Twelve girls were diagnosed as symptomatic (manifesting) carriers. Although Duchenne muscular dystrophy is much more common in boys but girls have been described as having the disease in mild form. One of the Gower’s female patients was apparently a “manifesting carrier”18,19 With characteristic phenotypical features, majority of our patients especially those who have a clear history of one or more affected males in the family, most probably are manifesting carriers. This canbe explained onthe basis of Lyon’s hypothesis which suggests that in the affected girls most of the muscle cells-X-chromosomes, inherited from mother are active and lead to the manifestations of the disease20,21. Those females can also have DMD who have a translocation of the short arm of the X-chromosome with one of the other chromosomes. Boyd et al22 reviewed 20 girls with X- autosome translocation with breakpoints at Xp21 associated with Duchenne or Becker muscular dystrophy. Turner syndrome with an XO pattern is another rare situation which may co-exist with DMD in a girl, since the abnormal X is not suppressed by the missing normal chmmosome. In our patient who had chromosomal analysis, results were normal 46XX. Some other X-linked recessive disorders can also manifest in females with normal karyotype by inactivation of paternal X-chromosome or lyonization, as in cases of female patients of haemophilia23 or vasopressin-resistant diabetes insipidus24. Moser and Emery2, reported a large series of manifesting carriers with age varying from 4 to 79 years.
While others25 reported seven patients who presented during second and third decades of life with slowly progressive weakness. All had raised serum CK, myopathic EMGs and myopathic muscle biopsy. Sewry et al26 described three manifesting carriers aged 3,5 and 12 years and a presumptive carrier, 24 years old motherof 5 years old child. All had mosaic pattern on immunohistochemical staining. In our series patients are generally young and severely affected. The clinical course, rapidity of progression and severity of clinical manifestations can be similar both in boys and girls with DMD27. Two of our patients (No. 11,12) are sisters though not twins, with two affected brothers and a carrier mother with raised serum CK. There are several reports of monozygotic twin girls where one of the twin is a manifesting carrier and the other twin is normal heterozygous for DMD28-30. In one of the twins the mother was a non- manifesting carrier28. In four of our patients2,3,7,10. there was no family history, though phenotype was identical to DMD. Yainamoto eta! reported a two years symptomatic carrier of DMD confirmed by dystrophin studies an! there was no family history. Moser and Emery2 suggested that manifesting carriers of DMD are as common as limb girdle muscular dystrophy (LGMD), atleast in adults. There is considerable clinical overlap between LOMID and dystrophinopathies. In the past, DMD patients were diagnosed as LGMD. In one series,7 patients out of 41 and in other 13 patients out of 46 LGMI) were rediagnosed alter dystrophin studies as dystrophinopathies including DMD, BMD and manifesting carriers32,33. In LGMD onset is usually late and CK is either normal or slightly raised. This diagnosis was not considered in our patients. However, in two patients9,10, other diagnoses such as autosomal- recessive Duchenne-like muscular dystrophy and congenital muscular dystrophy (CMD) were considered. Autosomal recessive Duchenne-like muscular dystrophy has been reported from Africa34, Middle East35 and some other countries36. This condition differs slightly from X-linked DMD and has a milder course, affects deltoid muscles more severely, intelligence and ECG are normal and muscle biopsy has a more local pattern of muscle pathology37. It affects both boys and girls equally and sytrophin is normal38 Characteristic features of CMD include fixed deformities such as arthrogryposis, swallowing and respiratory difficulties or mental retardation. None of the rtient in this series had any of these features. Matsuniura et al reported occunence of CMD (Fukuyama type) and DMD in a Japanese family.
In our patients ECGs were not done, however, several investigators have reported ECG abnormalities inupto 90% of cases of DMD40,41. Commonly described abnormalities are sinus tachycardia, abnormally tall R waves and shallow S waves in the leads Vi and V2 and deep, narrow (non-infarction) Q waves in the lateral chest leads, short P-R interval, Rsr’ pattern in VI and bundle branch block. Emery42 and Russelet al43 have shown that amplitude sum (R-S)in lead VI is significantly greater in carriers than controls and RJS ratios in Vi and V2 are abnormal in carriers. There was no co-relation between CK levels and ECG findings43. Until recently, serum CK was the most commonly used screening method to detect DMD carriers. Similarly manual muscle testing has been used to detect the female carriers. By standardised manual muscle testing techniques, weak proximal muscles can be demonstrated in most carriers and some degree of proximal muscle weakness has been reported in majority of carriers44. With the availability of molecular genetics such as DNA analysis, polymerase chain reaction (PCR) techniques and dystrophin assays either by Western blot or immuno-histochemical studies, have revolutionized the ability to make accurate diagnosis of DMD/BMD, manifesting and non-manifesting carriers. However, at present these highly sensitive and accurate diagnostic facilities (to my knowledge) are not available in this country. Therefore, we shall have to rely on clinical manifestations, family history and laboratory data such as serum CK, EMG and muscle biopsy. Presence of X-linked inheritence in the family and raised serum CK in mother can be of great help in the diagnosis of Duchenne and Becker muscular dystrophy in females.
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