HATS Syndrome: Hemimaxillary Enlargement, Asymmetry of the Face, Tooth Abnormalities, and Skin Findings

Case Report

A 14-year-old adolescent boy presented to the dermatology clinic at our institution for evaluation of a hyperpigmented hairy patch on the right side of the face that had been present since birth. The patient reported the lesion originally had involved the right cheek, neck, and back but had gradually expanded to include the right side of the upper lip and oral mucosa. His medical history was remarkable for acne, which was currently being managed with topical treatments. There was no family history of similar conditions. There were no mental or developmental deformities since birth.

Physical examination revealed a hyperpigmented patch with hypertrichosis on the right side of the body involving the back, neck, and cheek (Figure 1), as well as hyperpigmentation involving the right side of the upper lip and oral mucosa (Figure 2A). Slight facial asymmetry also was noted. Dental examination revealed irregular spacing and decreased growth of the teeth on the right side of the mouth (Figure 2B).

^{Figure 1. Hyperpigmented hairy patch on the right cheek (Becker nevus) in a patient with hemimaxillary enlargement, asymmetry of the face, tooth abnormalities, and skin findings (HATS syndrome).}

Figure 2. Some hyperpigmentation involving the oral mucosa on the right side (A) and dental abnormalities (B).

A biopsy of the hyperpigmented patch on the back revealed mild regular acanthosis, basal hypermelanosis, slight papillomatosis, and hair structures within the dermis with features that were consistent with a Becker nevus. A dental radiograph demonstrated hyperplasia of the right maxillary alveolus and basal bone area with 2 missing permanent teeth (fourth and fifth premolars)(Figure 3). Computed axial tomography revealed enlargement of the maxillary bone on the right side.

^{Figure 3. Dental radiograph demonstrated hyperplasia of the right maxillary alveolus and basal bone area with 2 missing permanent teeth (fourth and fifth premolars).}

The constellation of clinical, histopathologic, and radiologic findings was consistent with a diagnosis of hemimaxillary enlargement, asymmetry of the face, tooth abnormalities, and skin findings (HATS syndrome). The treatment plan involved surgical modification of the maxillary bone to correct the hyperplasia on the affected side and implanting 2 artificial premolars. Additionally, laser therapy using a Q-switched ruby laser, frequency-doubled Nd:YAG, 1550-nm erbium-doped fiber laser, or 755-nm alexandrite laser was considered to treat the hyperpigmentation associ-ated with the Becker nevus.

Comment

HATS syndrome is a rare, local developmental defect involving the first and second branchial arches. It generally is detected at birth or in early childhood and is associated with unilateral abnormalities of the bones, teeth, gums, and skin. It is more common in boys than girls (1.8:1.0 ratio), with an age range of 2 to 28 years; there is a peak in the first decade of life.¹ It was first described by Miles et al² in 1987 in a case of congenital mild facial asymmetry, unilateral enlargement of the maxillary gingiva and alveolar bone, hypoplastic teeth, and hypertrichosis in the affected area. The investigators at that time suggested the term hemimaxillofacial dysplasia (HD). In 1990, Danforth et al³ reported 8 additional cases with similar features but without known skin changes; they proposed the term segmental odontomaxillary dysplasia (SOD). In 1996, Desalvo et al⁴ reported a case of SOD involving a 7-year-old girl with an area of hypopigmentation of the lip on the affected side, and Packota et al⁵ described the radiographic features of 12 cases of SOD. In subsequent years, other cases of HD or SOD were reported in the literature.^1,6-16 In 2004, Welsch and Stein¹⁷ reported 1 patient with a Becker nevus of the skin and recommended the acronym HATS. Armstrong et al¹⁸ reported 2 cases of SOD with new histopathologic findings of the teeth (eg, fibrous enlargement of the pulps, an irregular pulp-dentin interface displaying many pseudoinclusions, pulp stones). In 2008, Porwal et al¹⁹ reported a case of HD in which maxillary hypoplasia rather than hyperplasia was noted, which emphasized the variability of the maxillary dysplasia. Koenig et al²⁰ reported a case of SOD with facial hypertrichosis, commissural lip clefting, and hyperlinear palms. Bhatia et al²¹ reported another case of SOD with a new finding of unilateral ectopic eyelashes.

The etiology remains unknown, but theories include an alteration that occurs in utero or in in-fancy; the possibility of a systemic or endocrine aberration; a postzygotic mutation resulting in genotypic and phenotypic mosaicism of bone and skin, similar to McCune-Albright syndrome; and viral or bacterial infection along the branches of the maxillary division of the trigeminal nerve.^1,15 Bone defects include unilateral enlargement of the maxillary alveolar process and thickening of the vertically oriented trabeculae, which is detected radiographically. A reduction in size of the maxillary sinus and nasal airway was reported in about one-half of cases¹ and can be detected easily by computed tomography scanning. Missing permanent premolar teeth, tooth shape abnormalities, delayed eruption of teeth, abnormal spacing of teeth, hypoplastic teeth, enlarged teeth, and gingival thickening also are common oral findings.¹ The skin manifestations of HATS syndrome are not static but progress well into adolescence¹⁵ and can include facial asymmetry, hypertrichosis, Becker nevus, hairy nevus, lip hypopigmentation, discontinuity of the vermilion border, depression of the cheek, and facial erythema.¹⁷