Deletion 2Q24

Deletion 2q24

Authors: Doctor Saskia M. Maas1 Scientific editor: Professor Raoul CM Hennekam

Creation date: June 2001 Update: March 2004

1Department of Clinical Genetics, Academic Medical Centre, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam. The Netherlands. mailto:S.M. [email protected]

Abstract Key words Disease name and synonyms Excluded diseases Diagnosis criteria/definition Differential diagnosis Prevalence Clinical description Management including treatment Etiology Diagnostic methods Genetic counselling Antenatal diagnosis Unresolved questions References

Abstract Deletion of 2q24, i.e. the loss of a small but specific region of the long arm of chromosome 2 forms a clinically recognizable syndrome. Twenty-three cases are known from the literature. Several symptoms are commonly seen in patients with chromosome aberrations, such as low birth weight, growth retardation, mental retardation, and low and malformed ears. However, the eye anomalies (coloboma, cataract and microphthalmia), anomalies of hands and feet (flexion deformities) and the congenital heart defects are more specific features, and are especially important in recognizing the clinical phenotype.

Key words chromosome 2q23q24, interstitial deletion, camptodactyly, eye anomalies, cardiac defects

Disease name and synonyms and feet and/or heart defects seem to be more Deletion of chromosome band 2q24 specific for this deletion. Monosomy 2q24 Differential diagnosis Excluded diseases If the cytogenetic anomaly is detected, no All the other chromosome anomalies associated differential diagnosis is needed. If no with low birth weight, growth retardation, mental microdeletion at 2q24 can be found the clinical retardation and facial dysmorphism. features may point to a vast array of other chromosome anomalies of monogenic entities. Diagnosis criteria/definition The diagnosis is made when chromosome Prevalence analysis shows a deletion of a specific part To our knowledge there are twenty-three (band q24) of the long arm of chromosome 2. reported cases (in detail) with a deletion Because many of the clinical symptoms are non- involving chromosome band 2q24. There are no specific the clinical symptoms are not part of the exact data about the prevalence of this diagnostic criteria. However, the combination of chromosome aberration. low birth weight, growth retardation, mental retardation, facial dysmorphism together with eye anomalies, flexion deformities of the hand

Maas SM. Deletion 2q24. Orphanet encyclopedia. March 2004 http://www.orpha.net/data/patho/GB/uk-2q24.pdf 1

