Cutis Laxa, Autosomal Recessive, Type Iiib

A number sign (#) is used with this entry because this form of de Barsy syndrome (ARCL3B) is caused by homozygous or compound heterozygous mutation in the PYCR1 gene (179035) on chromosome 17q25.

Description

De Barsy syndrome, also known as autosomal recessive cutis laxa type III (ARCL3), is a rare autosomal recessive disorder characterized by an aged appearance with distinctive facial features, sparse hair, ophthalmologic abnormalities, intrauterine growth retardation (IUGR), and cutis laxa (summary by Lin et al., 2011).

For a phenotypic description and a discussion of genetic heterogeneity of de Barsy syndrome, see 219150.

For a phenotypic description and a discussion of genetic heterogeneity of autosomal recessive cutis laxa, see 219200.

Clinical Features

Lin et al. (2011) identified a patient with de Barsy syndrome from a nonconsanguineous Chinese family whose birth weight (2.4 kg) and length (42 cm) were both below the 3rd centile. At birth he had wide fontanels, prominent forehead, fine and sparse hair, splayed eyebrows, sunken eyes, small palpebral fissures, hypertelorism, pinched nose with hypoplastic nares, thin lips, and posteriorly rotated large helices. Skin was thin, wrinkled, and translucent, showing superficial veins. He had flexion contractures of upper limbs, flat feet, bilateral inguinal hernia, and undescended testes. Congenital glaucoma and blue sclerae were identified at 1 month of age. He had dislocation of hip joints and idiopathic hypertrophic pyloric stenosis. At 6 years of age he could speak only a few words. He had osteoporosis identified by 3 years of age and a dilated aortic root identified at 4 years. He sustained bilateral femoral neck fractures and had significant speech delay, athetoid movements, and moderate intellectual disability. Brain MRI was normal.

Molecular Genetics

In 2 families with clinical features of de Barsy syndrome, one of which was described by Kunze et al. (1985), Reversade et al. (2009) sequenced the PYCR1 gene and identified homozygosity for mutations in the PYCR1 gene (179035.0009, 179035.0010).

In a patient with de Barsy syndrome, Lin et al. (2011) identified compound heterozygosity for a frameshift and a missense mutation in the PYCR1 gene (179035.0011, 179035.0012).