OBSTET-L Mensagens pela Fevereiro, 2002: Re: Enfermidade de Madlung X Gestação

Re: Enfermidade de Madlung X Gestação

From: Anabel Scaranelo

anabelms@uol.com.br

Mon, 18 Feb 2002 14:02:24 -0600 (CST)

The characteristics are typical deformity of the distal radius and ulna and proximal carpal bones and mesomelic dwarfism. The wrist deformity is often referred to as Madelung deformity. Langer (1965) reported 3 families. A striking preponderance of affected females made it important to observe male-to-male transmission before autosomal transmission is completely accepted. It was my impression that females are more severely affected than males. Hence, the preponderance of affected females may be the result of bias of ascertainment. The deformity of the forearm consists of bowing of the radius and dorsal dislocation of the distal ulna. Motion is limited at the elbow and wrist. Lamy and Bienenfeld (1954) described affected mother and son. The fibula was absent in both. Reviewing cases of Madelung deformity, Felman and Kirkpatrick (1969) concluded that patients taller than the 25th percentile for height probably do not have dyschondrosteosis, that a hereditary entity of Madelung deformity distinct from dyschondrosteosis exists, that patients with the isolated Madelung deformity may be short, and that marked shortening of the tibia relative to the femur suggests dyschondrosteosis. Langer (1965) had taken the view that most or all Madelung deformity is dyschondrosteosis. The most complete review of the subject of Madelung deformity was that by Anton et al. (1938). Rullier et al. (1968) observed dyschondrosteosis in mother and 2 daughters. Nassif and Harboyan (1970) described 2 brothers with Leri dyschondrosteosis, who also had middle ear deformities and conductive hearing loss. Three sisters had the skeletal deformity with normal hearing. Lisker et al. (1972) found a family informative for Rhesus and haptoglobin. No indication of close linkage was provided, however. Goepp et al. (1978) traced the disorder through 5 generations and observed male-to-male transmission in 14 instances. In all, 34 persons were affected.

