Alternative titles; symbols
SNOMEDCT: 721888002; ORPHA: 2036; DO: 0111550;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 18q11.2 | Scalp-ear-nipple syndrome | 181270 | Autosomal dominant | 3 | KCTD1 | 613420 |
A number sign (#) is used with this entry because scalp-ear-nipple syndrome (SENS) is caused by heterozygous mutation in the KCTD1 gene (613420) on chromosome 18q11.
Scalp-ear-nipple syndrome is characterized by aplasia cutis congenita of the scalp, breast anomalies that range from hypothelia or athelia to amastia, and minor anomalies of the external ears. Less frequent clinical characteristics include nail dystrophy, dental anomalies, cutaneous syndactyly of the digits, and renal malformations. Penetrance appears to be high, although there is substantial variable expressivity within families (Marneros et al., 2013).
Finlay and Marks (1978) described a kindred with 10 persons over 5 generations showing an abnormality of the scalp, ears, and nipples. Although in part the scalp abnormality resembled that of aplasia cutis congenita, the syndrome appeared to be distinctive. The affected persons showed raised, firm nodules over the posterior aspect of the scalp, not covered by hair. The areas were raw at birth and healed during childhood. Skull x-rays were normal. Histologically there was an excess of collagenous connective tissue. The pinnae showed small, even rudimentary, tragus, antitragus, and lobule. The superior edge of the helix was 'turned over' to an exceptional degree. The nipples were rudimentary or absent. In the proposita, a 51-year-old woman, secondary sexual hair was scanty and the breasts had not enlarged during pregnancy, nor had lactation occurred. She was diabetic as were several other members of her family.
Le Merrer et al. (1991) reported an infant girl, born of nonconsanguineous Moroccan parents, who at birth was noted to have complete absence of the nipples, a scalp defect, and unusual facial features, including cup-shaped ears with hypoplastic helices, telecanthus with a flat nasal bridge, narrow palpebral fissures with epicanthus, and puffy eyelids. The occipital scalp defect involved a slightly convex hairless area with thin, atrophic, and crumpled skin. Skull x-rays showed hypotelorism and a lacuna in the lambdoid area. Histologic examination of the scalp lesion showed fibrous tissue with vascular changes consistent with angiofibroma; no cerebral tissue was present. She also had bilateral camptodactyly of the fifth fingers and small first metacarpals, but there were no other skin anomalies or ectodermal defects. Renal ultrasound showed hypoplasia of the right kidney.
Edwards et al. (1994) described a family with 12 affected members in 4 generations, with instances of male-to-male transmission. Women had virtually complete aplasia of the breasts and a small skin dimple without any pigmentation instead of the normal nipple. Dental changes included widely spaced or missing secondary teeth. The ears were cupped or folded and stood out from the head. Axillary apocrine secretion and axillary hair growth were reduced. Fingernails were brittle. There was no generalized abnormality of sweating. Some patients had partial syndactyly of the third and fourth fingers, and complete cutaneous syndactyly of the second and third toes. Edwards et al. (1994) suggested that the family reported by Tuffli and Laxova (1983) had this disorder (see 129550). See 113700 for a discussion of athelia (absence of breasts and nipples).
Plessis et al. (1997) reported a 23-year-old woman who had a large scalp defect at birth, bilateral amastia, and hypoplastic ears. She also had facial dysmorphism, with telecanthus associated with subcutaneous lipomatosis, narrow palpebral fissures with epicanthus, and colobomata of the lower eyelids. Unilateral cataract and renal insufficiency secondary to bilateral renal hypoplasia were also present. Plessis et al. (1997) pointed out that the case reported by Le Merrer et al. (1991) had renal hypoplasia and that other reported cases had renal disease. They also noted that one member of the family reported by Edwards et al. (1994) had a unilateral cataract. Plessis et al. (1997) suggested that when a scalp defect is present, investigation of other signs, particularly renal hypoplasia and cataract, should be performed.
Picard et al. (1999) reported a father and daughter with characteristic features of the Finlay-Marks syndrome. In addition, the 12-month-old daughter was found to have a right pyeloureteral duplication, following an episode of pyelonephritis. The father had been diagnosed in infancy as having left renal agenesis associated with contralateral vesicoureteral reflux and double ureters and had been treated surgically. The authors suggested that renal and urinary tract abnormalities should be regarded as part of the syndrome.
Sobreira et al. (2006) reported a Brazilian boy with Finlay-Marks syndrome. Absence of nipples and a scalp defect were noted at birth. At age 7 years, physical examination showed prominent, hypoplastic ears with almost absent pinnae and folded helices. There was a large area of hairless, thin, atrophic, and crumpled skin in the occipital region of the scalp. Other features included epicanthus, anteverted nares, short columella, prognathism, and widely spaced upper central incisors. The extremities showed cutaneous syndactyly of the second and third toes and distal nail dysplasia of both the hands and feet. The patient also had bilateral coloboma of the iris, asymmetric pupils, and myopia. Intellectual development was normal. Sobreira et al. (2006) noted that ocular abnormalities had not previously been reported in patients with Finlay-Marks syndrome.
Baris et al. (2005) reported the case of a woman with hypothelia, mildly deformed ears, and mild cutaneous syndactyly of the hands and feet.
