MURCS association--a review of 7 cases.P Mahajan, A Kher, A Khungar, M Bhat, M Sanklecha, BA Bharucha
Dept of Paediatrics, Seth GS Medical College, Parel, Bombay, Maharashtra.,
MURCS association (Mullerian hypoplasia/aplasia, renal agenesis and cervicothoracic somite dysplasia) is emerging as the second most frequent cause of primary amenorrhoea after Turner syndrome. Seven cases have been described and analysed. All cases had absence of uterus and tubes 85% had cervical spine abnormalities such as vertebral fusion, hypoplasia of vertebrae or butterfly vertebrae and short stature and 28% had renal agenesis or ectopy. The latter finding is in contrast to the reports in world literature where the frequency of renal agenesis is higher. There was no familial incidence in these seven cases lending credence to the belief that the association is essentially sporadic.
Keywords: Abnormalities, Multiple, Adolescent, Adult, Case Report, Fallopian Tubes, abnormalities,Female, Human, India, Kidney, abnormalities,Mullerian Ducts, abnormalities,Spine, abnormalities,Syndrome, Uterus, abnormalities,
The realisation that Mullerian aplasia or hypoplasia sometimes occurs in association with a specific constellation of other congenital abnormalities, led to the description of the MURCS association (Mullerian hypoplasia/aplasia, renal agenesis and cervicothoracic somite dysplasia). This is a series of 7 cases, 1 including the one first described in India by Vaidya et al. It needs to be stressed that a more detailed evaluation is necessary in cases of primary amenorrhoed with Mullerian agnesis to establish that the patient has the MURCS association, and not simply Rokitansky Kuster Hauser syndrome. This has important ramifications for genetic counselling because Mullerian duct agenesis has been estimated to be the second most frequent cause of primary amenorrhoea after Turner syndrome.
This is theonly series to be described from India.
Cases of primary amenorrhoea were referred to the Genetic Clinic primarily for Karyotyping. Height and weight was recorded with percentiles, followed by a detailed clinical evaluation to rule out the Turner phenotype. Gynaecological evaluation (per rectal and/or vaginal palpation) for determining the presence of the uterus and fornicial structures was carried out. Puberty staging was done using Tanner's sex maturity rating.
Cervical and dorsolumbar spine X-rays and ultrasound examination for urogenital abnormalities was performed. Intravenous pyelography was performed in some cases Mullerian duct absence or hypoplasia was confirmed by laparoscopy.
Sex chromatin and/or karyotyping confirmed the genetic sex. All the cases had normal secondary sexual development.
The findings in the 7 cases are shown in [Table - 1].
The incidence of malformations observed in our series are compared with those reported in literature [Table - 2].
The Rokitansky Kuster Hauser syndrome which is characterised by developmental failure of the Mullerian duct structures often occurs with urinary tract abnormalities (36%) and skeletal abnormalities, (10-20%). Duncan et al in 1979, in a review of 30 cases proposed the designation of the entity consisting of anomalies of all 3 systems as “MURCS Association”.
The four most common malformations specifically described in the association are: 1. uterine hypoplasia or aplasia, 2. renal agenesis or ectopy, 3. vertebral anomalies and 4. adult stature less than 152 cms.
Our approach to all the cases with uterine aplasia/hypoplasia was to specifically look for renal and cervical spine abnormalities. Other minor abnormalities occasionally detected but absent in our cases include upper limb defects, rib abnormalities, Sprengel's shoulder, deafness, external ear defects, facial asymmetry, cleft lip and palate, micrognathia and GI abnormalities.
It is noteworthy that renal abnormalities, an integral part of this association was present in only 28% in our series as compared to 88% mentioned in literature.
The MURCS association should be differentiated from the following conditions which resemble it partially viz. 1. VATER association; 2. Rokitansky anomalad; 3. Turner syndrome; 4. Klippel-Feil anomalad More Details and 5. testicular feminisation syndrome.
The pathogenesis of this association is not clear. At the end of the fourth week of fetal life, the blastemas of the lower cervical-upper thoracic somite arm buds and pronephric buds are in close proximity to one another. The MURCS association could be produced at that time by a teratogenic event, which would affect the relations within these blastemas. Support for this concept is provided by the case of a patient exposed to thalidomide at the fetal age of 27-29 days. Heidenreich et al reported 2 cases of monozygotic twins in which only one had Rokitansky Kuster Hauser syndrome suggesting an environmental origin for that defect.
Although most cases appear to be sporadic there are reports of families in which siblings displayed utero-vaginal abnormalities of the MURCS association,. Such a finding was not seen in our series.
Thus, in some cases MURCS association may be a genetically determined pleiotropic condition in which affected relatives show a spectrum of abnormalities. Therefore, the MURCS association may be described as a polytopic field defect of multiple possible etiologies.
The prognosis of each case varies and is probably dependent on the extent and severity of renal abnormalities. The only autopsy report on a patient with MURCS association by Greene Robert et al revealed associated central nervous system, vascular and pulmonary abnormalities, probably indicating a multisystem involvement.
[Figure - 1][Table - 1], [Table - 2]