A morpho-etiological description of congenital limb anomalies

CONGENITAL LIMB ANOMALIESTable 1. Fetal causes of limb anomalies.Etiology/SyndromeNumberof casesLimb anomaliesPresentationAssociated anomaliesChromosomal aberrations 9Trisomy 13 5 Postaxial polydactyly Holoprosencephaly, microcephaly,cleft lip/palateDuplication 13 (13q+) 1 Postaxial polydactyly Congenital heart, blepharophimosis,long philtrumTrisomy 18 1 Preaxial polydactyly Micognathia, clenched hands,protruded occiput, malformed ears,overlapping fingersCATCH 22 (22q-) 1 Postaxial polydactyly (F) Congenital heart, abnormal face,thymus hypoplasia, cleft palate,hypocalcaemiaTrisomy 21 1 Syndactyly 4th, 5th fingers Upward slanting palpebral fissures,low-set ears, depressed nasal bridge,hypotonia, mental retardationSingle gene disorders 30Isolated polydactyly (AD) 12 Polydactyly (F and/or T)Synpolydactyly (AD) 5 Synpolydactyly (F or T)Meckel-Gruber synd. (AR) 3 Polydactyly (F and/or T) Anencephaly, polycystic kidney, cleftpalateApert syndorome (AD) 2 Acrosyndactyly (F) Craniosynostosis, flat face, downslanting palpebral fissuresRadial ray defect (AD or AR) 2 Absent thumb, radial hypoplasia Ventricular septal defectFraser syndrome (AD) 1 Acrosyndactyly (F and T) Eyes covered by forehead skin, no eyelids, anal atresiaBardet-Biedl syndrome (AR) 1 Postaxial polydactyly (F and T) Obesity, retinal pigmentation,ventricular septal defectSyndactyly (AD) 2 Syndactyly (F or T)Split hand/foot syndrome (AD) 1 Absent middle finger, absent secondtoe, syndactyly 3rd and 4th toesTriphalangeal thumb polydactylysyndrome (AD)Total cases 39F=fingers, T=toes1 Triphalangeal thumb, preaxialpoldactylyAnn Saudi Med 25(3) May-June 2005 www.kfshrc.edu.sa/annals 221

CONGENITAL LIMB ANOMALIESFigure 1. Limb anomalies due to fetal causes (chromosomalaberrations).a) Bilateral cutaneous syndactyly of the little and ring fingers(arrow) and right little finger clinodactyly (arrow) in a short broadhand of a Down syndrome child (trisomy 21).b) Left preaxial polydactyly (arrow) in a newborn male withEdward’s syndrome (trisomy 18). Note the malformed low-set andposteriorly rotated ears, the micrognathia, the clenched hand,and the overlapping fingers.c) Left postaxial polydactyly (arrow) in a newborn male withpartial trisomy 13 (13q+). Other dysmorphic features includebulging forehead, blepharophimosis, deep-set eyes, depressednasal bridge, long philtrum, thin upper lip, and pectus excavatum.Figure 2. Showing limb anomalies due to fetal causes (singlegene disorders).a) Triphalangeal and distally displaced left thumb (short arrow)with thenar muscles hypoplasia, and preaxial polydactyly (longarrow) in an infant with the autosomal dominant triphalangealthumb polydactyly syndrome.b) Isolated preaxial polydactyly (arrow).c) Bilateral preaxial autosomal dominant synpolydactyly. Thesecond toe is duplicated and fused (arrows).224Ann Saudi Med 25(3) May-June 2005 www.kfshrc.edu.sa/annals

