Pathological features and prenatal diagnosis in the newly recognised limb/pelvis-hypoplasia/aplasia syndrome.

Abstract

SUMMARY A second family with the autosomal recessive disorder now referred to as the limb/pelvis-hypoplasia/aplasia syndrome is reported. It is speculated that the gene for this rare skeletal dysplasia may be confined to the Middle East gene pool. The disorder has been shown to be diagnosable prenatally in a pregnancy at risk by using ultrasonography.In 1985, Al-Awadi et all first briefly reported on two Arab sibs of consanguineous parents with a newly recognised skeletal dysplasia disorder, consisting of profound limb deficiency, thoracic dystrophy, unusual facies, and normal intelligence.The purpose of this report is to describe and to discuss in detail a second affected consanguineous family with three affected offspring (the proband *and the two aborted fetuses) with this disorder, which we now call the limb/pelvis-hypoplasia/aplasia syndrome. Our reasons for renaming this condition will be discussed. Case reportsThe proband (fig 1) three abnormally shaped digits on each hand. The lower extremities showed severe phocomelic changes with absence of the feet. The external genitalia were displaced upwards. The penis appeared normal, but the scrotum was hypoplastic with bilateral cryptorchidism (fig 2). No other physical findings were noted. No definite diagnosis was made at that time but the parents were advised that, because of their consanguinity, they might be at risk for having similarly affected children. Furthermore, because of the severity of the malformations, it was suggested that all future pregnancies should be monitored by means of ultrasound, as there was a good chance At approximately one year of age, the proband was placed in a hospital for crippled children (Alyn Hospital, Jerusalem) and this is where he currently resides. He is at present four and a half years old, his weight is 11*5 kg (<3rd centile), and he has a head circumference of 49 cm (>2nd centile). Physical examination at this time showed a boy with normal facies except for a pointed chin and long ears. His state of alertness and intelligence appeared to be normal for his age.The upper limbs were short and symmetrically involved. Both elbow joints showed a flexion contracture deformity. His forearms were shortened and the wrist joints were very mobile. There was bilateral ectrodactyly of the hands, each having two fingers and a thumb, and all digits were malformed. The pelvis was grossly deformed. As commented upon previously, the external genitalia were displaced upwards and the scrotum appeared hypoplastic. Both testes were in the inguinal canal despite the fact that at three years of age he had had orchidopexy. Dermatoglyphic findings showed marked distortion of the digital and palmar prints, since only three digits were present on both hands. The left palm had only an axial triradius and one palmar crease was present. On the right palm there was one common triradius for digits II and III. No other triradii were present. On both palms there were many fine, small creases with no specific shape or direction. The left hand had a wh...

Familial aplasia/hypoplasia of pelvis, femur, fibula, and ulna with abnormal digits in an inbred Pakistani Muslim family: A possible new autosomal recessive disorder with overlapping manifestations of the syndromes of Fuhrmann, Al-Awadi, and Raas-Rothschild

“…A subsequent case report [Fuhrmann et al, 1980] described an association of poly-, syn-, and oligodactyly with aplasia and hypoplasia of femur and fibula, but without developmental abnormalities of the ulna and ulnar rays. Familial occurrence of similar combinations of developmental skeletal abnormalities was described with thoracic ''dystrophy'' (the Al-Awadi syndrome) [AlAwadi et al, 1985], and pelvis hypoplasia (the RaasRothschild syndrome) [Raas-Rothschild et al, 1988].…”

Consanguinity and Dysmorphology in Arabs

“…This syndrome has originally been reported in a nonBedouin Palestinian family from Kuwait [83] , followed by a more complete report on a second Arab family [84] .…”

Limb/pelvis hypoplasia/aplasia with skull defect (Schinzel phocomelia): Distinctive features and prenatal detection

“…However, in their coordinate analysis, Kosaki et al reported a quantitative ®nding of particular relevance to the comparison of Schinzel phocomelia and Al-Awadi/Raas-Rothschild syndrome. The children described by Schinzel, Al-Awadi, and Raas-Rothschild all clustered in a phenotypic``zone'' that was also distinct from other phocomelic conditions, supporting the hypothesis by Lurie and Wulfsberg [1993] that all of these authors were describing the same condition [Al-Awadi et al, 1985;Raas-Rothschild et al, 1988;Schinzel, 1990]. Genuardi et al [1997] reported on an infant with limb-pelvis hypoplasia, but without evident skull defects, who had bilateral femoral and ®bular aplasia with normal long bones of the upper extremities.…”

“…Autosomal recessive inheritance has been proposed for Schinzel phocomelia syndrome, because some families (Table II) have included two affected sibs born to healthy parents, and there is one instance of parents who were ®rst cousins [Schinzel, 1990;Chitayat et al, 1993;Evliyaoglu et al, 1996]. Consanguinity has also been documented in most case reports of sibs with AlAwadi/Raas-Rothschild syndrome [Al-Awadi et al, 1985;Richieri-Costa, 1987;Raas-Rothschild et al, 1988;Camera et al, 1993;Farag et al, 1993;Teebi, 1993;Mollica et al, 1995;Genuardi et al, 1997]. However, the molecular basis of these disorders has not yet been explored.…”

“…A skull ossi®cation defect was observed in a fetal ultrasound scan at 17 weeks' gestation in the report by *Al-Awadi/Raas-Rothschild (A-A/R-R) syndrome: 11 reports of limb/pelvis-hypoplasia/aplasia by Al-Awadi et al [1985], Raas-Rothschild et al [1988], Richieri-Costa [1987], Teebi [1993], Camera et al [1993], Farag et al [1993], Mollica et al [1995], and Genuardi et al [1997]. a , Present; Ð, not present; ?, ®nding not reported or determined.…”