Fryns and Van den Berghe (1979) presented the case of a male newborn with the typical Langer type of mesomelic dwarfism. The finding of a variable degree of Madelung deformity and mesomelic shortening in both parents and in the maternal family supported the hypothesis that this type of mesomelic dwarfism may be the clinical manifestation of a homozygous state for dyschondrosteosis; see 249700. Lichtenstein et al. (1980) reported male-to-male transmission. They commented that females showed dyschondrosteosis and Madelung deformity; males showed only the latter. Dawe et al. (1982) reviewed 13 patients with dyschondrosteosis from 8 families and concluded that inheritance is likely to be autosomal dominant but with only 50% penetrance. Stature was moderately reduced due to shortening of the bones of the leg. Radioulnar shortening could involve either both bones equally or the radius predominantly, in which case a typical Madelung deformity was seen. Tibiofibular disproportion was present in half the patients, 2 of them having severe deformity associated with tibia varum and a long fibula. It is recommended that patients with dyschondrosteosis be kept under surveillance during the growing period. Problems in the limbs, especially the legs, may require operations to equalize the length of the 2 bones. Jackson (1985) traced this disorder through 6 generations of a family, with 39 affected persons and 12 instances of male-to-male transmission. Several members belied the impression that females are always more severely affected than males. He suggested that the disorder is more frequent than generally realized and that an abnormally low ratio of forearm to upper arm length may be a valuable diagnostic clue. Ventruto et al. (1983) described a syndrome of skeletal dysplasia in 2 generations of a family. The affected persons had a balanced t(2;8)(q32;p23) translocation that was not found in 2 skeletally normal sibs. The affected persons were of normal intelligence. The proposita had short forearms with a short, bowed radius, cubitus valgus with limited motion at the elbows, fusion of C1 and C2 vertebrae, and other skeletal anomalies. Many of the features suggested dyschondrosteosis. Whatever the precise diagnosis, the findings may indicate mutation at the breakpoint on one of the involved chromosomes as the cause, or alternatively linkage of the responsible mutation as suggested by Hecht and Hecht (1984). A female-to-male ratio of about 4 to 1 and the fact that females are more severely affected suggested a peculiarity of the genetics. Gokhale et al. (1995) described a family in which 2 sisters with Leri-Weill dyschondrosteosis developed Hodgkin disease (236000) in late adolescence. Using HLA molecular typing, both sisters were found to have inherited a variant of the Hodgkin disease susceptibility allele, DPB1*0301, known as DPB1*2001. Because of the report by Ventruto et al. (1983) of a constitutional balanced reciprocal translocation between chromosomes 2 and 8 in LWD, Gokhale et al. (1995) conducted linkage studies of these 2 regions and excluded them as the site of the LWD gene in this family. A second cousin once removed of the 2 sisters developed Hodgkin disease at the age of 34 years. He apparently did not have LWD. The mother, the maternal grandmother, and her sister (the mother of the second cousin once removed), did have LWD. Gokhale et al. (1995) suggested that the LWD gene may be a predisposing factor to Hodgkin disease, which was also contributed to by the HLA susceptibility allele. In a Thai family with an autosomal dominant skeletal dysplasia with similarities to dyschondrosteosis, referred to as the Kantaputra type of mesomelic dysplasia (MDK; 156232), Fujimoto et al. (1998) demonstrated linkage to markers in the 2q24-q32 region. They were prompted to study this region because of similarities of the phenotype in the Thai family to that in the family reported by Ventruto et al. (1983) with t(2;8) translocation and dyschondrosteosis. Belin et al. (1998) and Shears et al. (1998) showed that Leri-Weill dyschondrosteosis is linked to DNA markers in the pseudoautosomal region (PAR1) on the X and Y chromosomes. They showed, furthermore, that the gene is deleted or the site of point mutations in cases of the disorder. Belin et al. (1998) demonstrated homozygous absence of the SHOX gene in a fetus with Langer-type mesomelic dysplasia (249700), which had previously been postulated to be the homozygous form of Leri-Weill dyschondrosteosis. Calabrese et al. (1999) described an X/Y translocation as the apparent basis of Leri-Weill dyschondrosteosis in a boy and his mother. FISH analysis with specific probes for SHOX and SRY (480000) displayed no signal on the derivative X, while one signal for SHOX was detected on the normal X chromosome in the mother and one signal each for SHOX and SRY was detected on the normal Y chromosome in the proband. The boy was first evaluated at the age of 7 years because of skeletal dysplasia. He showed short lower limbs. Radiologic studies showed enlargement of the ulna and radius and bowing of the knees. One year later, bowing of the radius and distal ulnar dislocation was found. The 34-year-old mother had short stature (150 cm), bowing of the radius, and bilateral subluxation of the distal ulna. Stuppia et al. (1999) reported a phenotypically male child with a 45,X karyotype who had dyschondrosteosis. FISH analysis with SHOX and SRY probes detected hemizygosity for SHOX and the presence of SRY on Xp. Molecular analysis suggested that the 45,X karyotype arose as a result of unequal crossing-over at paternal meiosis, translocating SRY onto Xp, and a separate event at maternal meiosis or in the early stages of zygote formation leading to the loss of the maternal X chromosome. Grigelioniene et al. (2000) performed mutation analysis of the coding region of the SHOX gene in 5 DCO patients and identified 3 novel mutations, 2 of which were missense mutations. Huber et al. (2001) studied 8 families with dyschondrosteosis and found point mutations in the SHOX gene in 5 families and deletions in 3. Combined with the results of their previous work (Belin et al., 1998), 10 of 16 families with this phenotype had deletions of the SHOX gene, while 6 of 16 had point mutations.

At Sat, 16 Feb 2002, jose luis quelho wrote: >
>Primipara na 24a. semana gestacional portadora de Enfermidade de
>Madlung (má formação congênita com deformidade do terço distal do rádio
>e luxação da articulação radio-carpal bilateral), rotina pré realizada
>até a presente data sem alterações digna de nota (inclusive
>ultrasonografia morfologica com doppler obstetrico). Solicito dos
>colegas informação sob esta enfermidade e riscos na gestação. Sem mais,
>atenciosamente
>
>--
>Jose Luis Quelho
>CRMMS 1982 - TEGO 370/97
>Aquidauana - MS
>

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