Cayler Cardiofacial Syndrome

Clinical Features

Cayler (1967, 1969) reported 5 babies with unilateral partial facial palsy and ventricular septal defect. Nelson and Eng (1972) and Pape and Pickering (1972) noted that asymmetric crying facies was due to congenital hypoplasia of the depressor anguli oris muscle and reported other associated anomalies. Papadatos et al. (1974) described apparently autosomal dominant inheritance of congenital hypoplasia of the depressor anguli oris muscle. The effect results in asymmetry of the lower lip, especially evident in smiling or crying.

In India, Singhi et al. (1980) found a frequency of 6.3 per 1,000 neonates. Two of the 10 affected neonates had congenital heart disease. Four of the 10 mothers of probands and 3 of 12 sibs had the same anomaly.

Silengo et al. (1986) described association with microcephaly with or without mental retardation in several members of 3 generations of a family.

Lin et al. (1997) evaluated associated anomalies in 50 infants or children with hypoplasia of the depressor anguli oris muscle and found accompanying anomalies in 35 (70%). These included anomalies of the head and neck (48%), heart (44%), skeleton (22%), genitourinary tract (24%), central nervous system (10%), gastrointestinal tract (6%), and miscellaneous minor anomalies (8%). In 22 of the 50 patients, at least 2 associated systemic anomalies were found. Failure to thrive and psychomotor retardation were found in 5 (10%) and 3 (6%) patients, respectively, on follow-up. Three infants died neonatally of severe heart disorders, and another died of central nervous system anomalies.

Caksen et al. (2004) reviewed 35 cases of asymmetric crying facies (28 children and 7 adults) and found additional abnormalities in 16 (45%) of them, including cerebral and cerebellar atrophy, mental and motor retardation, cranial bone defects, facial dysmorphism, musculoskeletal abnormalities, and genitourinary anomalies.

Shimasaki et al. (2004) reported a Japanese girl with features consistent with branchiootic syndrome (BOS1; 602588), including bilateral hearing impairment, preauricular pits, cupped ears, and bilateral cysts over the sternocleid muscle. A mutation was identified in the EYA1 gene (601653.0016), consistent with that diagnosis. The child also had features of the Cayler cardiofacial syndrome, including asymmetric face when crying and a large patent ductus arteriosus. The patient's mother had symmetric facial features, but moderate hearing loss, preauricular pits, and a right cervical sinus, all consistent with the BO syndrome. The patient's maternal grandfather and uncle were both hearing impaired; the uncle also had cysts over the sternocleidomastoid muscles. Shimasaki et al. (2004) suggested that the BO syndrome and Cayler syndrome may represent a spectrum of diseases.

Inheritance

Papadatos et al. (1974) favored multifactorial inheritance. Father and son were involved in some of their pedigrees. Miller and Hall (1977, 1979) observed this in a mother and her 2 sons by different fathers.

Cytogenetics

Rao et al. (1978) reported an infant with hypoplasia of the depressor anguli oris muscle and imperforate anus in association with a pericentric inversion of chromosome 15.

Deletion of 22q11.2 was observed by Giannotti et al. (1994) in cases fitting into the spectrum of Cayler syndrome, which they referred to as Cayler cardiofacial syndrome and considered to be part of the CATCH22 phenotype (see 188400). Rauch et al. (1998) described monozygotic twins who were concordant for 22q11.2 deletion and Cayler syndrome. Both had tetralogy of Fallot, as well as hypoplasia of the depressor anguli oris muscle, bifid uvula, and T-cell anomalies. These twins were diamniotic and dichorionic; a discordant phenotype with 22q11 deletion was reported in monozygotic, probably monochorionic, twins by Goodship et al. (1995) and by Fryer (1996). In monochorionic twins, discordant malformation may be related to the twinning process itself.

Shashi et al. (2003) considered Cayler cardiofacial syndrome, along with DiGeorge syndrome and velocardiofacial syndrome (192430) (Burn et al., 1993; Matsuoka et al. (1994, 1998)), to be a manifestation of the chromosome 22q11 deletion syndrome.