Multiple Pterygium Syndrome (MPS) is a rare congenital multiple-anomaly disorder characterized by webbing of the neck, elbows, knees, armpits, and fingers, multiple joint contractures, vertebral defects, growth retardation, several musculoskeletal abnormalities, and minor facial defects. Various cardiovascular, respiratory, gastrointestinal, and genitourinary system abnormalities may also be seen in association with these characteristic findings. The Escobar variant of MPS a non-lethal form of the condition, is an autosomal recessive form of distal arthrogryposis characterized by arthrogryposis multiplex congenita, typical facial appearance, ophthalmologic anomalies, atrophic calf muscles, and interdigital, neck, and axillary pterygia. Other features also include furrowed tongue and enlarged corneal nerves.
It is important to differentiate this condition from the Popliteal Pterygium Syndrome (PPC) and Arthrogyposis Multiplex Congenita (AMC). This can be easily done based on the joint contractures in PPS being limited to the knee, and by the progressive nature of the Escobar Syndrome as compared to AMC.
Naguib et al. (1987) described an Arab family in which the parents are first cousins and with five siblings having multiple pterygium syndrome. The last pregnancy which produced an affected sib was prenatally diagnosed by ultrasonography.
In 1990, Teebi and Daoud ascertained the presence of 13 cases (five males and eight females) of MPS in six sibships in four Arab families while reviewing the data of a community genetic survey at Farwania district hospital, serving a mixed Arab population of 400,000. Their ages ranged from soon after birth to 19 years. In one family, parents were normal, first cousin Kuwaiti Bedouin with five affected children (two females and three males), who have been reported by Naguib et al. (1987). The family also had six normal children (two males and four females). At the time of the study, the oldest normal daughter married to a non-consanguineous Bedouin and has had an affected girl with multiple contractures and pterygia noted at birth. Teebi and Daoud (1990) indicated that the manifestations in this family are typical of autosomal recessive MPS with marked intrafamilial variability. In a second family, the parents were normal, first cousin Kuwaitis whose first child (female) had congenital joint contractures, pterygia, and the typical facial appearance, as noted at the age of 7 months. Teebi and Daoud (1990) estimated the minimum prevalence of MPS in the general population of Farwania district as approximately 1 in 31,000 indicating the relatively high occurrence of this disease in Arab populations [See also: Palestine > Teebi and Daoud, 1990].
A survey performed by Bastaki et al. (1992) between 1985 and 1989 reported the overall incidence of genodermatosis in Kuwait Maternity Hospital to be 0.26 per 1000 livebirths. More specifically, the incidence of multiple pterygium was 0.05 per 1000 livebirths in Kuwait during the over-mentioned period of five years.
Sawardekar (2005) conducted a study to establish the prevalence of major congenital malformations in children born during a 10-year period in Nizwa Hospital. Of the 21,988 total births in the hospital, one child was born with the Escobar Variant of Multiple Pterygium syndrome. Sawardekar (2005) hinted for a possible genetic contribution in this child.
Rajab et al. (2005) reported six Omani children from two consanguineous families from the same tribe, with a multiple congenital anomaly syndrome defined by arthrogryposis multiplex congenita, typical facial appearance, ophthalmologic anomalies, atrophic calf muscles, and interdigital, neck and axillar pterygia. In the first family, five children of healthy first cousins were affected (one died at the neonatal period from unknown reason) and four were unaffected. The mother noticed reduced fetal movement in the pregnancies of the affected children. The first patient was a female who was born by normal delivery and was noticed to have joints contractures, left talypes equinovarus, and congenital dislocation of both hips. She had foot operations at the age of two and three years. Her motor development was delayed (walked at four years), but she had normal cognitive development. At the age of 14 years, she was friendly, with no hearing deficit, and with appropriate-for-age pubertal development. She was short (height below third centile), with flexed stance, waddling gait and spinal deformity. Her speech was dysarthric but comprehensive, with hypernasal voice. She had a pear shaped head, elongated face, a ridged metopic suture, low set ears, high arched eyebrows, right upper lid ptosis, relative left proptosis, hypoplastic maxilla, receding chin, a small pursed mouth which could not be opened wide to reveal a high arched palate, dental malocclusion, absent second and third molars with hypertrophic gums, and the tongue had a furrowed appearance with central spoon-like groove and appeared long and thin on protrusion. Her neck was short and webbed with low and wide posterior hairline. As regarding the joints, the right shoulder and hip were elevated, hands were flexed with ulnar deviation at the wrists, the knees, hips, ankles and all toes had flexion contractures, with right club foot deformity, left calcinovalgus deformity of plantar-flexed and rotated feet. The spine was malaligned with lumbar lordosis and kyphoscoliosis. Mild webbing of axilla and interdigital webbing crossing all interphalangeal joints were found but had no antecubital or popliteal webbing. The hands had hypoplastic dermal ridges and palmar creases with severe camptodactyly and absent thumb abduction and extension (due to congenital webbing and contracture of the thumb into the palm). Neurological examination revealed normal muscle power and deep tendon reflexes, but reduced peripheral muscle bulk. Her vision was compromised with hypermetropic astigmatism, and ophthalmologic examination revealed lagophthalmous (incomplete closure of palpebral fissure), euryblepharon, and prominent corneal nerves with absent corneal sensations. Her brother was also noticed to have talypes equinovarus and stiffness of multiple joints after uneventful pregnancy and birth. His motor development was delayed (walked at three years). Surgical procedures for feet deformities, heel cord lengthening, knee tendon