Limb/pelvis-hypoplasia/aplasia syndrome (Al-Awadi/Raas-Rothschild syndrome): report of two Italian sibs and further confirmation of autosomal recessive inheritance.

Abstract

A third family with two Italian neonates affected with limb/pelvis-hypoplasia/aplasia syndrome is reported. The disorder shows autosomal recessive inheritance. (J Med Genet 1993;30:65-9) Limb/pelvis-hypoplasia/aplasia syndrome was defined by Raas-Rothschild et Radiographic examination (figs 2 and 3) showed a poorly ossified calvarium and pseudarthrosis of the right clavicle; traumatic fractured left humerus, shortened and bowed radii, absent ulnae, and hypoplasia/aplasia of the metcarpals and phalanges; underdeveloped iliac bones and absent pubic bones; aplastic femora, hypoplastic tibiae, absent fibulae, and hypoplasia/aplasia of the tarsals, metatarsals, and phalanges. Ultrasonographic examination showed no abnormalities of internal organs. The infant died aged 16 days of respiratory distress. No necropsy was performed. CASE 2Case 2, a female, was the sister of case 1. Inexplicably, no fetal ultrasonography was performed before 30 weeks of gestation. At this time it showed a fetus with normal humeri, shortened and bowed radii, absent ulnae, and dysplastic, short lower limbs. The infant was delivered at 39 weeks by caesarian section. Birth weight was 3300 g (50th centile), birth length 41 cm (<3rd centile), head circumference 32-5 cm (3rd centile), and chest circumference 35 cm (90th centile). She showed a similar phenotype to case 1 (fig 4). Ultrasonographic examination indicated no abnormalities of the internal organs. X ray examination (figs 5 and 6) showed a poorly ossified skull, pseudarthosis of the right clavicle, bowed radii, absence of the ulnae, hypoplastic pelvic bones, hypoplastic femora, slender tibiae, absent fibulae, and hypoplasia/ aplasia of the metacarpals, tarsals, metatarsals, and phalanges. The spine was considered to be normal.The clinical and radiological findings in our patients, compared with those cases described by Al-Awadi et aP and by Raas-Rothschild et all are reported in tables 1 and 2. Discussion

A newly recognized syndrome involving limbs, pelvis, and genital organs or a variant of Al‐Awadi/Raas‐Rothschild syndrome?

“…AARRS is an autosomal recessive disorder, which is characterized by the presence of profound limb and pelvic deficiency, thoracic dystrophy, and genital anomalies. Limb anomalies consist of short and bowed radii, aplasia of ulna and fibula, hypoplastic or aplastic femur, hypoplasia/aplasia of tarsals, carpals, metatarsals, metacarpals, and phalanges [Al-Awadi et al, 1985;Richieri-Costa, 1987;Raas-Rothschild et al, 1988;Camera et al, 1993;Kumar et al, 1997]. The findings found in our patient appear similar to those of AARRS.…”

“…Regarding hand anomalies, severity of the hand anomalies in the present patient appears to be very mild compared to those of most cases of AARRS. Hypoplastic nail which is common in AARRS was not present in our patient [Al-Awadi et al, 1985;Camera et al, 1993;Farag et al, 1993]. We are not convinced that unusual facies are component of the AARRS as they were not remarkable in the previously reported cases.…”

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

“…Similar patients have also had acrania [Schinzel, 1990;Chitayat et al, 1993], renal agenesis, meningocele, hypoplasia of the cerebellum [Camera et al, 1993] and abnormal development of the Mü llerian system [Farag et al, 1993]. Phenotypic similarity, ethnic origin, and autosomal recessive inheritance suggest the existence of one or several similar entities the FFU complex, and the Fuhrmann, Al-Awadi, Raas-Rothschild, and Schinzel phocomelia syndromes.…”

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

“…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.…”

“…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.…”