Aplasia Cutis Congenita, Nonsyndromic
A number sign (#) is used with this entry because of evidence that nonsyndromic aplasia cutis congenita (ACC) is caused by heterozygous mutation in the BMS1 gene (611448) on chromosome 10q11. One such family has been reported.
DescriptionAplasia cutis congenita (ACC) is defined as congenital localized absence of skin. The skin appears as a thin, transparent membrane through which the underlying structures are visible. The location is usually on the scalp (Evers et al., 1995). Approximately 20 to 30% of cases have underlying osseous involvement (Elliott and Teebi, 1997). Autosomal dominant inheritance is most common, but recessive inheritance has also been reported.
Cutaneous aplasia of the scalp vertex also occurs in Johanson-Blizzard syndrome (243800) and Adams-Oliver syndrome (AOS; 100300). A defect in the scalp is sometimes found in cases of trisomy 13 and in about 15% of cases of deletion of the short arm of chromosome 4, the Wolf-Hirschhorn syndrome (WHS; 194190) (Hirschhorn et al., 1965; Fryns et al., 1973).
Evers et al. (1995) provided a list of disorders associated with aplasia cutis congenita, classified according to etiology. They also tabulated points of particular significance in history taking and examination of patients with ACC.
Clinical FeaturesTisserand-Perrier (1953) reported a 3-generation family with aplasia cutis congenita restricted to the skull vertex. Parent and child were affected in at least 3 families and sibs and cousins in others (Hodgman et al., 1965). Cutlip et al. (1967) reported affected mother and child. Pap (1970) described 4 persons in 3 generations. Deeken and Caplan (1970) described a father and 2 sons, who had 2 reportedly affected collateral relatives. Their series also contained 2 pairs of affected sibs.
Anderson et al. (1979) reported a family with aplasia cutis congenita in 3, and possibly 4, generations in a total of 7 or 8 affected persons. In 4 of these there was also unilateral facial palsy and in 6 there was ear abnormality, usually lop ear. No male-to-male transmission was noted.
Stevenson and DeLoache (1988) reviewed the causes of ACC on the basis of 7 families, one of which had twins concordant for ACC. The authors speculated that the scalp defect 'marks the point of final separation of monozygous twins.' In their case, 1 twin had the typical ACC lesion, whereas the other had a slightly raised skin lesion at the same location.
Gucuyener et al. (1992) observed ACC in 3 sibs.
Dunn (1992) pointed out that litigation may be brought against obstetricians because parents believe their child's scalp was injured during surgical induction of labor or by a fetal scalp electrode.
Elliott and Teebi (1997) reported 2 unrelated families with vertical transmission of aplasia cutis congenita. The first family involved 3 generations of affected individuals. There was 1 instance of male-to-male transmission. The second family contained 2 affected half brothers with a common father. There was no apparent consanguinity and the family history was otherwise unremarkable. The father was not available for study.
Park et al. (1998) reported a newborn male with almost complete absence of skin and subcutaneous tissue associated with choanal atresia, syndactyly, imperforate anus, pulmonary hypoplasia, and other anomalies. The child was karyotypically normal.
Gnamey et al. (2010) reported a male infant with focal dermal hypoplasia (FDH; 305600) who also had an extensive area of aplasia cutis congenita of the scalp vertex, with cerebral structures visible through the defect. The patient died at 23 days due to neurologic complications. Gnamey et al. (2010) reviewed 18 previously reported cases of FDH and stated that this was the first in which there was associated aplasia cutis congenita.
Yagci-Kupeli et al. (2011) described a mother, son, and daughter with aplasia cutis congenita; a maternal uncle was reportedly affected. One of the children also had unilateral right hand preaxial polydactyly but no other clinical or radiologic limb defects, including reduction defects. The authors suggested that the family had ACC or a mild form of Adams-Oliver syndrome (see 100300) with preaxial polydactyly as a feature.
Marneros (2013) studied a 5-generation family segregating autosomal dominant ACC, in which affected individuals had localized absence of skin at the vertex and occipital area of the scalp that usually healed with a hypertrophic scar. No other congenital anomalies were present.
InheritanceDubosson and Schneider (1978) stated that ACC is usually inherited as a dominant trait.
Recessive inheritance was suggested by the findings in some families (Gedda et al., 1963; Dubosson and Schneider, 1978).
Fullana et al. (1995) demonstrated autosomal dominant inheritance of ACC in a 5-generation family with 12 affected members. Male-to-male transmission of ACC in a family reported by Elliott and Teebi (1997) supported autosomal dominant inheritance.
MappingIn a 5-generation family segregating autosomal dominant ACC, Marneros (2013) performed genomewide linkage analysis and found a single region on chromosome 10q11 with a lod score greater than 2. A maximum lod score of 2.709 was obtained between SNPs rs1359280 and rs7071514.
Molecular GeneticsIn an affected member of a 5-generation family segregating autosomal dominant ACC mapping to chromosome 10q11, Marneros (2013) performed whole-exome sequencing and identified a single nonsynonymous heterozygous variant within the linked region of the BMS1 gene that resulted in a missense mutation (R930H; 611448.0001). The mutation, which segregated with disease in the family, was not found in 100 ethnically and geographically matched controls.
Exclusion Studies
In 6 families with autosomal dominant isolated ACC, Marneros et al. (2013) screened the KCTD1 gene (613420) but found no pathogenic variants.