release to improve knee flexion, right inguinal hernia and cryptorchidism were done for him. At the age of 12 years, he was short, thin, with a crouched stance and decreased peripheral limb muscle mass. His facial features and hand deformity were similar to his sister (case 1) but to a lesser degree. His gait was wide-based and walked with flexed hips and knees (flexion limited to 30 degrees) along with contractures at the elbows, knees, hips and both feet (fibulary deviated). He had mild thoracic scoliosis and mild muscular axillary webbing. Neurological examination was unremarkable with normal muscle power. Despite being mildly dysarthric, his school progress was excellent. The third sibling (10 years old) had similar facial features to the above patients, with slight asymmetry of eye size with left ptosis and mild right proptosis with a convergent squint. Tortuous retinal vessels and an abnormal pattern of vascularization of the optic nerve were seen on her retina. She was thin with hypoplastic peripheral muscle, joint contractures (less severe as she had physiotherapy since she was few months old), right talypes equinovarus, claw hand, camptodactyly and surgical scars on both feet. The last affected sibling in this family (eight years old) had the same facial features, along with flexed posture and mild ankylosis of the shoulder, wrists, elbows, hips, knees, ankles and feet, and mild thoracic scoliosis. The second family of healthy consanguineous parents had two affected children. The first of these was born with short neck, clenched fists, flexed hips, and knees fixed in extension and scoliosis. She was diagnosed with severe gastro-esophageal reflux which caused several episodes of aspiration pneumonia and failure to thrive. She died at the age of three months from pneumonia and sepsis. Her sibling was a newborn who presented with hypertelorism, low set ears, grooved tongue, clenched fists, camptodactyly, short neck with pterygia, flexed hips, extended knees and rocker-bottom deformity of the feet. As regarding the growth pattern, all of the patients had their average birth weights being 0.3 kg below the weights of unaffected siblings, while the OFC and length were similar. Their linear growth in the first year was slow, with their heights increasing steadily parallel to the third percentile. This was followed by deterioration of growth velocity which coincided with the development of scoliosis. Radiological examination revealed generalized osteopenia, and coarse trabeculation of the bone, osteopenic vertebral bodies of normal height, scoliosis, sacralization of L5, broad ribs, broad short femoral necks, broad ischii, thin midshafts of the long bones, and an upward dislocated patella. Hand anomalies seen on X-rays included finger flexion deformities with fibrous fusions of metacarpophalangeal (MCP) joints, widened shafts of the metacarpal bones, distal tapering of phalanges and dislocated thumb at the MCP joint. Mild brachycephaly and a steep anterior base of the skull, as well as dislocation of the hip, deformed femoral head and severe scoliosis were seen in patient one. Both babies in the second family had dislocated hips and genu recurvata. Laboratory investigations in all patients revealed normal karyotype and normal levels of hormones (thyroid, parathyroid, growth, and cortisol hormones), normal glucose, creatinine phosphokinase, serum calcium, lipid profile, liver and renal functions. Motor and sensory nerve conduction and EMG were normal, and so was the calf muscle biopsy from patients two, three, and five. Linkage to 2 known arthrogryposis loci, TPM2 on 9p13 and TNNI2 and TNNT3 on 11p15, was excluded. Rajab et al. (2005) concluded that these patients had numerous features of Escobar syndrome (ES), as well as some features of Freeman-Sheldon syndrome and arthrogryposis with ophthalmologic abnormalities. Later, Hoffmann et al. (2006) performed genome-wide linkage analysis on the second family of Rajab et al. (1995), and were able to detect homozygous mutations in the CHRNG (Cholinergic Receptor Nicotinic Gamma Polypeptide) gene on chromosome 2 in affected individuals.
In 1990, Teebi and Daoud reviewed the data of a community genetic survey at Farwania district hospital in Kuwait. They described two Palestinian families with MPS. The first family consisted of normal first cousin parents who had two affected children with MPS but without ptosis, a 19 year old male and a 10 year old female, and five normal children (two males and three females). A male child died in the neonatal period because of congenital heart disease. In a second Palestinian family of black African ancestors, two normal sisters were married to their normal first cousins who were brothers. One of the couples had three affected daughters. The oldest was 16 years old; she had severe respiratory impairment and later developed pulmonary hypertension and heart failure. There were five normal children with families (four males and one female). The other couple had an affected boy and another, recently born, affected girl in addition to two normal girls. Apart from the oldest girl, the children in this family had plastic surgery for their joints and webs in early life [See also: Kuwait > Teebi and Daoud, 1990].
Morgan et al. (2006) described a large consanguineous Saudi Arabian family with both lethal and the non-lethal (Escobar) variants of multiple pterygium syndrome. This family has five affected individuals (all males) as well as two affected individuals who died in the neonatal period. The proband had pterygia of the elbows, axilla, poplitea, thumb, and neck and facial dysmorphism (ptosis, downslanting palpebral fissures, and expressionless face) and rocker-bottom feet. In addition, he has some fused thoracic vertebra, a large eventration of the right diaphragm, and normal intelligence. His sister died at age 3 months because of congenital heart disease, and his brother died at age 3 days because of lung hypoplasia. The four living affected cousins were reported to have pterygia similar to that of the proband. At the molecular level, all the affected individuals with both variants were found to be homozygous for the missense Val107Gly mutation in the CHRNG gene.
Morgan et al. (2006) reported the presence of non-lethal Escobar variant of multiple pterygium syndrome in a UAE family of Pakistani origin.