Cutis laxa is a rare connective tissue disorder characterized by a loosely hanging, wrinkled skin that lacks elasticity. This condition of the skin is marked in the face, giving a prematurely aged appearance. Additional features of the condition include thickening and darkening of the affected areas of the skin, hypermobility of the joints, skeletal abnormalities (hip dislocation, spinal curvature, and others), emphysema, hernias, diverticula in the bladder and esophagus, and in severe cases, impairment of internal organs. Autosomal recessive Cutis Laxa Type 2 (ARCL2) is the most severe form of this condition, and is characterized by an onset at birth. In ACRL2, the condition is extremely severe over the hands, feet, and abdomen. Other features seen include growth retardation, flat feet, delayed closure of the anterior fontanel, a typical facial appearance with down-slanting palpebral fissures, and bilateral congenital dislocation of hips are also common.
Autosomal recessive cutis laxa type IIA is associated with homozygous or compound heterozygous loss-of-function mutations in the ATP6V0A2 gene, which encodes the alpha-2 subunit of the V-type H+ ATPase.
Reisner et al. (1971) described two sisters with congenital cutis laxa associated with severe intrauterine growth retardation and congenital dislocation of the hip. The parents were first cousins. Reisner et al. (1971) suggested that the severe form may occur only or mainly in females because it is lethal to the male fetus. Two years later, Gazit et al. (1973) described the wrinkly skin syndrome in these two girls and their newborn brother, born to consanguineous Jews originating from Iraq. This report was written without the knowledge that these same two girls had been reported previously by Reisner et al. (1971) as one of the first examples of the syndrome of cutis laxa with growth and developmental delay.
Sakati et al. (1983) reported six cases, all female, and raised the question of X-linked dominant lethal in the hemizygous male. Three years later, Allanson et al. (1986) reported an affected girl with first-cousin parents of Saudi Arabian extraction.
[Sakati NO, Nyhan WL, Shear CS, Kattan H, Akhtar M, Bay C, Jones KL, Schackner L. Syndrome of cutis laxa, ligamentous laxity, and delayed development. Pediatrics 1983; 72: 850-6.]