Cutis laxa is a multisystemic disorder charactarized by lax skin and wrinkles of variable severity, abnormal growth, developmental delay, and associated skeletal abnormalities. Cardiovascular, pulmonary and central nervous systems are often involved. The dermatological condition 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.
Cutis laxa can be easily diagnosed by a dermatologist, just by the external clinical signs. Unfortunately, there is no known treatment for the condition. Instead, management of the disease is targeted towards managing the impairment to internal organs. Patients can benefit, although only for a temporary period, from cosmetic surgery aiming at reducing the wrinkling of the skin. In the most severe cases, death occurs within the first few years of life.
Reversade et al. (2009) carried out mutation analysis for the PYCR1 gene in Bahraini patients affected with ARCL2 and detected the c535G>A mutation.
[See: Syria > Dimopoulou et al., 2013].
Nanda et al. (2008) reported three children from two unrelated consanguineous Kuwaiti families with congenital cutis laxa who displayed overlapping features of geroderma osteodysplastica and wrinkly skin syndrome. All three patients had dysmorphic facial features, wrinkled skin that was more marked on the hands and feet, hyperextensible joints, intrauterine growth retardation, developmental delay, congenital dislocation of hips, and osteoporosis.
Rajab et al. (2008) reported three sibs from a consanguineous Omani family with congenital cutis laxa, microcephaly, osteopenia, and mental retardation. Affected sibs had 'typical geroderma osteodysplastica features' including a 'droopy' face with deep-set eyes, maxillary hypoplasia, relative mandibular hypoplasia, bowing of the long bones, and frequent fractures due to osteopenia.
Al-Gazali et al. (2001) reported five children from two consanguineous families, of Palestinian and Syrian origin, respectively, with features overlapping both geroderma osteodysplastica and wrinkly skin syndrome. All five children had similar dysmorphic facial features, consisting of broad and prominent forehead, hypotelorism with epicanthal folds, prominent bulbous nose, flat malar region, and large protruding ears. All had wrinkling of the skin, more marked on the dorsum of the hands, feet, and abdomen; hyperextensibility of joints, particularly of the hands; and an aged appearance. Intrauterine growth retardation, subsequent failure to thrive, developmental delay, and a variable degree of osteoporosis were also present in all five. The three older children developed progressive prognathism. Al-Gazali et al. (2001) suggested that geroderma osteodysplastica and wrinkly skin syndrome represent variable manifestations of the same disorder.
Hamamy et al. (2005) described a 2-year-old girl, born of consanguineous Palestinian parents, with congenital wrinkly skin on the dorsa of the hands and feet and anterior abdominal wall, prominent veins on the chest, and hyperextensibility of the small joints of the hands and feet. She had a triangular senile-looking face with hypotelorism, a prominent bulbous nose, large protruding ears, and brachycephaly. MRI revealed agenesis of the corpus callosum with absence of the cingulate gyrus and sulcus, and a high third ventricle with colpocephaly. Hamamy et al. (2005) noted that corpus callosum agenesis was also reported in two sibs with wrinkly skin syndrome from a Syrian family described by Al-Gazali et al. (2001).
Reversade et al. (2009) performed homozygosity mapping in five consanguineous families segregating autosomal recessive cutis laxa, including a Palestinian family and one of the Kuwaiti families previously described by Hamamy et al. (2005) and Nanda et al. (2008), respectively. They identified a 2.8-Mb minimal candidate region on chromosome 17q25 between markers rs8065431 and rs1046896 containing 59 genes. Reversade et al. (2009) detected a c.617-633+6del23 PYCR1 gene mutation in a two-year-old Palestinian girl affected with ARCL2 disorder. The girl was born to first cousin parents.
Reversade et al. (2009) reported a c.616G>A PYCR1 gene mutation in a Qatari family with the ARCL2 disorder.
Reversade et al. (2009) sequenced the PYCR1 gene in two sibs with ARCL2 and detected the c.797+2-797+5delGTGG mutation.
Dimopoulou et al. (2013) described 33 patients with ARCL2, of which three were from Syria and one from Iraq. The Syrian patients were found to have homozygous splice site mutations at exon 4 of PYCR1 gene. The Iraqi patient had a homozygous p.Ala179Thr mutation at exon 4. The study focused on genotype/phenotype correlation and concluded that intra-uterine growth retardation, hypotonia, and psychomotor retardation, together with typical facial gestalt should allow for a successful differential diagnosis.
[See also: Palestine > Al-Gazali et al., 2001].
[See: Bahrain > Reversade et al., 2009; Qatar > Reversade et al., 2009].