Adams-Oliver syndrome: Autosomal recessive inheritance and new phenotypic-anthropometric findings

  • Published on

  • View

  • Download

Embed Size (px)


  • Brief Clinical Report

    Adams-Oliver Syndrome: Autosomal RecessiveInheritance and NewPhenotypic-Anthropometric Findings

    Gil Klinger1,2 and Paul Merlob1,2*1Department of Neonatology, Rabin Medical Center and Schneider Childrens Medical Center of Israel,Petah Tiqva, Israel

    2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    We describe a new family with Adams-Oliver syndrome. One sib had scalp aplasiacutis congenita (SACC) and cutis marmo-rata and a second sib had SACC, cutis mar-morata, and terminal lower limb defects. Inboth the findings were associated with oli-gohydramnios. The pedigree suggests auto-somal recessive inheritance. New pheno-typic-anthropometric findings in one infantwere upper limb micromelia and brachypo-dia. Am. J. Med. Genet. 79:197199, 1998. 1998 Wiley-Liss, Inc.

    KEY WORDS: Adams-Oliver syndrome;scalp aplasia cutis congenita;autosomal recessive; oligohy-dramnios; brachypodia; mi-cromelia


    Adams-Oliver syndrome (McKusick 10030) is char-acterized by the presence of scalp aplasia cutis conge-nita (SACC) with distal limb anomalies [Adams andOliver, 1945]. Cutis marmorata and dilated scalp veinsare additional frequent manifestations of the condition[Kuster et al., 1988; Whitly and Gorlin, 1991; Zapata etal., 1995]. We present a family with Adams-Oliver syn-drome and describe some new phenotypic-anthro-pometric findings.

    CLINICAL REPORTThe proposita (III-4; Fig. 1) was the fourth child of a

    25-year-old mother, gravida 3 para 4, and a 34-year-old

    father. Both parents are healthy, nonconsanguineous,and of Iranian origin. There are no known illnesses intheir families. The first pregnancy was complicated byoligohydramnios and resulted in the birth of a boy (III-1; Fig. 1) with SACC and cutis marmorata. The secondpregnancy resulted in the birth of healthy twins. In thethird pregnancy (the proposita) there was oligohy-dramnios diagnosed by ultrasound, which also demon-strated dolicocephaly. There was no history of use ofmedications, X-ray exposure, alcohol intake, drug use,or smoking during this pregnancy.

    The preterm infant was born at 36 weeks of gestationand delivered by cesarean section because of previouscesarean section and breech presentation. At birth,there was almost complete absence of amniotic fluid.Apgar scores were 9 and 10 at 1 and 5 min, respec-tively. Birth weight was 2,370 g, length 47.5 cm, andhead circumference 32.5 cm, all appropriate for gesta-tional age. The head was dolicocephalic with high fore-head, large fontanels, large third fontanel, and opensaggital suture. There was a hairless area 10 2 cm inthe right paramedian frontoparietal region (Fig. 2).The underlying skin was thin and yellowish, but nobone defects were found by palpation. Dilated veinscovered the scalp defect. Other findings were sparsefrontal hair; incomplete whorl but normal clockwise ro-tation; normal eyes, ears, nose; high arched palate; leftdouble nipple; small umbilical hernia; and pilonidaldimple with hair. The upper limbs were normal, butthere was bilateral brachydactyly of toes II to IV (Fig.3), mild cutaneous syndactyly of toes II and III, smalltoenails, and mild bilateral pes valgus. Generalized cu-tis marmorata was noted (Fig. 4). Anthropometric mea-surements documented a small biparietal diameter(below 2 SD) [Merlob et al., 1984], with a large an-teroposterior diameter (above +2 SD); both measure-ments were the result of the dolicocephalic shape of thehead. Total arm length (17 cm) was consistent withupper limb micromelia (below 2 SD), and total leglength (17 cm) was normal, but foot length (6.3 cm)showed brachypodia (below 2 SD).

    *Correspondence to: Prof. P. Merlob, Head, Department of Neo-natology, Rabin Medical Center, Beilinson Campus, Petah Tiqva49100, Israel.

    Received 3 December 1997; Accepted 15 June 1998

    American Journal of Medical Genetics 79:197199 (1998)

    1998 Wiley-Liss, Inc.

  • Results of routine laboratory investigations (com-plete blood count, blood chemistry, and urinalysis)were normal. Skeletal survey did not show any asym-metry and was normal except for the skull film, whichwas consistent with dolicocephaly. Brain ultrasoundwas normal. Karyotype was normal (46,XX).

    Follow-up examination of the proposita (III-4; Fig. 1)at age 6 confirmed presence of SACC, brachypodia, bi-lateral brachydactyly of the second to fourth toes, anddolicocephaly. Follow-up examination of the olderbrother (III-1; Fig. 1) at age 8 showed SACC, but noother abnormalities. The cutis marmorata, noted atbirth, had resolved by age 2 years in both sibs (III-1and III-4; Fig. 1). Since the propositas first examina-tion two additional children were born. All children areat the normal neurodevelopmental stage for age and allrelatives have normal intelligence. Physical examina-tion of both parents, including thorough examination ofthe skull, was normal with no evidence of SACC or limbdefects.


