Acromegaloid Facial Appearance Syndrome

Clinical Features

In many members of a kindred through at least 5 generations, Hughes et al. (1985) described a syndrome of acromegaloid facial features: thickened lips (without a true 'double lip'), overgrowth of the intraoral mucosa resulting in exaggerated rugae and frenula, and thickened upper eyelids leading to narrow palpebral fissures (blepharophimosis). The nose tended to be bulbous. The hands were large and doughy without clubbing. Highly arched eyebrows were striking in published photographs. There was no evident impairment of general health. Pachydermoperiostosis (167100), Ascher syndrome (109900), and multiple neuroma syndrome (162300) were considered in the differential diagnosis.

Dallapiccola et al. (1992) reported a family with the disorder in 2 generations. Five affected persons, a mother and 4 children, showed a striking resemblance to the patients reported by Hughes et al. (1985). They had progressively coarsening acromegaloid facial appearance, narrow palpebral fissures, bulbous nose, and thickening of the lips and intraoral mucosa, resulting in exaggerated rugae of the tongue and frenula. The patients had increased birth weight and dull mentality. Tapering fingers in the mother and 1 daughter, somewhat like those in the Coffin-Lowry syndrome (303600), were pictured.

Kini and Clayton-Smith (2004) reported a patient with AFA syndrome. The phenotype included a progressively coarse acromegaloid-like facial appearance with thickening of the lips and gums and severe learning difficulties. The patient's paternal grandmother also showed some features of the condition, suggesting autosomal dominant inheritance with incomplete penetrance in this family.

Inheritance

The pedigree pattern in families with AFA syndrome reported by Hughes et al. (1985) and Kini and Clayton-Smith (2004) was consistent with autosomal dominant inheritance.

Mapping

In a family with acromegaloid facial appearance syndrome, Hughes et al. (1985) found low positive lod scores for linkage between the disorder and Rh and PGM1 (on 1p), GLO (on 6p), IGHG and PI (on 14q), and HP (on 16q).