Chitayat Syndrome

A number sign (#) is used with this entry because of evidence that Chitayat syndrome (CHYTS) is caused by heterozygous mutation in the ERF gene (611888) on chromosome 19q13.

Description

Chitayat syndrome is a rare condition characterized by respiratory distress presenting at birth, bilateral accessory phalanx resulting in shortened index fingers with ulnar deviation, hallux valgus, and characteristic facial features including prominent eyes, hypertelorism, depressed nasal bridge, full lips, and upturned nose (summary by Balasubramanian et al., 2017).

Clinical Features

Chitayat et al. (1993) reported a 5.5-month-old boy, born to nonconsanguineous French Canadian parents, who had diffuse bronchomalacia, facial dysmorphism, and digital anomalies. The proband had postdelivery respiratory distress requiring assisted ventilation for more than a week. CT scan of the chest showed marked narrowing of the first- and second-generation bronchi, and lung biopsy revealed that all of the small distal bronchi had absent or immature cartilage. Dysmorphic features included a box-shaped skull with frontal and parietal bossing, prominent eyes with hypertelorism, depressed nasal bridge, midface hypoplasia, long philtrum, full lips, and retrognathia. His hands were small with short middle fingers, and there was an extra bone on the radial aspect of the index fingers bilaterally. The index fingers also showed clinodactyly, and there was proximal insertion of the thumbs, soft tissue syndactyly of the thumb and index fingers, and overlapping of the index and fourth fingers of the middle finger. His feet showed bilateral hallux valgus. Skeletal survey revealed bilateral hyperphalangism involving 1 accessory phalanx on the radial aspect of the second digit on the left hand and 2 on the right, with partial syndactyly of the thumbs and second digits that included the extra phalanges. There was also bilateral dysplasia of the proximal phalanx of the third and fourth digits and of the second phalanx of the fifth finger, as well as delayed ossification of the carpal bones. In the feet, there was proximal displacement of the proximal phalanx and hallux valgus of both great toes. At 5.5 months of age, the infant had respiratory distress with tachypnea, pectus excavatum, and intercostal retractions, and continued to require oxygen supplementation.

Balasubramanian et al. (2017) provided follow-up on the patient originally described by Chitayat et al. (1993). The patient experienced respiratory difficulties secondary to bronchomalacia for the first 5 years of life, with recurrent severe respiratory infections and severe bronchospasm requiring admission to intensive care. His respiratory condition gradually improved, and at 21 years of age, he had obstructive pulmonary disease with an FEV(1)/FVC ratio of 52% (normal being greater than 80%). He showed no response to bronchodilators and had mild exertional dyspnea.

Tanaka et al. (1994) described a 5-month-old Japanese boy with features similar to those of the patient reported by Chitayat et al. (1993). The Japanese infant had tachypnea with retractions during the neonatal period, but his dyspnea gradually resolved by age 2 months. Digital anomalies in this patient included markedly hypoplastic middle phalanges of the second through fifth digits, and although he did not exhibit hyperphalangism, the proximal phalanges of the second digit were 'stubby.' In addition, he showed mesomelic upper limb shortness, and rhizomelic lower limb shortness.

Low et al. (2013) reported a mother and daughter with similar hand and foot deformities, pectus excavatum, recurrent respiratory infections, and, in the daughter, tracheomalacia. The proband exhibited bilateral hand anomalies comprising short broad thumbs, short deviated index fingers, and clinodactyly of the fifth fingers. Her feet showed broad valgus-deviated halluces as well as a laterally deviated second toe on the right. X-rays of the proband at age 5.25 years revealed a supernumerary bone in the index and middle fingers with severe delta phalanxes, clinodactyly of the fifth fingers, and a proximal delta phalanx of both great toes. The mother had previously undergone hand surgery, but x-rays showed duplication of the proximal phalanx of both thumbs. Her great toes had a deficient proximal phalanx lying medially and a complex enlarged distal phalanx which appeared to articulate with an interphalangeal joint and also with the metacarpophalangeal joint.

Balasubramanian et al. (2017) studied 5 patients from 4 families with Chitayat syndrome, including the patient originally described by Chitayat et al. (1993). All 5 patients appeared to have the same clinical phenotype, comprising accessory phalanges at the base of the index fingers resulting in ulnar deviation and shortened index fingers bilaterally, bilateral hallux valgus, and similar facial features, including prominent eyes with hypertelorism, depressed nasal bridge, short columella, high-arched eyebrows, upturned nose, and full lips. In addition, all of the patients presented with respiratory distress at birth requiring ventilatory support, and abnormalities of the respiratory system including bronchomalacia/tracheomalacia were complicated by recurrent severe respiratory infections. All 5 displayed pectus excavatum; other common features included hyperphalangism of the index and middle fingers and polyhydramnios.

Cytogenetics

Low et al. (2013) performed telomere studies and array CGH in an affected mother and daughter and identified a 227-kb duplication within 15q26.3 in both. The authors noted that duplication of this region was listed as a copy number variation in the Database of Genomic Variants, and suggested that the duplicated region might represent a benign copy number variant.

Molecular Genetics

In 5 patients from 4 families with Chitayat syndrome, including the patient originally described by Chitayat et al. (1993), Balasubramanian et al. (2017) identified heterozygosity for a recurrent missense mutation in the ERF gene (Y89C; 611888.0008). The mutation, which was present in an affected father and son in 1 of the families, was confirmed to have occurred de novo in the remaining 3 patients.