The focal dermal dysplasias (FFDDs) are a group of related developmental defects characterized by bitemporal or preauricular skin lesions resembling aplasia cutis congenita. FFDD4 is characterized by isolated, preauricular skin lesions (summary by Slavotinek et al., 2013). ... The focal dermal dysplasias (FFDDs) are a group of related developmental defects characterized by bitemporal or preauricular skin lesions resembling aplasia cutis congenita. FFDD4 is characterized by isolated, preauricular skin lesions (summary by Slavotinek et al., 2013). For a classification and a discussion of genetic heterogeneity of FFDD, see FFDD1 (136500).
Prescott et al. (2006) described 3 unrelated children, a girl and 2 boys, with distinctive facial skin lesions present at birth, consisting of 2 to 3 well-circumscribed round or oval vesicular lesions, 0.5 cm to 1 cm in ... Prescott et al. (2006) described 3 unrelated children, a girl and 2 boys, with distinctive facial skin lesions present at birth, consisting of 2 to 3 well-circumscribed round or oval vesicular lesions, 0.5 cm to 1 cm in diameter, located along an arc on each cheek from the top of the ear to the corner of the mouth. The infant girl, born of healthy unrelated Flemish parents, had 3 skin lesions containing a small amount of fluid on each cheek as well as unilateral cleft lip and palate and a cutaneous hemangioma in the left palm. One of the infant boys, born of healthy unrelated Norwegian parents, had 2 preauricular lesions noted on both cheeks at birth; those deflated and were followed by eruption of a new, more medial, lesion on each cheek at 2 to 3 weeks of age. The lesions subsequently remained unchanged and were encircled by long, fine hairs. The other infant boy was born of healthy unrelated Dutch parents and had symmetric atrophic skin lesions on both cheeks at birth that persisted with a lanugo-like collar; he also had mildly cupped ears, a small chin, and a congenital nevus on the left foot. The girl and the Dutch boy had normal development, but the Norwegian boy had neurologic complications that were the sequelae of an unexplained left-sided intracranial perinatal hemorrhage. Microscopic examination of a biopsied lesion in the Norwegian boy showed fragmentation of elastic fibers with striation and a diffuse increase in mast cells in the dermis, consistent with nonreactive deep and superficial elastolysis. Cervantes-Barragan et al. (2011) classified the FFDD phenotype in the 3 sibs (2 boys and 1 girl) reported by Kowalski and Fenske (1992) as FFDD4. The parents were first cousins. Slavotinek et al. (2013) studied a 6-year-old girl and her 4-year-old brother who were born with bilateral blister-like lesions on the cheeks, extending from the ear down to the lateral commissures of the mouth, which filled with fluid daily during the first few years of life. Both sibs were later noted to have several intraoral polypoid lesions, measuring 1 cm to 2 cm, on the left buccal mucosa. At the time of examination, the girl's skin lesions were hypopigmented macules, whereas her brother's were rounded with a small center of cutis aplasia, bordered by a hyperpigmented rim with long thin fine hairs; the brother also had a small area of sparse hair growth in front of both ears. The remainder of the dermatologic examination was normal, except for numerous scattered dark brown nevi in the sister. She also had a history of multiple dental extractions and root canal surgery for dental caries. Their unrelated parents had normal skin and family history was negative for significant skin findings. Slavotinek et al. (2013) also studied an unrelated Belgian girl who at birth was noted to have symmetric preauricular ivory round-to-oval patches with an atrophic aspect; there were no other abnormalities, and the skin lesions remained stable after birth.
In a 6-year-old girl and her 4-year-old brother with focal facial dermal dysplasia who were negative for mutation in the TWIST2 gene (607556), Slavotinek et al. (2013) performed exome sequencing and identified compound heterozygosity for a duplication and ... In a 6-year-old girl and her 4-year-old brother with focal facial dermal dysplasia who were negative for mutation in the TWIST2 gene (607556), Slavotinek et al. (2013) performed exome sequencing and identified compound heterozygosity for a duplication and a missense mutation in the CYP26C1 gene (608428.0001 and 608428.0002), which were maternally and paternally inherited, respectively, and were not present in 2 unaffected sibs. Analysis of the CYP26C1 gene in 12 more FFDD patients revealed 3 patients with FFDD4 who were homozygous for the duplication: 1 was a Belgian girl, and the other 2 were a Flemish girl and a Norwegian boy who had previously been reported by Prescott et al. (2006).