    Adams-Oliver syndrome is diagnosed when SACCand distal limb anomalies are present concomitantly.The scalp defect, which is situated at the vertex, maybe subtle or in rare cases extensive, with a large defectin the cranium and the underlying vessels. Other de-fects that have been rarely associated with Adams-Oliver syndrome are: congenital heart disease, super-numerary nipples, cryptorchidism, microphthalmia,aplasia cutis congenita at the knee, woolly hair, cleft

    lip, and duplicated collecting system [Whitly and Gor-lin, 1991].

    In almost all reported patients with Adams-Oliversyndrome the inheritance was autosomal dominant[Kuster et al, 1988; Whitly and Gorlin, 1991]. Autoso-mal dominant inheritance with incomplete penetrancewas reported in at least six families [Adams and Oliver,1945; Scribanu and Temtamy, 1975; Burton et al.,1976; McMurray et al., 1977; Bonafede and Beighton,1979; Hidalgo et al., 1983). Only two reports suggestedautosomal recessive inheritance [Kahn and Olmedo,1950; Koifman et al., 1987]: Both these families werecharacterized by multiple affected offspring of unaf-fected parents. In the report by Koifman et al. [1987]parental consanguinity provided additional support forautosomal recessive inheritance.

    The pathogenesis of aplasia cutis congenita is stillunclear today. In their review, Blunt et al. [1992] sug-gest that vascular disruption is a common mechanismcausing this phenomenon. An alternate mechanismmay be compression caused by oligohydramnios. In thefamily described, mild to moderate oligohydramnios

    Fig. 1. Pedigree of family with Adams-Oliver syndrome. Arrow marksproposita, shading marks affected person.

    Fig. 2. Scalp, showing cutis aplasia congenita.

    Fig. 3. Brachydactyly of toes.

    Fig. 4. Generalized cutis marmorata.

    198 Klinger and Merlob

  • was present in one and severe oligohydramnios waspresent in a second sib. Oligohydramnios seems an un-likely cause of SACC in one sib because it was not ofsufficient severity. In both sibs SACC was not an iso-lated finding, and additional manifestations of Adams-Oliver syndrome were present, thus providing evidenceagainst oligohydramnios being the primary cause.

    We present a third family with probable autosomalrecessive inheritance in which two sibs had signs ofAdams-Oliver syndrome, but the parents did not. Onechild had scalp cutis aplasia and cutis marmorata andthe other had the same anomalies and terminal limbdefects.

    We cannot rule out the possibility of autosomal dom-inant inheritance with incomplete penetrance in thisfamily. However, the lack of even subtle evidence ofthis syndrome in the parents or other relatives arguesagainst this form of inheritance.

    Anthropometric measurements demonstrated upperlimb micromelia and brachypodia. The lower limblength was within the normal range. Small biparietaldiameter and large anteroposterior diameter consis-tent with dolicocephaly were also found. These anthro-pometric findings have not been reported previously.

    Follow-up examination of the family reaffirmed thatnormal intelligence is to be expected in this syndrome.Cutis marmorata observed at birth resolved within thefirst two years of life.

    Another observation not previously reported in asso-ciation with Adams-Oliver syndrome is oligohydram-nios with normal renal function after birth.


    Adams FH, Oliver CI (1945): Hereditary deformities in man due to ar-rested development. J Hered 36:37.

    Blunt K, Quan V, Carr D, Paes BA (1992): Aplasia cutis congenita: Aclinical review and associated defects. Neonatal Netw 11:1727.

    Bonafede RP, Beighton P (1979): Autosomal dominant inheritance of scalpdefects with ectrodactyly. Am J Med Genet 3:3541.

    Burton BK, Hauser L, Nadler HL (1976): Congenital scalp defects withdistal limb anomalies: Report of a family. J Med Genet 14:466468.

    Hidalgo JE, Greer DM, Johnston DW (1983): Congenital scalp defect withdistal limb anomalies: Brachydactyly and hypoplastic toes. Plast Re-constr Surg 72:708711.

    Kahn EA, Olmedo L (1950): Congenital defect of the scalp with a note onthe closure of scalp defects in general. Plast Reconstr Surg 6:435440.

    Koifman CP, Wajntal A, Huyke BJ, Castro RM (1987): Congenital skulldefects with distal limb anomalies (Adams-Oliver syndrome McKusick10030): Further suggestion of autosomal recessive inheritance. Am JMed Genet 29:26368.

    Kuster W, Lenz W, Kaariainen H, Majewski F (1988): Congenital scalpdefects with distal limb anomalies (Adams-Oliver syndrome): Report often cases and review of the literature. Am J Med Genet 31:99115.

    McMurray BR, Martin LW, Dignan PStJ, Fogelson MH (1977): Hereditaryaplasia cutis congenita and associated defects. Clin Pediatr (Phila) 16:610614.

    Merlob P, Sivan Y, Reissner SH (1984): Anthropometric measurements ofthe newborn infant (27 to 41 gestational weeks): Birth Defects 20:151.

    Scribanu N, Temtamy SA (1975): The syndrome of aplasia cutis congenitawith terminal transverse defects of limbs. J Pediatr 87:7992.

    Whitly CB, Gorlin JG (1991): Adams-Oliver syndrome revisited. Am J MedGenet 40:319326.

    Zapata HH, Sletten LJ, Pierpont ME (1995): Congenital cardiac malfor-mations in Adams Oliver syndrome. Clin Genet 47:8084.

    Adams-Oliver Syndrome 199


View more >