofacial dysmorphism syndrome. Eur J Pediatr 126: 283-287 Gnamey D, Farriaux JP (1971) Syndrome dominant associant polysyndactolie, pouces en spatule, anomalies faciales et retard mental (une forme particuli6re de l' acroc6phalo-polysyndactylie de type Noack). J G6ndt Hum 19 : 299-316 Gollop TR, Fontes LR (1985) The Greig cephalopolysyndactyly syndrome: report of a family and review of the literature. Am J Med Genet 22 : 59-68 Hootnick D, Holmes LB (1972) Familial polysyndactyly and craniofacial anomalies. Clin Genet 3 : 128-134 Kranz DM, Saito H, Disteche CM, Pravtcheva D, Ruddle FH (1985) Chromosomal locations of the murine T-cell receptor alpha chain gene and the T-cell gamma chain gene. Science 227 : 941-945 Kr~ger G, G6tz J, Kvist U, Dunker H, Erfurth F, Pelz L, Zech L (1989) Greig syndrome in a large kindred due to a reciprocal chromosome translocation t(6;7)(q27;p13). Am J Med Genet 32 : 411-416 Meunier H, Rivier C, Evans RM, Vale W (1988) Gonadal and extragonadal expression of inhibin a, 13A and [3B subunits in various tissues predicts diverse functions. Proc Natl Acad Sci USA 85:247-251 Motegi T, Ohuchi M, Ohtaki C, Fujiwara K, Enomoto S, Hasegawa T, Kishi K, Hayakawa H (1985) A craniosynostosis in a boy with a del (7)(p15.3p21.3): assignment by deletion mapping of the critical segment for craniosynostosis to the midportion of 7p21. Hum Genet 71 : 160-162 Mtiller U, Staudt F, Hameister H (1981) A patient with intersitial deletion 7 (p13 p21) Ann G6nEt (Paris) 24 : 239-241 Murre C, Waldmann RA, Morton CC, Bongiovanni KF, Walsmann TA, Shows TB, Seidman JG (1985) Human gammachain genes are rearranged in leukemic T-cells and map to the short arm of chromosome 7. Nature 316: 549-552 Olson B, Magenis RE (1988) Preferential paternal origin of de novo structural chromosome rearrangements. In: Daniel A (ed) The cytogenetics of mammalian autosomal rearrangements. Liss, New York, pp 583-599 Pelz K, Krtiger G, GOtz J (1986) The Greig cephalopolysyndactyly syndrome. Helv Paediatr Acta 41 : 381-382 Rabin M, Ferguson-Smith A, Hart CP, Ruddle FH (1986) Cognate homeo-box loci mapped on homologous human and mouse chromosomes. Proc Natl Acad Sci USA 83:9104-9108 Rosenkranz W, Kroisel PM, Wagner K (1989) Deletion of EGFRgene in one of two patients with Greig cephalopolysyndactyly syndrome and microdeletion of chromosome 7p. Cytogenet Cell Genet 51 : 1069 Schinzel A (1982) Acrocallosal syndrome. Am J Med Genet 12: 201-203 Searle AG, Peters J, Lyon MF, Evans EP, Edwards JH, Bauckle VJ (1987) Chromosome maps of man and mouse, III. Genomics 1 : 3-18 Tommerup N, Nielsen F (1983) A familial reciprocal translocation t(3;7)(p21.2;p13) associated with the Greig polysyndactylycraniofacial anomalies syndrome. Am J Med Genet 16 : 313-321 Tsui L-C, Farrall M, Donis-Keller H (1989) Report of the committee on the genetic constitution of chromosomes 7 and 8. Cytogenet Cell Genet 51 : 166-201 Wagner K, Kroisel PM, Rosenkranz W (1990) Molecular and cytogenetic analysis in two patients with microdeletions of 7p and Greig syndrome: hemizygosity for PGAM2 and TCRG genes. Genomics 8 : 487-491 Winter RM, Huson SM (1988) Greig cephalopolysyndactyly syndrome: a possible mouse homologue (Xt-extra toes). Am J Med Genet 37 : 793-798

Greig syndrome associated with an interstitial deletion of 7p: confirmation of the localization of Greig syndrome to 7p13.

An 11-month-old infant with Greig cephalopolysyndactyly syndrome and mild developmental delay is described. High-resolution chromosomal analysis showe...
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