Basan Syndrome

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

Mutation in the SMARCAD1 gene can also cause phenotypes with features overlapping those of Basan syndrome, including isolated adermatoglyphia (ADERM; 136000) and Huriez syndrome (HRZ; 181600).

Description

Complete congenital absence of dermatoglyphs is a rare syndrome characterized by autosomal dominant inheritance of the lack of ridges on palms and soles, neonatal acral blisters and facial milia, adult traumatic blistering and fissuring, absent or reduced sweating of palms and soles, and contracture of digits. Additional features may include single palmar transverse crease, palmoplantar keratoderma, and nail grooving (summary by Limova et al., 1993).

Clinical Features

Baird (1964) reported an Irish American family in which 13 persons in 3 generations showed absent dermal ridges. The affected persons all had transient congenital milia (small white papules, especially on the face, representing retention cysts). Some affected members also showed bilateral partial flexion contractures of the fingers and toes and webbing of the toes. The palms became rough, thick, and calloused with age and were prone to painful fissures in hot or cold weather. Children of school age tended to blister on the palms in hot weather. Hair, eyebrows, eyelashes, teeth, and nails were normal in affected individuals. Skin biopsy from an area lacking dermal ridges showed mild hyperkeratosis, lack of skin appendages except for a few sweat glands, and a few focal infiltrates of lymphocytes in the upper dermis. Although the sweat glands and their ducts appeared normal in configuration, nowhere were they observed to actually open upon the surface. There was some acanthosis with irregularity of the rete pegs in their downward proliferation, and many of the collagen bundles in the dermis were coarse or twisted, as in scar tissue. In addition, capillaries were abnormally numerous in the dense collagen of the dermis. Baird (1985) stated that the family reported by Ludy (1944) was almost certainly the same as the one he later reported in more detail.

Basan (1965) reported a family in which persons of both sexes in 3 generations were affected. Male-to-male transmission was noted. Jorgenson (1974) reported a 5.5-year-old girl with this abnormality whose mother and grandmother were identically affected.

Reed and Schreiner (1983) described a 5-generation Irish American family with adermatoglyphia. The kindred was ascertained through a newborn male who had congenital milia on the chin, vesicular/bullous lesions on the fingers and soles, no detectable dermal ridge patterns, and no sweat gland openings on the palms or soles. At 1 week of age, the milia were regressing and the skin lesions were dry and healing. Follow-up examination at 15 months of age revealed smooth, dry volar skin with sweating absent from palms and soles. His nails were rough and transversely grooved, with some longitudinal ridges. The patient's affected father, paternal aunt, and paternal grandmother were available for examination: all 3 lacked sweating on the palms and soles, and their hands had a leatherlike texture, with tapered fingertips and nails that were grooved both horizontally and vertically with some vertical splits; transverse palmar creases were present bilaterally in the aunt and unilaterally in the grandmother and father. The father had a history of milia at birth, whereas the aunt, who did not have milia, presented with blisters on the hands and feet. All 3 adults reported increased heat tolerance and painful fissures around the fingernails in cold weather. Dermatoglyphic studies revealed a lack of pattern in all affected individuals, although there was an apparent tendency to form short segment ridges in limited areas of the palm or sole. Reed and Schreiner (1983) noted that their patients shared some features with those reported by Baird (1964), but concluded that the 2 families had different entities due to the presence of contractures as well as the lack of blisters or nail abnormalities in the latter patients.

Limova et al. (1993) reported a 34-year-old woman of Swedish descent with absence of fingerprints, who in infancy had erosions of the hands that healed uneventfully and in childhood developed mild contractures of both fifth fingers. She reported difficulty with fine grasping and with dryness and fissuring of her fingertips. Her father and paternal grandmother were similarly affected. On examination, the patient's acral skin was slightly hyperkeratotic with normal flexion creases and increased fine wrinkling; the fingertips appeared tapered, smooth, and shiny without dermal ridges, and there were mild contractures of the fifth fingers. She had similar features on her feet. Microscopic examination of fingertip skin revealed an epidermis of normal appearance except for its flat surface and absence of acrosyringia. Rete ridges and dermal papillae were present. The dermis appeared normal except for a complete absence of eccrine glands and coils. Staining demonstrated a normal elastic tissue pattern, and electron microscopy of the dermoepidermal junction was normal. Limova et al. (1993) concluded that this phenotype probably represented a milder form of the trait reported by Baird (1964) and Reed and Schreiner (1983), rather than a different entity.

