Sonography of focal facial dermal dysplasia

Focal facial dermal dysplasia (FFDD) refers to a group of rare disorders of development characterised by congenital, bilateral, symmetrical atrophic facial plaques. These developmental defects occur along embryonic fusion lines at the bitemporal (FFDD types I-III) or preauricular (FFDD type IV) region, resembling aplasia cutis congenita. FFDD type IV is a rare autosomal recessive condition that has been reported in 30 patients from 23 families to the best of our knowledge.1-11 While histologic abnormalities have been described, sonography is yet to be reported. We report siblings with FFDD type IV and the first sonographic features of any FFDD. A four-month-old male infant presented with two symmetric atrophic plaques on each cheek noted from birth (Figure 1A). He was an otherwise well infant with an uncomplicated prenatal course and delivery. His four-year-old sister was born with lesions of similar morphology, with three plaques on her right cheek and two plaques on her left cheek (Figure 1B). She was otherwise well, with no comorbidities and meeting all developmental milestones. Both children were of Syrian heritage with their parents distantly related. Based on the distribution of the lesions and inheritance pattern, the patients were diagnosed with FFDD type IV. Sonography of the four-month-old male demonstrated focal hyperechoic dermal lesions, without significant vascularity or involvement of the subcutis (Figure 2A). Sonography of the four-year-old female demonstrated well-circumscribed, hypoechoic dermal lesions, without internal vascularity or extension into the subcutis (Figure 2B). The family was provided with counselling regarding the fixed nature of the skin lesions, and the possibility of future offspring being affected. The merits of genetic testing were discussed, but given it was unlikely to change management, this was declined by the family. FFDD is a group of rare disorders of facial development, characterised by bilateral symmetrical atrophic plaques in the preauricular or temporal region.9 There are four subtypes of FFDD. The first three are characterised by bitemporal lesions, resulting from the defective fusion of frontonasal and maxillary prominences. FFDD type I (Brauer syndrome) typically exhibits an autosomal dominant inheritance pattern and is characterised by bilateral atrophic plaques, usually without dysmorphic facial features.9 FFDD type III (Setleis syndrome) presents with the most distinct phenotype, with bitemporal atrophic plaques and dysmorphic facial features including a low frontal hairline, distichiasis, paucity of lower eyelashes, periorbital oedema and a flattened nasal bridge.12 The inheritance pattern of FFDD type III has been reported as autosomal recessive in homozygous TWIST2 mutations or autosomal dominant in the genomic multiplication of chromosomal region 1p36.22p36.21.12 FFDD type II (Brauer-Setleis syndrome) is characterised by mixed features of both type I and type III with Setleis-like features and follows an autosomal dominant inheritance, albeit with variable expressivity and lack of penetrance.9 As opposed to the first three subtypes, FFDD type IV is characterised by preauricular lesions, which result from the defective fusion at the maxillary and mandibular prominences. Mutations of the CYP26C1 gene have been implicated in cases of FFDD type IV which typically exhibits an autosomal recessive inheritance.8 Patients with this subtype do not exhibit facial dysmorphism and typically possess normal intellect. FFDD type IV is rare, with only 30 patients from 23 families reported to the best of our knowledge.1-11 Other features that have been reported alongside FFDD type IV include buccal mucosal polyps, cleft lip/palate and congenital naevi.10 Histologically, FFDD lesions demonstrate similar features to aplasia cutis congenita: atrophic epidermis, reduced levels of fragmented elastic tissue, replacement of dermis with loose connective tissue and absence of adnexal structures and subcutaneous tissue.8 The kindred reported herein extends the reported experience of FFDD type IV and is the first to describe sonographic findings in any patient with FFDD. Sonography is being increasingly employed in dermatology as a readily accessible, non-invasive diagnostic investigation, usually available even in institutions with limited resources.13 As a painless, innocuous bedside investigation free of ionising radiation, it is particularly appealing in the paediatric setting and may obviate the need for biopsy or general anaesthesia. Differential diagnoses for FFDD include aplasia cutis congenita, congenital morphoea, sebaceous naevus, preauricular tags or pits, and scarring from intrauterine insults. Interestingly, the two cases we report had varied sonographic findings, despite having a presumed common genetic origin. It may be that sonographic findings in FFDD vary with time. For instance, paediatric morphoea demonstrates varying tissue echogenicity depending on the timing of the sonography, with inactive lesions more likely to present with isoechogenicity compared to active lesions in the inflammatory phase which are more likely to be hypo- or hyperechoic.14 Sonography may play a role in differentiating FFDD from its main differential diagnosis of aplasia cutis. In contrast with the well-circumscribed focal dermal lesions that we describe in FFDD, aplasia cutis presents with discrete thinning of the dermis, increased echogenicity in the upper hypodermis and paucity of sebaceous and apocrine glands.13 Sebaceous naevus demonstrates hypoechoic band-like lesions with epidermal thickening and multiple hyperechoic sebaceous glands within a thickened dermis.15 Developmental defects such as pre-auricular pits or sinuses may demonstrate focal depression of the epidermis with a normal or slightly hypoechoic dermis, or a narrow hypoechoic tract that extends through the dermis and sometimes hypodermis.16 Sonography is emerging as a promising, non-invasive diagnostic investigation in dermatology, particularly useful in paediatric cases. The siblings reported in this case series broaden the literature on this rare condition, and the inaugural sonographic findings of FFDD highlight the evolving role of ultrasound in dermatology. The authors are grateful to the University of New South Wales and Ego Pharmaceuticals for their support of Yaron Gu through the University of New South Wales Honours Research Support Bursary and the QV Healthcare Practitioner Student Scholarship, respectively. We are indebted to Dr Peter Hogan and Dr Bryan Barry for their expertise regarding the management of these siblings. Open access publishing facilitated by University of New South Wales, as part of the Wiley - University of New South Wales agreement via the Council of Australian University Librarians. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Yaron Gu has received a scholarship from Ego Pharmaceuticals. Deshan Sebaratnam has received consulting fees from Galderma, AbbVie, Amgen, Pfizer, Novartis, Janssen, Leo Pharma, Ego Pharmaceuticals, Viatris, and Sun Pharma, and material support from Candela Medical and Heine Optotechnik. The guardian of the siblings provided permission to use clinical information/photographic material for publication. The data that support the findings of this study are available from the corresponding author upon request.