Adermatoglyphia

A number sign (#) is used with this entry because of evidence that adermatoglyphia (ADERM) is caused by heterozygous mutation in the SMARCAD1 gene (612761) on chromosome 4q22.

Two overlapping syndromes involving adermatoglyphia, Basan syndrome (BASAN; 129200) and Huriez syndrome (HRZ; 181600), are also caused by mutation in the SMARCAD1 gene.

Description

Adermatoglyphia is characterized by the lack of epidermal ridges on the palms and soles, which results in the absence of fingerprints, and is associated with a reduced number of sweat gland openings and reduced sweating of palms and soles (summary by Nousbeck et al., 2011).

Also see Naegeli-Franceschetti-Jadassohn syndrome (NFJS; 161000) and dermatopathia pigmentosa reticularis (DPR; 125595), 2 closely related autosomal dominant ectodermal dysplasia syndromes that clinically share complete absence of dermatoglyphics and are caused by heterozygous nonsense or frameshift mutations in the KRT14 gene (148066).

Clinical Features

Burger et al. (2011) reported a 29-year-old woman who presented because of recurrent difficulty at immigration checkpoints due to absent fingerprints. On examination, epidermal ridges were completely missing from her fingers, toes, palms, and soles, and the creases of her palms and soles also showed abnormal patterns. Her skin and hair appeared normal, with only mild hyperkeratosis of the hands and calluses on weight-bearing areas. She had no history of blistering, no subjective problems with the skin of her hands or feet, and was not more sensitive to heat or cold than unaffected persons. Her nails showed slight clubbing without nail plate dystrophy, and there was mild clinodactyly of both fifth fingers. A sweat test of the hands revealed a strongly reduced ability for transpiration, with small areas showing a positive result. A biopsy of fingertip skin showed a reduced number of sweat gland openings. Her family pedigree revealed that absence of fingerprints was inherited in an autosomal dominant fashion, with 10 affected individuals over 4 generations. There was no history of multiple milia on the chin in infancy, and no affected individuals had developed fissures or bullous lesions on the fingers or feet.

Nousbeck et al. (2014) studied 3 unrelated families with adermatoglyphia. In a 4-generation Swedish family, all 5 affected members had absence of fingerprints from birth. In a 4-generation family of Austrian ancestry, all 6 patients reported absence of recognizable epidermal ridges and difficulty in grasping and holding items with their hands. The male proband of an American family with German, Dutch, English, and Scottish ancestries lacked epidermal ridges and also reported plantar calluses, palmoplantar hypohidrosis, difficulty in grasping and holding, and fingernail pterygia.

Mapping

In the 4-generation Swiss kindred with adermatoglyphia originally reported by Burger et al. (2011), Nousbeck et al. (2011) performed multipoint linkage analysis and obtained a lod score of 2.85 on marker rs1509948 on chromosome 4. Fine mapping and haplotype analysis refined the disease interval to a 1.5-Mb interval between markers D4S423 and D4S1560.

Molecular Genetics

In a 4-generation Swiss kindred with adermatoglyphia mapping to chromosome 4q, originally studied by Burger et al. (2011), Nousbeck et al. (2011) sequenced all coding and noncoding exons of the 17 genes located within the disease interval but found no mutations. However, further analysis revealed a heterozygous splice site mutation in the skin-specific SMARCAD1 short isoform (612761.0001) that segregated with disease in the family and was not found in 100 Swiss controls or in 100 Jewish controls.

In 3 unrelated families with adermatoglyphia, Nousbeck et al. (2014) sequenced the SMARCAD1 gene and identified 3 different heterozygous splice site variants (612761.0002-612761.0004), 1 of which (612761.0002) involved the same nucleotide as the mutation identified in the Swiss family (612761.0001) by Nousbeck et al. (2011). All 3 mutations were predicted to abolish a conserved donor splice site adjacent to the 3-prime end of a noncoding exon unique to the skin-specific SMARCAD1 isoform. In the Swedish family, the only family for which multiple DNA samples were available, the mutation segregated completely with disease; none of the 3 mutations were found among 8,000 individual sequences from the 1000 Genomes Project and NHLBI Exome Sequencing Project databases.

Exclusion Studies

In a 4-generation pedigree with adermatoglyphia, Burger et al. (2011) analyzed the candidate gene keratin-14 (KRT14; 148066) but did not find any mutations.