Clinical description Flexion deformities of the fingers have been The most frequent abnormalities are growth reported in most cases. A common deleted retardation, poor neurological development segment in all these cases is q24.3, except in (mental retardation, hypotonia, seizures), one case, who has joint contractures of several microcephaly, malformed and low-set ears with fingers, who had a deletion of the 2q21q23.2 sometimes large and fleshy ear lobes, eye segment. anomalies (ptosis, coloboma, cataract), Apparently both the 2q24.3 region and the depressed nasal bridge with a small upturned 2q31.1 region are responsible for limb defects. nasal tip, micrognathia, flexion deformities of the The present data suggest that deletions of the fingers, sandal gap, and congenital heart 2q24.3 region are more often associated with defects. The association of growth retardation finger flexion deformities. Except for a sandal and poor neurological development together with gap between the first and second toe no other multiple minor facial anomalies is a common feet anomalies were described in patients with denominator to many deletion syndromes. The deletions in this region, providing that they did eye anomalies (one or more in ten of the not have in addition a deletion in the 2q31.1 patients), digital flexion deformities (fourteen region. Data suggest furthermore that the more patients) and congenital heart defects (eight distal the deletion is located, the more severe patients) are more specific features. the reported hand and feet anomalies are. Split feet may represent the extreme end of the Neurologic symptoms spectrum of digital anomalies associated with Microcephaly, abnormal head shape (sagittal deletions in this region. synostosis, craniosynostosis, cranial sutural irregularities and scaphocephaly), occipital Heart anomalies meningomyelocele and internal hydrocephalus, Different congenital heart defects have been occipital encephalocele and ventricular present in 8 patients. Ventricular septal defects enlargement and seizures were prominent were described in 4 patients, atrial septal defect findings in most of the patients. This made in three patients, aortic coarctation in two authors to suggest that some of the many genes, patients, a truncus arteriosus was described in 2 which have significant impact on brain patients and a patent ductus arteriosus in 3 development, and function may be located in the patients. Segment 2q24.2 is deleted in 4 of the 8 q22.3 through q31 region of chromosome 2. patients but is also deleted in one case in which ECG and auscultation were normal. Eye involvement Eye anomalies are reported in half of the Management including treatment patients. Different eye anomalies are described. Management of the growth retardation and Ptosis is reported in 7 patients. Microphthalmia mental retardation should be taken care of is only reported in 2 patients. Cataract is similar to the care for any other child with these mentioned in 3 cases. These three patients have features. The other clinical features caused by a common deleted segment in q23.3q24.2. the deletion, like the camptodactyly or cardiac However, two other patients in whom defects, should be treated in a similar way. ophthalmologic examination did not show cataract also have this segment deleted, and in Etiology another case with again deletion of this segment This syndrome is the result of a deletion of an cloudy corneas were found, which attributed to interstitial part of the long arm of chromosome 2. ocular immaturity. In another patient with a In almost all the cases the deletion will arise deletion of the 2q23.3q24.3 segment no spontaneously, probably due to a disturbance of ophthalmic examination was performed. the first meiotic division in either parent. Therefore it is unlikely that band q23.3q24.2 is a An increasing number of genes are mapped to critical region for cataract. Colobomas were the region 2q24 (OMIM). No single gene seems reported in 5 patients. to be able to explain all symptoms, making the deletion 2q24 probably a continuous genes Acral defects syndrome. Genes in this region involved in the Bilateral digital anomalies are often found, and phenotype of patients with a 2q24 deletion may have included camptodactyly, also of the be several neuronal voltage dependant sodium thumbs, clinodactyly of the fifth fingers, short feet channel genes (SCN1A, 2A1, 2A2 and 3a). with broad halluces, absent second digits, Mutations in the SCN1A gene are for example hypoplastic third, fourth and fifth digits, associated with generalized epilepsy with febrile syndactyly of the 2nd or 3rd to 5th toe, and a seizures and are described as a major cause of clefting between the halluces and the other severe myoclonic epilepsy of infancy. No digits, best described as a split foot.

