ECTODERMAL DYSPLASIA, ANHIDROTIC, WITH CLEFT LIP/PALATE OROFACIAL CLEFT 8, INCLUDED
CLEFT LIP WITH OR WITHOUT CLEFT PALATE, NONSYNDROMIC, 8, INCLUDED
OFC8, INCLUDED
RHS
Rapp and Hodgkin (1968) described mother, son, and daughter with anhidrotic ectodermal dysplasia, cleft lip, and cleft palate. The combination had not previously been recorded. The nose was unusually narrow and the mouth small. Similar cases were reported ... Rapp and Hodgkin (1968) described mother, son, and daughter with anhidrotic ectodermal dysplasia, cleft lip, and cleft palate. The combination had not previously been recorded. The nose was unusually narrow and the mouth small. Similar cases were reported by Summitt and Hiatt (1971) and Wannarachue et al. (1972). Silengo et al. (1982) reported affected mother and daughter. The child had pili torti; the scalp hair was coarse, dry, and wiry. Microscopically, it showed twisting. The mother, who was bald, had had similar hair as a child. The same family was reported by Stasiowska et al. (1981). Montes-G and Salinas (1986) reported 2 families: in one, the mother and 2 daughters by different fathers were affected; in the other, 5 persons in 4 generations were affected, with male-to-male transmission. Characteristics of the hair were detailed. Hypodontia, changes in the fingernails, and hypospadias in males are also features. Salinas and Montes-G (1988) gave further information on 6 personally examined patients with RHS plus 4 additional family members with documentation strongly suggesting that they were affected. Submucous cleft or cleft of the uvula was found in some. The hair was uncombable and wiry and progressed to alopecia in adulthood. Ptosis, atretic ear canals, and dysplastic eustachian orifices were also described as possible features. They claimed to have observed male-to-male transmission for the first time. They suggested that the characteristic hair change is pili canaliculi; under the scanning electron microscope and polarizing microscope, hairs showed canal-like depressions running the length of the axis. Schroeder and Sybert (1987) described a case. Santos et al. (1990) described a case of apparent new mutation. Rodini et al. (1990) observed 11 affected persons in 4 generations of a Brazilian family. Severity ranged from isolated trichodysplasia (sparse, brittle, and dry hair) to the full-blown picture. Tear duct anomalies were present in several. Breslau-Siderius et al. (1991) reported a Dutch family with 4 affected persons in 3 generations. Walpole and Goldblatt (1991) described the clinical features in 4 members of a 3-generation family with Rapp-Hodgkin hypohidrotic ectodermal dysplasia. Moerman and Fryns (1996) described a mother with manifestations consistent with the Rapp-Hodgkin type of ectodermal dysplasia and her malformed newborn son with ectrodactyly, ectodermal dysplasia, cleft palate, and bilateral cystic and obstructive ureteroceles with hydroureters and cystic renal dysplasia as described in the EEC syndrome (EEC1; 129900). They suggested that these may be fundamentally the same disorder. The newborn died at 1 day of age. Autopsy demonstrated severe pulmonary hypoplasia. The baby also showed filiform adhesions of the eyelids (ankyloblepharon filiforme adnatum). The association of ankyloblepharon, ectodermal defects, and clefting (106260) is referred to as the AEC syndrome or Hay-Wells syndrome. See also 106250 for the association of ankyloblepharon with cleft palate.
In a 14-year-old Thai boy diagnosed with Rapp-Hodgkin syndrome, who had the characteristic facies, microsomia, obstructed lacrimal puncta, and palmoplantar keratoderma but no ankyloblepharon, Kantaputra et al. (2003) identified heterozygosity for a missense mutation (S545P; 603273.0019) in the ... In a 14-year-old Thai boy diagnosed with Rapp-Hodgkin syndrome, who had the characteristic facies, microsomia, obstructed lacrimal puncta, and palmoplantar keratoderma but no ankyloblepharon, Kantaputra et al. (2003) identified heterozygosity for a missense mutation (S545P; 603273.0019) in the TP63 gene. Kantaputra et al. (2003) stated that this was the first genetic abnormality to be described in RHS, and noted that this provides molecular data to support the clinically observed overlap between EEC, AEC, and RHS. In 2 unrelated patients with features consistent with Rapp-Hodgkin syndrome, Bougeard et al. (2003) identified heterozygosity for mutations in the TP63 gene, R279H (603273.0007) and 1709delA (603273.0016), respectively. The R279H mutation had previously been found in 4 families with EEC3 (604292). In 2 sibs and their mother who had been diagnosed with RHS, Dianzani et al. (2003) identified a 1-bp deletion in the TP63 gene (603273.0017). The mother's clinical history revealed that she had a slight ankyloblepharon on the right eye at birth which was surgically treated; Dianzani et al. (2003) suggested that AEC and RHS are the same clinical entity. In a patient with AEC previously described by Bertola et al. (2000), Bertola et al. (2004) identified an ile510-to-thr mutation in the TP63 gene (603273.0018). They identified the same mutation in a patient with RHS and concluded that AEC and RHS represent variable expression of a single genetic disorder. In a 4-year-old Thai girl with nonsyndromic orofacial cleft, Leoyklang et al. (2006) identified an apparently pathologic mutation in the TP63 gene (603273.0021). In a 42-year-old woman and her mother, who had Rapp-Hodgkin syndrome associated with Groenouw-type corneal dystrophy (see 121900) and premature menopause at ages 28 and 35 years, respectively, Holder-Espinasse et al. (2007) identified heterozygosity for a 1-bp deletion in the TP63 gene (603273.0025). The affected maternal grandmother had premature menopause at 28 years of age, and an affected deceased older sister also had Groenouw-type corneal dystrophy. The authors stated that this was the first report of these additional age-related features in RHS. In an 11-year-old boy who displayed an overlapping phenotype with features of both AEC and RHS, Prontera et al. (2008) identified heterozygosity for an 11-bp duplication in the TP63 gene (603273.0027). The authors stated that their findings confirmed the hypothesis that AEC and RHS are variable expressions of a single genetic disorder, and suggested that intermediate phenotypes are possible.