American Journal of Medical Genetics 32266-267 (1989)
Letter to the Editor
Congenital Scalp Defects With Distal Limb Anomalies (Adams-Oliver Syndrome-McKusick 10030): Further Suggestion of Autosomal Recessive Inheritance
To the Editor:
I read with interest the article by Koiffmann et al.,  regarding aplasia cutis congenita (ACC) with dis- tal limb anomalies. The authors reported three mem- bers of a sibship born to consanguineous parents who demonstrated both ACC and variable hypoplasia of the fingers and toes.
The authors discuss the recognized association of ACC with limb defects and cite five previous pedigrees in the literature. Because of the occurrence of the disorder in a single sibship born to first cousins, the authors raise the possibility of autosomal recessive inheritance as opposed to autosomal dominant inheritance.
Aplasia cutis congenita in association with limb ab- normalities has been reported numerous times in the literature [Sybert, 1985; Lynch and Kahn, 1970; Adams and Oliver, 1945; Kahn and Olmedo, 1950; Scribanu and Temtamy, 1975; Burton et al., 1976; McMurray et al., 1977; Bonafede and Beighton, 1979; Fryns and Van den Berghe, 19791. Limb abnormalities seen in association with ACC include hypoplastic fingernails, cutaneous syndactyly, bony syndactyly, transverse reduction de- fects, zygodactyly, ectrodactyly, polydactyly, and brachy- dactyly. Limb involvement is often asymmetric.
In the majority of familial cases, the inheritance pat- tern was most consistent with an autosomal dominant gene with reduced penetrance and extremely variable expression. For example, in one of the pedigrees I re- ported [Sybert, 19851 in which zygodactyly and ACC were seen, obligate heterozygotes manifested none, one, the other, or both of the defects, and the severity was quite wide among those individuals who manifested the disorder.
Although a variety of limb defects have been reported in association with ACC of the scalp, the type of limb defect appears to be specific for each family, and there is
Received for publication September 6, 1988. Address reprint requests to Virginia P. Sybert, Medical Ge-
netics, POB (25371, CHMC, 4800 Sandpoint Way NE, Seattle, WA 98105.
no intrafamilial variation in the general category of limb defect. There are numerous sporadic reports of ACC in association with limb defects; they may repre- sent nongenetic syndromes as well as new mutations and failure to adequately examine other family members.
While it is certainly possible that the family reported by Koiffmann et al.  does represent autosomal recessive inheritance, I agree with the authors that au- tosomal dominant inheritance cannot be rule out.
In the last statement of the article, the authors cau- tion that physicians should prepare to treat promptly scalp lesions of ACC. These lesions rarely require ther- apy and usually heal rather quickly. The only exception to this is when the superior sagittal sinus is exposed. For those infants, prompt surgical intervention is nec- essary. Even with very large scalp defects, if the supe- rior sagittal sinus is not exposed, rapid healing without need for grafting usually occurs.
In the same issue of the journal, Toriello et al.  reported a family with scalp and limb defects with cutis marmorata telangectatica congenita. The authors refer to my study [Sybert, 19851 as reporting instances of ACC and limb defects consistent with autosomal recessive inheritance. Among the 14 families included in my study, all of the pedigrees for individuals with scalp defects and limb abnormalities were consistent with au- tosomal dominant inheritance or appeared to be spo- radic. While there are some reports in the literature of ACC of the body wall occuring in sibships consistent with autosomal recessive inheritance [Rauschkolb and Enriquez, 1962; Scott, 1967; Freire-Maia et al., 19801, in none of the families that I reported was there evidence for autosomal recessive inheritance, either of ACC of the scalp with limb defects or ACC of the body wall with limb defects. In two of my families, isolated ACC oc- curred in sibs, and both parents were reported to be normal. In one, the parents were unavailable for exam- ination; in the other, both parents were normal on examination.
0 1989 Alan R. Liss, Inc.
Congenital Scalp Defects 267
Koiffmann CP, Wajntal A, Huyke BJ, Castro RM (1988): Congenital scalp skull defects, with distal limb anomalies (Adam-Oliver Syn- drome-McKusick 10030): Further suggestion of autosomal reces- sive inheritance. Am J Med Genet 29:263-268.
Lynch PJ, Kahn EA (1970): Congenital defects of the scalp: A surgical approach to aplasia cutis congenita. J Neurosurg 33:198-202.
McMurray BR, Martin LW, Dignan PStJ, Fogelson MH (1977): Hered- itary aplasia cutis congenita and associated defects: Three in- stances in one family and a survey of reported cases. Clin Pediatr 16:610-614.
Rauschkolb RR, Enriquez S1 (1962): Aplasia cutis congenita. Arch Dermatol 8654-57.
Scott FP (1967): Congenital skin defects. Dermatologica 13584-89. Seribanu N, Temtamy SA (1975): The syndrome of aplasia cutis congen-
ita with terminal transverse defects of limbs. J Pediatr 87:79-82. Sybert VP (1985): Aplasia cutis congenita: A report of 12 new families
and review of the literature. Pediatr Dermatol 3:l-14. Toriello HV, Graft RG, Florentine MF, Lacina S, Moore WD (1988):
Scalp and limb defects with cutis marmorata telangiectatica con- genita: Adams-Oliver syndrome? Am J Med Genet 29269-276.
It is my belief that most, if not all, instances of isolated ACC of the scalp are the result of an autosomal domi- nant gene, that ACC of the body wall + limb defects is an extremely heterogeneous group among which there may be inherited disorders of all Mendelian types as well as sporadic and nongenetic causes, and that ACC limited to the scalp in association with limb defects is most often inherited as an autosomal dominant. This last category obviously contains either allelic or nonal- lelic disorders.
I would refer your readers to both Sybert  and Frieden  for comprehensive reviews of this subject.
REFERENCES Adams FH, Oliver CP (1945): Hereditary deformities in man due to
arrested development. J Hered 36:2-7. Bonafede RP, Beighton P (1979): Autosomal dominant inheritance of
scalp defects with ectrodactyly. Am J Med Genet 3:35-41. Burton BK, Hauser L, Nadler HL (1976): Congential scalp defects with
distal limb anomalies-report of a family. J Med Genet 13:466-468. Freire-Maia N, Pinheiro M, Ortega CC (1980): Recessive aplasia cutis
congenita of the limbs. J Med Genet 17:123-126. Frieden I (1986): Aplasia cutis congenita: A clinical review and pro-
posal for classification. J Am Acad Dermatol 14:646-660. Fryns JP, Van den Berghe H (1979): Congenital scalp defects associated
with postaxial polydactyly. Hum Genet 49217-219. Kahn EA, Olmedo L (1950): Congenital defect of the scalp: With a note
on closure of large scalp defects in general. Plast Reconstr Surg 6:435-440.
Virginia P. Sybert, Department of Pediatrics (Medical Genetics) Adjunct Associate Professor, Department of Medicine (Dermatology) Childrens Hospital and Medical Center,
University of Washington School of
Edited by James F. Reynolds