Maas SM. Deletion 2q24. Orphanet encyclopedia. March 2004 http://www.orpha.net/data/patho/GB/uk-2q24.pdf 2 candidate genes for the congenital defects of recognizable microdeletion syndrome? Clin brain, eyes and limbs are known. Dysmorhhol 2000;9:47-53. McConnell TS, Kornfeld M, McClellan G, Aase Diagnostic methods J. Partial deletion of chromosome 2 mimicking a One should look for a deletion of chromosome phenotype of trisomy 18: Case report with 2q24 if the clinical symptoms are suggestive. A autopsy. Hum Pathol 1980;11:202-205. deletion of chromosome 2q24 is usually visible McMilin KD, Reiss JA, Brown MG, Black MH, on a standard karyotype if suspicion for this Buckmaster DA, Durum CT, Gunter KA, Lawce anomaly is expressed due to the clinical HJ, Berry TL, Lamb OA, Olson CL, Weeks FF, features. FISH studies may be indicated. Yoshitomi MJ, Jacky PB, Olson SB, Magenis RE. Clinical outcomes of four patients with Genetic counselling microdeletion in the long arm of chromosome 2. If a deletion of chromosome 2q24 is found in a Am J Med Genet 1998;78:36-43. child chormosome analysis should be performed Moller M, García-Cruz D, Rivera H, Sánchez- in the parents and other family members should Corona J, Cantú JM. Pure monosomy and be counselled according to the cytogenetic trisomy 2q24.2-q3105 due to an inv ins results. (7;2)(q21.2;q3105q24.2) segregating in four generations. Hum Genet 1984;68:77-86. Antenatal diagnosis Mowat DR, Croaker GDH, Cass DT, Kerr BA, If the chromosome anomaly is caused by a Chaitow J, Adès, Chia NL, Wilson MJ. translocation present in one of the parents, Hirschsprung disease, microcephaly, mental antenatal diagnosis may be offered because of a retardation, and characteristic facial features: recurrence risk. If parental karyotypes are both delineation of a new syndrome and identification normal the recurrence risk is very low, and of a locus at chromosome 2q22-q23. J Med depending on the presence of absence of germ Genet 1998;35:617-623. line mosaicism in one of the parents. Antenatal Nixon J, Oldridge M, Wilkie AO, Smith K. diagnosis in a next pregnancy may still be Intertsitial deletion of 2q associated with offered, for psychosocial reasons. craniosynostosis, ocular coloboma and limb abnormalities: Cytogenetic and molecular Unresolved questions investigation. Am J Med Genet 1997;70:324- Most of the gene(s) that are causative for the 327. different parts of this microdeletion syndrome are OMIM: http://www4.ncbi.nlm.nih.gov/htbin- still unknown. post/Omim/getmap?chromosome=2q24Palmer CG, Heerema N, Bull M. Deletion in References chromosome 2 and fragile sites. Am J Med Bernar J, Sparker RS, Allensworth S. Interstitial Genet 1990;36:214-218. deletion 2q24.3: Case report with high resolution Ramer JC, Ladda RL, Frankel CA, Beckford A. banding. J Med Genet 1985;22:226-228. A review of phenotype-karyotype correlations in Boles RG, Pober BR, Gibson LH, Willis CR, individuals with interstitial deletions of the long McGrath J, Roberts DJ, Yang-Feng TL (1995). arm of chromosome 2. Am J Med Genet Deletion of chromosome 2q24-q31 causes 1989;32:359-363. characteristic digital anomalies: Case report and Shabtai F, Klar D, Halbrecht J. Partial review. Am J Med Genet 1995;55:55-160. monosomy of chromsome 2. Delineable Chinen Y, Tohma T, Izumikawa Y, Iha T, Goya syndrome of deletion 2 (q23-q31). Ann Genet Y, Naritomi K. Small interstitial deletion of the 1982;25:156-158. long arm of chromosome 2 (2q24.3): Further Sharma J, Friedman D, Schiller M, Flynn P, delineation of 2q medial monosomy syndrome. Alonso ML. Aortic stenosis in hypoplastic right Jpn J Hum Genet 1996;41:323-328. heart syndrome, associated with interstitial Fryns JP, van Bosstraeten B, Malbrain H, van deletion of chromosome 2. Int J Card den Berghe H. Interstitial deletion of the long 1997;62:199-202. arm of chromosome 2 in a polymalformed Slavotinek A, Schwarz C, Getty JF, Stecko O, newborn karyotype: 46,XX, del(2)(q21;q24). Goodman F, and Kingston H. Two cases with Hum Genet 1977;39:233-238. interstitial deletions of chromosome 2 and sex Lurie IW, Supovitz KR, Rosenblum-Vos LS, reversal in one. Am J Med Genet 1999;86:75-81. Wulfsberg EA. Phenotypic variability of del(2) Takahashi Y, Narahara K, Kikawa K, Wakita Y, (q22-q23): report of a case with a review of the Kimura S, Murakami M, Kazai R, Kimoto H. literature. Genet Couns 1994;5:11-14. Interstitial deletion of the long arm of Maas SM, Hoovers JM, van Seggelen ME, chromosome 2: A case report and review of the Menzel DM, Hennekam RCM. Interstitial deletion literature. Jinrui Idengaku Zasshi 1985;30:297- of the long arm of chromosome 2: a clinically 305.

Maas SM. Deletion 2q24. Orphanet encyclopedia. March 2004 http://www.orpha.net/data/patho/GB/uk-2q24.pdf 3

Valero-Huezo S, Fragoso R, Rievra H, Moller M, Woods CG, Koehn DC, McFadden DE, Evans Cantu JM. Del(2)(q2300q24.1) de novo. Bol Med JA , van Allen MI. A case report of a child with Hosp Infant Mex 1986;43:375-377. an interstitial deletion of chromsome 2 Wamsler C, Müller B, Freyberger G, Schmid M. (q22;q24.2) and the VATER association Interstitial deletion del(2)(q24q31) with a phenotype. Abstr. D.W. Proc Greenwood Genet phenotype similar to del(2)(q31q33). Am J Med Ctr 1993;12:119-120. Genet 1991:39:204-206.

Maas SM. Deletion 2q24. Orphanet encyclopedia. March 2004 http://www.orpha.net/data/patho/GB/uk-2q24.pdf 4