Ruvalcaba Syndrome

Clinical Features

Ruvalcaba et al. (1971) described 2 brothers, born to unrelated parents, who showed mental retardation, short stature, microcephaly, peculiar facies with hooked nose and small mouth, narrow thoracic cage with pectus carinatum, hypoplastic genitalia, hypoplastic 'onion skin' cutaneous lesions, and skeletal deformities including short metatarsals and metacarpals and epiphysitis of the spine. Because 2 female maternal cousins showed some of the same features, X-linked semi-dominant inheritance was considered. One of the girls seems to have been fully affected, however. She died at age 17 years with congenital hydrocephalus and the Dandy-Walker anomaly.

Geormaneanu et al. (1978) reported a 7-year-old boy and his father with the syndrome and a possibly coincidental t(13q;14q) translocation.

Bianchi et al. (1984) described a single case in an Italian male.

Under the designation of Ruvalcaba syndrome, Sugio and Kajii (1984) described a kindred with 9 affected persons in 4 generations. They showed postnatal growth retardation, oval face with high forehead, antimongoloid slant of palpebral fissures (the kindred was Japanese), small, beaked nose with hypoplastic nasal alae, small downturned mouth with thin vermilion borders, pointed chin, and short digits. This kindred differed from that reported by Ruvalcaba et al. (1971) in the lack of mental retardation. Hunter (1985) disagreed with the diagnosis of Sugio and Kajii (1984) and considered the disorder to be different from Ruvalcaba syndrome. He pointed to the absence of mental retardation and microcephaly and the presence of sparse hair, beaked nose, long upper lip, and severe degree of metacarpal phalangeal shortness. Niikawa and Kamei (1986) proposed that this is a separate entity which should be called trichorhinophalangeal syndrome, type III (TRPS3; 190351).

Adachi et al. (2010) reported a Japanese girl with clinical manifestations identical to those reported by Ruvalcaba et al. (1971). Born of unrelated parents, she presented at age 6 months with failure to thrive, multiple congenital anomalies, and developmental delay. She had microcephaly, brachycephaly, small and downslanting palpebral fissures, beaked nose with hypoplastic nasal alae, and synophrys. Skeletal anomalies included very short stature, small hands and feet, talipes planus, talipes valgus, short IV and V metacarpals, pectus excavatum, scoliosis, an irregular spinal endplate, and restricted motion of the hip joints. She also had gastric volvulus and recurrent ear infections resulting in hearing impairment. She was severely mentally retarded and had limited breast development at age 13 years. The patient's mother had acetabular dysplasia and downslanting palpebral fissures. Molecular studies of the proband excluded mutation in the TRPS1 (604386) and GNAS1 (139320) genes, and 244K-CGH microarray analysis was negative. Adachi et al. (2010) concluded that Ruvalcaba syndrome is a distinct disease entity.