Congenital Heart Defects, Hamartomas Of Tongue, And Polysyndactyly

A number sign (#) is used with this entry because of evidence that congenital heart defects, hamartomas of tongue, and polysyndactyly is caused by compound heterozygous mutation in the WDPCP gene (613580) on chromosome 2p15. One such patient has been reported.

Clinical Features

Among the children of healthy, unrelated parents, Orstavik et al. (1992) observed a sister and brother with congenital heart defects, hamartomas of the tongue, and polydactyly. Both had coarctation of the aorta, which was repaired in early infancy. In addition, the girl had atrioventricular canal; she died postoperatively at age 4 years. The boy had fibrous subaortic stenosis and died of pneumonia at age 2 years. Both children had normal psychomotor development. The girl had total bony syndactyly between digits 3 and 4 of the right hand as well as an extra broad-based bony digit postaxially on both hands and a bifid right great toe. Three pea-sized polyps on the dorsum and left rim of the tongue, present from birth, were removed at the age of 1 year. When she was 1 year old, the parents had noted that the left leg was colder than the right. Although angiography showed no difference in blood supply of the legs, hypoplasia of the left lower limb became more obvious as she grew. The boy had a pedunculated postminimus on the left hand and 2 pea-sized polyps of the tongue. Orstavik et al. (1992) concluded that this might represent a previously unrecognized autosomal recessive syndrome or perhaps parental gonadal mosaicism for a dominant syndrome.

Digilio et al. (1996) reported a girl, the first child of healthy, nonconsanguineous parents with an unremarkable family history, who had congenital heart defects, hamartomas of the tongue, and polysyndactyly. She was born vaginally at term after an uncomplicated pregnancy. Birth parameters were normal. In the first month of life, she was found to have partial atrioventricular canal with a cleft of the mitral valve, and a common atrium with a septum between the pulmonary veins and the mitral valve (cor triatriatum type). Oral examination showed 3 polyps located on the dorsum and lateral rims of the tongue. These polyps were removed at 7 months of age and determined on histology to be hamartomas. She had postaxial polydactyly and cutaneous syndactyly of fingers 2 and 3 on the left hand and bilateral hallucal polysyndactyly. She also had an imperforate hymen. At 6 years of age facial appearance was mildly dysmorphic, with hypertelorism and retrognathia. Intellectual development was normal. X-ray examination showed a postaxial extra finger on the left hand and hexodactyly of both feet caused by hallucal duplication. The phalanges of the big toe were duplicated and deviated on the left, while only the distal phalanx was duplicated on the right. There were no additional skeletal anomalies. Ophthalmologic and audiometric evaluations were normal at age 6, as were cerebral, abdominal, and pelvic ultrasound examinations. Karyotype was 46,XX with no visible anomalies.

Saari et al. (2015) reported a girl, naturally conceived and the product of a 40-week singleton pregnancy, born to nonconsanguineous parents of mixed European ancestry. Birth parameters were normal. The patient was noted at birth to have type A postaxial polydactyly of both hands and broad halluces with 2/3 toe syndactyly. Radiographs revealed bilateral duplication of the fifth metacarpals with biphalangeal accessory digits and duplication of both halluces. Coarctation of the aorta was detected in the neonatal period and repaired surgically at 2 months of age. During infancy, the patient was found to have 2 growths on the right ventral surface of the tongue, causing feeding difficulty; these growths were resected at age 6 months and found to be lipomatous hamartomas. Pharyngeal and laryngeal anatomy, growth parameters, facial features, and motor and language development were normal. A diagnosis of CHDTHP was considered. Because mutation in a Bardet-Biedl syndrome (BBS; see 209900)-related gene was found, the patient was investigated for ocular, renal, and pelvic abnormalities; none of these was found (see MOLECULAR GENETICS).

Molecular Genetics

By whole-exome sequencing, Saari et al. (2015) detected compound heterozygosity for mutations in the WDPCP gene, a frameshift (613580.0004) and a missense mutation (613580.0005), in a patient with CHDTHP. Each parent was heterozygous for 1 mutation; 2 asymptomatic sibs were heterozygous for the frameshift mutation. Because the WDPCP gene is mutated in BBS, Saari et al. (2015) referred their patient for a screen for ocular abnormalities. At age 3 years there were no signs of retinal degeneration, symptoms of nyctalopia, or peripheral vision loss. However, BBS-related retinal dystrophy typically occurs later than age 3 years. Additionally, renal and pelvic ultrasound revealed no abnormalities.