Limb/Pelvis-Hypoplasia/Aplasia syndrome (LPHAS) is a rare autosomal recessive disorder, characterized by a profound deficiency of the limbs, absent or hypoplastic pelvic bones, skull defects, thoracic dystrophy, unusual facies, and genital malformations. Pelvic bones show sacral agenesis or hypoplasia, whereas the skull might show a defect of the occipital bone with or without meningocele. Characteristic facial features include dysplastic and large ears, high and narrow palate, broad nasal bridge and nose, and a broad neck. Genital malformations include Mullerian aplasia, and agenesis of the uterus and vagina in females, and micropenis with cryptorchidism in males. Affected patients display normal growth and intelligence.
Al-Awadi et al. (1985) were the first to report a case of this condition. The patients they reported on were two siblings, born to healthy consanguineous parents from Jordan. The older patient, a 12-year old girl, presented with an elongated face, a right epicanthic fold, broad nasal bridge and nose, a broad neck, a barrel shaped chest with prominent sternum, lack of elbows with contraction deformity, short forearms, four digits in each hand, vestigial nails, and missing fifth ulnar ray with fusion of some of the carpal bones. She had gross pelvic malformation with very short appendages made up of one lower limb bone with a detached head and neck of femur. Her lower limbs were useless. Her 10-year old brother showed a similar phenotype. His external genitalia were anteverted, and he had inguinal testes a deep anal pit, and no gluteal cleft. Both patients had normal intelligence. Three other siblings were phenotypically normal. There was no other family history for such a condition. Later, Teebi (1993) further reported on the re-evaluation of the female patient. By this time, she was 18-years old, and had not attained menarche, although secondary sexual characters had developed. Her FSH, LH, and prolactin levels were found to be normal. Abdomenal ultrasonography revealed normal ovaries, but an absent uterus.
Farag et al. (1993) described a Bedouin girl, born to consanguineous parents belonging to a highly inbred tribe. The neonate had normal anthropometric measurements, except for a short length, which was due to profound limb hypoplasia and aplasia, especially of the lower limbs. The upper limbs showed contracture deformities, brachymesomelia, absent ulna, angulated radii, and postaxial oligodactyly. She had flask shaped thighs, phocomelia, and hypoplastic feet. The external genitalia were displaced anteriorly. X-ray studies showed short ulna, angulated radii, oligodactyly with absent rays in the upper limbs, and proximal hip dislocation, bifurcated femora, absent tibia and fibula and some rays in the lower limbs. Pelvic ultrasonography revealed an absent uterus, indicating Mullerian aplasia. The patient had a normal karyotype. The patient showed no developmental retardation at a later assessment.
Al-Naggar et al. (2004) described three Kuwaiti patients with LPHAS (two males, one female) from two families. The affected patients had intercalary and distal limb reduction malformations, hypoplastic pelvic bones, and unusual facies. Two of them showed capillary hemangiomata, sparse hair, short nose, dysplastic ears, and retrognathia. One of the patients had a balanced, reciprocal translocation, t(1,3)(q32:q21). The remaining two had normal karyotypes.
[Al-Naggar RL, Al-Awadi SA, Hanafi EM, Al-Adwani A, Al-Daboos RM, Abu-Alhassan SJ, Murthy K, Marafi MJ, Bastaki LA. Limb/pelvis hypoplasia/aplasia (Al-Awadi/RaasRothschild) syndrome in three new Kuwaiti patients: clinical and radiological description. Egypt J Med Hum Genet. 2004; 5(1):59-68.]
[See also: Jordan > Al-Awadi et al., 1985; Teebi, 1993].
Al-Qattan et al. (2009) reported a case of congenital duplication of the palm syndrome in a patient who also had a mutation in exon 4 of the WNT7A gene. Two years later, Eyaid et al. (2011) described three affected individuals (brother and sister and their female cousin) belonging to two related Saudi Arabian families. All three had a similar phenotype characterized by pelvic hypoplasia and truncated appendages replacing the lower limbs, but the upper limb phenotype ranged from absence of the ulna with a short radius and one missing digit per hand to a single bone with absence of elbow joint and only two digits per hand to total absence of the upper limbs (amelia).
Woods et al. (2006) have performed WNT7A mutational screening on three affected children in a consanguineous Syrian family living in the United Arab Emirates and suffering from absence of ulna and fibula with severe limb deficiency.
[See: Syria > Woods et al., 2006].