Cirillo-Hyland et al. (1995) studied descendants of the Irish-American family with adermatoglyphia originally reported by Baird (1964), observing the newborn daughter of a fourth-generation man from that kindred. The infant, who had facial milia that were most pronounced over the chin, also had fine white scaling on palms and soles and underdeveloped palmar creases with faint single transverse creases bilaterally. Dermatoglyphs were completely absent, and she had an intact 4 mm vesicle on her right middle finger and a superficial 2.5 cm erosion on her left heel. Her nails were excessively rounded and wide for the width of the digits, resulting in a clubbed appearance. There were single transverse grooves on all fingernails except the thumbs, and on all toenails. Both fifth fingers had clinodactyly with mild camptodactyly at the distal interphalangeal joints, and bilateral cutaneous syndactyly of the 3 middle toes was also noted. Other features included bilateral underdeveloped auricular cartilages with overfolded helices, excessive nuchal skin, diminished tearing, 2 sacral paraspinal dimples, and an asymmetric deep sacral crease. Hair and nipples were normal. The patient's father, who had a history of transient congenital facial milia, had complete absence of dermal ridges, cutaneous syndactyly of the 3 middle toes, and bilateral flexion contractures of all fingers and all but the great toes. Cirillo-Hyland et al. (1995) concluded that the congenital absence of dermal ridges, as seen in the patients described by Baird (1964), Basan (1965), Reed and Schreiner (1983) and Limova et al. (1993), likely represents a single disorder of ectodermal development with high penetrance and variable expression.

Marks et al. (2014) studied a 4-generation family with Basan syndrome in which 7 members were affected. The proband was a boy who presented at birth with congenital absence of skin from a large region of his left foot. Examination at 4 days of life showed a large healing erosion on the plantar aspect of his left foot and a few small erosions on the dorsal aspects of both hands and feet. In addition, he lacked dermatoglyphs on his distal fingers and toes, and had numerous milia on his nose and cheeks. A male first cousin presented with loss of skin from his left heel following his first bath; examination at age 1 month showed complete healing of the left foot, but dermatoglyphs were absent on finger pads and toes. There was also a profuse eruption of milia on his scalp, forehead, nose, and chin. Family history revealed 5 more affected individuals over 4 generations with congenital absence of dermatoglyphs and a history of profuse facial milia in the newborn period. Three also had rapidly healing neonatal acral bullae. In addition, the affected fathers of the proband and the affected cousin both reported multiple palmoplantar callosities and decreased sweating on the palms and soles in adulthood.

Li et al. (2016) studied a 4-generation Chinese family in which 8 members had Basan syndrome. All affected individuals exhibited lack of fingerprints, congenital facial milia, transient neonatal blistering of the skin of the fingers and soles, palmoplantar hypohidrosis, and digital contractures of variable severity. The 2 oldest patients had moderate to severe palmoplantar keratoderma, and the oldest also showed nail dystrophy. Hyperpigmented macules on the dorsum of the hands and feet were present in 5 of the affected individuals, and 7 had knuckle pads, ranging from mild to severe.

Inheritance

Autosomal dominant inheritance of this disorder was demonstrated in kindreds reported by Baird (1964), Basan (1965), Reed and Schreiner (1983), and Limova et al. (1993).

Mapping

By genomewide linkage analysis in a 4-generation Chinese family with Basan syndrome, negative for mutation in the KRT5 gene (148040), Li et al. (2016) mapped 2 regions of linkage on chromosome 4 with maximal lod scores of 3.01: 4p15.31-p14, between rs1378946 and rs1435378, and 4q13.2-q23, between rs6840820 and rs6818863. No other locus of suggestive linkage was detected.

Molecular Genetics

In affected members of a 4-generation family with Basan syndrome, Marks et al. (2014) identified heterozygosity for a splice site mutation in the SMARCAD1 gene (c.378+3A-T; 612761.0005). The mutation segregated with disease in the family and was not found in the 1000 Genomes Project database.

In affected members of a 4-generation Chinese family with Basan syndrome mapping to 2 regions of chromosome 4, Li et al. (2016) performed exome and whole-genome sequencing and identified heterozygosity for a different mutation involving the same donor splice site in the SMARCAD1 gene (c.378+1G-T; 612761.0001). The mutation segregated with the phenotype in the family and was not found in 100 controls or in the 1000 Genomes Project, HapMap 8, or dbSNP (build 135) databases. Noting that the same splice site mutation had previously been identified in a Swiss family with isolated adermatoglyphia by Nousbeck et al. (2011), Li et al. (2016) suggested that isolated adermatoglyphia and Basan syndrome might represent phenotypic variants of the same disease, and that environmental factors, ethnic differences, modifier genes, or polymorphic SMARCAD1 sequences might play a role in the phenotypes.

Exclusion Studies

In 2 affected members of a 4-generation family with Basan syndrome, Marks et al. (2014) sequenced all coding regions and splice junctions of the KRT14 gene (148066) but did not find any likely pathogenic sequence alterations or splice site variants.