Al-Gazali et al. (2007) described 2 children in 2 sibships of an inbred Arab family with scalp cutis aplasia, which was raw at birth and healed gradually, abnormal ears, hypoplastic nipples, and facial dysmorphic features similar to those described in SEN syndrome. The children also had severe hypotonia and developmental delay, which had not been noted in previously reported cases. Al-Gazali et al. (2007) suggested that the disorder in these children may be a severe recessive form of SEN syndrome.
Baris et al. (2005) reviewed the literature and concluded that scalp-ear-nipple syndrome is an autosomal dominant condition.
Al-Gazali et al. (2007) suggested that there may be a recessive form of SEN syndrome which includes severe hypotonia and developmental delay.
Marneros et al. (2013) performed linkage analysis in a large 4-generation family with scalp-ear-nipple syndrome, originally described by Edwards et al. (1994), and obtained a pairwise maximum lod score (Zmax) of 2.94 with marker D18S53 (theta = 0.001). Haplotype analysis defined an approximately 42.9-Mb critical interval between D18S452 and D18S474.
In a large 4-generation family with scalp-ear-nipple syndrome, originally described by Edwards et al. (1994), and 2 additional unrelated families with the disorder, Marneros et al. (2013) performed exome sequencing and identified 3 heterozygous missense mutations in the KCTD1 gene (see, e.g., 613420.0001 and 613429.0003) that segregated with disease in each family. The mutations were confirmed by Sanger sequencing and were not found in the dbSNP database (v.134) or in approximately 1,530 control exomes from the NHLBI Exome Sequencing Project. Sanger sequencing of KCTD1 in 9 affected individuals from 7 additional unrelated families with SEN syndrome, 4 of which had previously been reported (Le Merrer et al., 1991; Plessis et al., 1997; Picard et al., 1999; and Sobreira et al., 2006), revealed 7 more heterozygous missense mutations (see, e.g., 613420.0002 and 613420.0004-613420.0008). Marneros et al. (2013) noted that the clinical characteristics of individuals with different KCTD1 mutations were similar to one another, despite the variable expressivity of SEN syndrome within families.
Al-Gazali, L., Nath, R., Iram, D., Al Malik, H. Hypotonia, developmental delay and features of scalp-ear-nipple syndrome in an inbred Arab family. Clin. Dysmorph. 16: 105-107, 2007. [PubMed: 17351354] [Full Text: https://doi.org/10.1097/MCD.0b013e3280147217]
Baris, H., Tan, W.-H., Kimonis, V. E. Hypothelia, syndactyly, and ear malformation--a variant of the scalp-ear-nipple syndrome?: case report and review of the literature. Am. J. Med. Genet. 134A: 220-222, 2005. Note: Erratum: Am. J. Med. Genet. 136A: 114-115, 2005. [PubMed: 15712197] [Full Text: https://doi.org/10.1002/ajmg.a.30612]
Edwards, M. J., McDonald, D., Moore, P., Rae, J. Scalp-ear-nipple syndrome: additional manifestations. Am. J. Med. Genet. 50: 247-250, 1994. [PubMed: 8042668] [Full Text: https://doi.org/10.1002/ajmg.1320500307]
Finlay, A. Y., Marks, R. An hereditary syndrome of lumpy scalp, odd ears and rudimentary nipples. Brit. J. Derm. 99: 423-430, 1978. [PubMed: 708615] [Full Text: https://doi.org/10.1111/j.1365-2133.1978.tb06182.x]
Le Merrer, M., Renier, D., Briard, M. L. Scalp defect, nipples absence and ears abnormalities: another case of Finlay syndrome. Genet. Counsel. 2: 233-236, 1991. [PubMed: 1799422]
Marneros, A. G., Beck, A. E., Turner, E. H., McMillin, M. J., Edwards, M. J., Field, M., Sobreira, N. L. de M., Perez, A. B. A., Fortes, J. A. R., Lampe, A. K., Giovannucci Uzielli, M. L., Gordon, C. T., and 13 others. Mutations in KCTD1 cause scalp-ear-nipple syndrome. Am. J. Hum. Genet. 92: 621-626, 2013. [PubMed: 23541344] [Full Text: https://doi.org/10.1016/j.ajhg.2013.03.002]
Picard, C., Couderc, S., Skojaei, T., Salomon, R., de Lonlay, P., Le Merrer, M., Munnich, A., Lyonnet, S., Amiel, J. Scalp-ear-nipple (Finlay-Marks) syndrome: a familial case with renal involvement. (Letter) Clin. Genet. 56: 170-172, 1999. [PubMed: 10517259] [Full Text: https://doi.org/10.1034/j.1399-0004.1999.560216.x]
Plessis, G., Le Treust, M., Le Merrer, M. Scalp defect, absence of nipples, ear anomalies, renal hypoplasia: another case of Finlay-Marks syndrome. Clin. Genet. 52: 231-234, 1997. [PubMed: 9383029] [Full Text: https://doi.org/10.1111/j.1399-0004.1997.tb02553.x]
Sobreira, N. L. de M., Brunoni, D., Cernach, M. C. S. P., Perez, A. B. A. Finlay-Marks (SEN) syndrome: a sporadic case and the delineation of the syndrome. (Letter) Am. J. Med. Genet. 140A: 300-302, 2006. [PubMed: 16411189] [Full Text: https://doi.org/10.1002/ajmg.a.31063]
Tuffli, G. A., Laxova, R. New, autosomal dominant form of ectodermal dysplasia. Am. J. Med. Genet. 14: 381-384, 1983. [PubMed: 6837633] [Full Text: https://doi.org/10.1002/ajmg.1320140219]