Cleft Lip/palate With Abnormal Thumbs And Microcephaly

Juberg and Hayward (1969) described a syndrome with oral, cranial and digital manifestations in 5 of 6 children of normal, unrelated parents. Two brothers had cleft lip and palate, microcephaly, hypoplasia and distal placement of the thumbs, and elbow deformities limiting extension. One of the brothers had toe anomalies, as did 3 of the 4 sisters. Among the sisters microcephaly, stiff thumbs and forme fruste cleft lip were observed. Kingston et al. (1982) described a single case. In addition to unilateral cleft lip and palate, the 17-year-old boy had bilateral absent thumbs, anomalous carpal bones, deformity of the radial heads, and short stature (143.3 cm). He was found to have growth hormone deficiency. The sella turcica was normal by x-ray. Nevin et al. (1981) reported a case in a female who had absence of the pituitary fossa but no evident endocrine dysfunction to account for short stature. Verloes et al. (1992) described 3 nonfamilial cases of orocraniodigital syndrome. The main features were cleft lip/palate, hypertelorism, bowed and upward slanting eyebrows, thumb hypo/aplasia or proximal/distal thumb displacement, luxation of the radial head, elbow restriction, minor vertebral and rib anomalies and horseshoe kidneys. New features observed by Verloes et al. (1992) were mental retardation (not correlated with the severity of malformations), anterior anal displacement, and ptosis. Verloes et al. (1992) thought that recessive inheritance was likely but that autosomal dominant inheritance could not be totally excluded, making it wise to exercise caution in the genetic counseling of the parents of an affected child and of affected patients themselves.

Silengo and Tornetta (2000) reported a 10-year-old male with Juberg-Hayward syndrome. He had a cleft palate, distally placed thumbs, and multiple cervical hemivertebrae, but did not have a cleft lip. The parents were unrelated, and there was advanced parental age of 42. The mode of inheritance was unclear.

Reardon et al. (2001) reported a 9-year-old boy whose clinical presentation resembled Malpuech syndrome (248340), but who had radiologic features similar to those seen in patients with Juberg-Hayward syndrome. Clinical features in this patient consistent with both syndromes included short stature, hypertelorism, and cleft lip/palate; but he also had renal agenesis, umbilical hernia, and shawl scrotum, which had not been reported in Juberg-Hayward syndrome but had been seen in Malpuech syndrome. Radiologic features consistent with Juberg-Hayward syndrome included mesomelic shortening, elbow dislocation, carpal bone abnormalities, mild scoliosis, and vertebral endplate irregularity. Reardon et al. (2001) suggested that the Malpuech and Juberg-Hayward syndromes may be allelic.

Hedera and Innis (2003) reported a 14-year-old male with absent thumbs, bilateral cleft lip/palate, and microcephaly, severe mental retardation, severe skeletal abnormalities, as well as a facial appearance supporting the diagnosis of Juberg-Hayward syndrome. New findings in this patient included Dandy-Walker abnormality, hypospadias, and oral abnormalities, expanding the clinical spectrum of this syndrome. Hedera and Innis (2003) suggested possible overlap with orofaciodigital (see 258850) and Malpuech (248340) syndromes.