Dandy-Walker malformation with postaxial polydactyly: Further evidence for autosomal recessive inheritance

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  • Dandy-Walker Malformation With PostaxialPolydactyly: Further Evidence for AutosomalRecessive Inheritance

    D.P. Cavalcanti1,2* and M.A. Salomao21Depto. Genetica Medica, Faculdade de Ciencias Medicas, UNICAMP, Campinas, SP, Brazil2Ambulatorio de Genetica Perinatal, CAISM, UNICAMP, Campinas, SP, Brazil

    We describe an infant with Dandy-Walkermalformation and tetramelic postaxial poly-dactyly type 1A. Parental consanguinity re-inforces previous suggestions for autosomalrecessive inheritance. Am. J. Med. Genet.85:183184, 1999. 1999 Wiley-Liss, Inc.

    KEY WORDS: cerebellar vermis agenesis;postaxial polydactyly; auto-somal recessive inheritance;hydrocephalus

    INTRODUCTION

    The association of partial or complete absence of thecerebellar vermis, posterior fossa cyst communicatingwith the fourth ventricle, and facultative hydrocepha-lus has been described as the Dandy-Walker malfor-mation (DWM) [Hart et al., 1972]. It has been esti-mated to occur in about 4% of babies with hydroceph-alus [Kaiser et al., 1976] and can be found isolated or aspart of a Mendelian or chromosomal disorders. DWMmay also result from environmental factors [Murray etal., 1985]. The association of the DWM with postaxialpolydactyly has been described as a probable autoso-mal recessive syndrome (OMIM 220220). Here we de-scribe a newly affected child with parental consanguin-ity reinforcing autosomal recessive inheritance.

    CLINICAL REPORT

    The propositus is a male infant, product of the secondgestation of consanguineous parents (first-degree cous-ins). The first gestation of the couple resulted in a nor-mal female child. The propositus gestation was un-eventful up to early third trimester. An ultrasonogra-phy at 34 weeks evidenced polyhydramnios, posterior

    fossa cyst, cerebellar vermis agenesis, postaxial poly-dactyly of the four limbs, and discrete pelvic dilatationin the right kidney. Delivery was by Caesarean section.Apgar scores were 8 and 9 at 1 and 5 min. Birth weightwas 2600 g, length was 46 cm, and head circumferencewas 38 cm. Dysmorphisms noted after birth were mac-rocephaly with dolicocephalus, broad and depressednasal bridge, low-set ears, microretrognathia, and tet-ramelic postaxial polydactyly (Fig. 1) with a 6th well-formed digit on both hands and feet [polydactyly type1Asee Temtamy and McKusick, 1978]. Cerebral ul-trasonography in the first days showed large posteriorfossa cyst, cerebellar hypoplasia, and normal supraten-torial ventricular system. Radiographs examinationsdemonstrated a midline occipital defect in the skullinferior to the lambdoid suture and postaxial polydac-tyly of hands and feet with enlargement of all fifthmetacarpal and metatarsal bones. The fifth metacar-pals were also bifid. Neonatal abdominal ultrasonogra-phy confirmed prenatal diagnosis of discrete pelvic di-latation on the right. However, a second examinationat the age of 3 months failed to show any abdominalabnormality. CT of the brain at 2 months showed ac-centuated cerebellar hypoplasia with vermis hypopla-sia and separated hemispheres, posterior fossa cystcommunicating with fourth ventricle, and enlargementof the third ventricle compatible with the DWM (Fig.2). Karyotype was normal (46,XY).