CONGENITAL LIMB ANOMALIEScases with Poland sequence and classified the handanomalies into seven types according to severity ofthe deformity. Sirenomelia (vitelline artery steal) isanother example of vascular disruption leading toabnormal caudal development. 24 Five cases (7.1%) inthe present study suffered from limb anomalies dueto vascular disruption in the embryonic blood vessels.Vascular anastomoses and discordant placental bloodflow in twins with a common placenta predisposethem to vascular disruptions. In approximately 1%of monozygotic twins, intrauterine death of one twinmay result in release of thromboplastin or emboli tothe surviving co-twin leading to ischemia in localizedareas. 17 One patient in the present study hadgangrene and muscle atrophy of both lower limbs.He was one of a triplet. Other causes of vasculardisruption include placental infarction, maternal hypotension,vasoactive drugs, agents like cocaine andcertain medications. 17 e prenatal diagnostic technique,chorionic villus sampling (CVS), has also beenassociated with limb reduction defect, with anoxia ofdistal fetal structures as a postulated etiology. 39Infants of diabetic mothers have 6% risk of developingcongenital malformations. e risk maybe over 20% if there is poor control during thefirst trimester. e malformations involve the heart(transposition of great vessels), anencephaly, spinabifida, holoprosencephaly, cleft lip and/or palate, renalanomalies and caudal regression sequence. 17 Onecase with caudal regression in the present study wasan infant of an uncontrolled diabetic mother.Twenty cases (28.6%) in the present study hadlimb anomalies as one of the manifestations of sporadicsyndromes (syndromes with unknown etiology).Acheiria (rudimentary hand and fingers) andaphalangia (transverse limb anomalies) are probablycaused by death of the mesenchymal cells in the limbbud region. 40 Ruiter et al 41 have described absent lefthand (a terminal transverse reduction defect) in aboy with mosaic trisomy 22. ey observed that thistype of limb anomalies has never been reported inassociation with this chromosomal aberration. isfinding points out the importance of genetics in thework-up in sporadic cases of limb anomalies.Watson 42 stressed that management of congenitallimb anomalies has to include classificationand etiology, incidence, diagnosis before birth,and counseling of parents. In a similar study doneby Holder-Espinasse et al 43 on 107 cases of limbanomalies, the diagnosis was made in 78%, includingisolated, syndromic, or chromosomal anomalieswith the conclusion that prenatal multidisciplinaryFigure 3 (a,b). Limb anomalies due to fetal causes (single genedisorders).A newborn boy with bilateral postaxial synpolydactyly of the ringfinger (short arrows) and bilateral preaxial synpolydactyly of thebig toe (long arrow).Figure 4 (a,b). Limb anomalies due to environmental causes.Limb anomalies due to amniotic band disruption: a) constrictionrings (arrow), syndactyly, and ectrodactyly or terminal phalangesamputations; b) Transverse limb defect, i.e. amputation of both feet.Ann Saudi Med 25(3) May-June 2005 www.kfshrc.edu.sa/annals 225

CONGENITAL LIMB ANOMALIESFigure 5. Limb anomalies due to environmental causes.a) A newborn with sirenomelia (due to vascular disruption)where both lower limbs and feet are fused, absent externalgenitalia and imperforate anus.b) A newborn with general vascular disruption presented withbilateral limb amputation (transverse reduction defect), absentright thumb and index finger, right radial hypoplasia (radial raydefect), absent external genitalia, and blue colored skin.c) Bilateral gangrene of the leg and foot due to abnormalcirculation in one of a triplet.Figure 6. Limb anomalies due to sporadic causes.a) Acheiria (transverse limb defect) in a newborn boy where theleft palm is absent and the fingers are rudimentary and presentedby digital buds (arrow), b) Tetraperomelia in a newborn boy(amputation in both upper and lower limbs), c) Bifid thumb.226Ann Saudi Med 25(3) May-June 2005 www.kfshrc.edu.sa/annals

CONGENITAL LIMB ANOMALIESassessment is fundamental to assist with counseling, asis the postnatal follow-up of the infant. e diagnosis,if made, will obviously influence the information thatwill be given to the parents and the management ofthe malformation, and guide recurrence risks.In conclusion, the etiological study, including thegenetic work-up, of morphologically classified caseswith congenital limb anomalies is helpful in theprevention of many disorders causing limb defects.Prevention can be achieved via proper genetic counseling,which includes information on the etiologyof the disorder (genetic or environmental), prenataldetection of limb anomalies and risk estimation forlater siblings.References1. O’Quinn JR, Hennekam RC, Jorde LB, BamshadM. Syndromic ectrodactyly with severe limb, ectodermal,urogenital, and palatal defects maps tochromosome 19. Am J Hum Genet. 1998;62(1):130-5.2. Giele H, Giele C, Bower C, Allison M. 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