    DISCUSSION

    The DWM is a well-known CNS abnormality, whichcan be associated with a variety of well-defined condi-tions. Murray et al. [1985] in a table summarizes theseconditions where several Mendelian, chromosomal,and environmental disorders are reported beside mul-tifactorial and sporadic conditions. The DWM withpolydactyly has been described isolated and associatedwith other malformations. In a clinicopathologicalstudy of 28 cases, Hart et al. [1972] described 3 cases ofthe DWM associated with polydactyly. However, theseauthors did not relate details about the polydactyly as-pect. Egger et al. [1982] related two affected sibs in thesame family, a girl and her brother, presenting the

    Correspondence to: Denise Pontes Cavalcanti, Depto. GeneticaMedica, FCM, UNICAMP, C.P. 6111 Campinas, SP, Brazil13081970. E-mail: dpc@turing.unicamp.br

    Received 22 February 1999; Accepted 2 March 1999

    American Journal of Medical Genetics 85:183184 (1999)

    1999 Wiley-Liss, Inc.

  • DWM plus polydactyly. The girl had tetramelic post-axial polydactyly and DWM with absence of cerebellumand episodes of apnea alternated with tachypnea; herbrother presented the same clinical features plusfleshy nodules on the tongue and numerous wormianbones. Because of the presence of episodes of irregularrespiration as well as fleshy nodules in the second sib,Egger et al. [1982] pointed to two diagnostic possibili-ties: Joubert-Boltshauser syndrome with polydactylyand tongue nodules or Mohr syndrome. The Mohr syn-drome has a particular pattern of polydactyly. It ischaracterized by midline partial cleft of lip, tonguewith cleft and nodules, and bilateral postaxial polydac-tyly with polysyndactyly of halluces [Gorlin et al.,1990]. Some cases of Mohr syndrome, however, can alsopresent CNS anomalies and sometimes DWM [Gustav-son et al., 1971; Haumont and Pele, 1983]. Pierquin etal. [1989] described two sibs presenting the DWM andpostaxial polydactyly with the extra digit well-formedand suggest that these cases and the two related byEgger et al. [1982] can represent a new autosomal re-cessive syndrome (OMIM 220220). The case here re-lated presenting DWM and tetramelic postaxial poly-dactyly with the extra digit well-formed resembles thecases previously described by Egger et al. [1982] andPierquin et al. [1989]. The parental consanguinityfound in the present case strongly suggests the auto-somal recessive inheritance of the defined syndrome.

    REFERENCESEgger J, Bellman MH, Ross EM, Baraitser M. 1982. Joubert-Boltshauser

    syndrome with polydactyly in siblings. J Neurol Neurosurg Psychiat45:737739.

    Gorlin RJ, Cohen MM, Levin AS. 1990. Syndromes of the head and neck.3rd ed. New York: Oxford University Press.

    Gustavson KH, Kreuger A, Petersson PO. 1971. Syndrome characterizedby lingual malformation, polydactyly, tachypnea, and psychomotor re-tardation (Mohr syndrome). Clin Genet 2:261266.

    Hart MN, Malamud N, Ellis W. 1972. The Dandy-Walker syndrome. Neu-rology 22:771780.

    Haumont D, Pele S. 1983. The Mohr syndrome: are there two variants?Clin Genet 24:4146.

    Kaiser G, Schut L, James HE, Bruce DA. 1976. Problems of diagnosis andtreatment in the Dandy-Walker syndrome. Mod Probl Paediatr 2:123124.

    Murray JC, Johnson JA, Bird TD. 1985. Dandy-Walker malformation: etio-logic heterogeneity and empiric recurrence risks. Clin Genet 28:272283.

    Pierquin G, Deroover J, Levi S, Masson T, Hayez-Delatte F, VanRegemorter N. 1989. Dandy-Walker malformation with postaxial poly-dactyly: a new syndrome? Am J Med Genet 33:483484.

    Temtamy SA, McKusick VA. 1978. The genetics of hand malformations.New York: The National FoundationMarch of Dimes, BDOAS, VolXIV, Number 3.

    Fig. 1. Propositus at 3 days of age. Note dolicocephalus and postaxialpolydactyly of the four limbs.

    Fig. 2. Computerized tomography performed at 3 months of age. Notevermis hypoplasia, separated hemispheres, and posterior fossa cyst.

    184 Cavalcanti and Salomao

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