Melorheostosis with ipsilateral nevus sebaceus (didymosis melorheosebacea)

ARTICLE

Melorheostosis (Léri’s disease) is a rare bone dysplasia characterized by localized hyperostosis and sclerosis [1, 2]. These lesions may be mono- or polyostotic. They affect mainly the long tubular bones, but the bones of the hands and feet and, sometimes, the axial skeleton may likewise be affected.

Nevus sebaceus is an epidermal nevus with a predominantly sebaceous component. The skin lesions are usually located on one side of the face or scalp but may also be bilateral and may involve the trunk and the limbs. They follow the lines of Blaschko with a strict midline demarcation.

Nevus sebaceus is considered to reflect mosaicism [3], and the same genetic concept has been proposed for melorheostosis [4]. Moreover, nevus sebaceus has been hypothesized to result from a postzygotic autosomal lethal mutation [5], and the same etiological mechanism was recently proposed for melorheostosis [6]. This assumption was based on 1) the mosaic arrangement of lesions, 2) the virtually always sporadic occurrence, 3) the sex ratio of 1:1 and 4) the observation that a diffuse involvement of an entire organ system never occurs [5-7].

We report here an unusual case of coexisting nevus sebaceus and melorheostosis and propose the concept of twin spotting as a possible common origin of the two conditions.

Case report

The patient was born in 1985. His parents were young at his birth, healthy and non-consanguineous. From birth on yellowish hairless elevated skin lesions were arranged in a linear and patchy pattern on the left side of his scalp and neck (Fig. 1). A biopsy showed hyperkeratosis, acanthosis and rather numerous sebaceous glands. Because this sebaceous nevus was believed to represent a precancerosis, it was surgically removed in its entirety when the patient was 14 years old. In the electroencephalogram, generalized epileptiform discharges were repeatedly seen in hyperventilation tests, but seizures never occurred. His mental development was normal. His height, weight and head circumference were within standard ranges.

At the age of 10 years, hypertension of 206/116 mm Hg on the right arm and 173/106 mm Hg on the left arm was noted at a routine physical examination at school. A subsequent check-up revealed a systolic ejection murmur along the left sternal border which extended to the back, as well as a diminished femoral pulse on both sides. Blood tests including plasma renin activity, aldosterone concentration and several hormonal parameters gave normal results. The electrocardiogram showed left ventricular hypertrophy. Radiography of the chest showed notching of ribs on both sides. A significant coarctation of the aortic isthmus was documented by echocardiography and aortography. Moreover, bone changes were detected by chest radiographs as well as by aortography (see below). The cardiovascular problem was successfully treated by a bypass graft repair bridging the ascending and descending aorta.

The bone changes found incidentally in the context of cardiological examination represented focal irregular densities and hyperostoses affecting the first, sixth and seventh rib on the left side (Fig. 2). Areas of increased radiodensity were noted in the fifth, sixth, seventh and eighth thoracic vertebrae (Fig. 3). Additional radiographs disclosed involvement of the left scapula, the left humerus and of some bones of the left hand, whereas the left forearm appeared to be unaffected (Fig. 4). These lesions were thought to be consistent with melorheostosis. Histopathological examination of a bone specimen taken from the left seventh rib revealed nonspecific hyperostotic, mainly lamellar bone formation, which definitely excluded the differential diagnosis of "polyostotic fibrous dysplasia".

A skeletal scintigram showed foci of increased radioactivity in the cervical and thoracal spine as well as in the first, sixth and seventh rib, the scapula and the humerus on the left side.

Discussion

More than 250 cases of melorheostosis have been reported since its first description by Léri and Joanny in 1922 [1, 7]. This skeletal disorder is due to a disturbance of both intramembranous and endochondral bone formation and therefore belongs to the group of "mixed sclerosing bone dysplasias" according to a classification as proposed by Greenspan [8, 9]. Periosteal hyperostosis along the cortex of long bones, resembling the dripping or flowing of candle wax, gave the condition its name (Greek melos  = limb, rhein  = to flow, osteon  = bone). Although the changes mainly affect the cortex, sclerotic lesions may extend into the spongiosa of bones [2]. Freyschmidt [7] described the diverse radiological patterns of the condition. The clinical picture varies to a large degree and may include pain, stiffness, deformity, limitation of joint movement, and shortness or, rarely, enlargement of affected limbs [2, 10]. All of these features are due to an abnormal formation of bone including ossification of soft tissues as frequently seen around joints, and the involvement of epiphyses [2].

Melorheostosis is found to be associated with anomalies of blood vessels or lymph vessels in 5-17 % of cases [11, 12]. Remarkably, the vascular abnormalities were always reported to be ipsilateral. They include capillary dysplasia, vascular nevi, arterio-venous shunts, varices, lymphectasia, aneurysms, and glomangiomas [10, 12-20]. Rarely, stenosis of a renal artery [11, 21] or occlusion of the dorsalis pedis artery [22] has been reported. Coarctation of the aorta in connection with melorheostosis has not been reported. On the other hand, coarctation of the aorta was reported in association with sebaceous nevus [23-25] although malformations of the cardio-vascular system are rarely associated with nevus sebaceus [26, 27]. Hence, any causal relationship between the patient’s coarctation of aorta and his melorheostosis and nevus sebaceus remains hypothetical.

The etiology and pathogenesis of melorheostosis are unknown. Two major hypotheses exist: 1) the bony lesions have been ascribed to sclerotomes which are areas of segmental sensory innervation of the skeleton [28], or 2) the bone lesions are proposed to originate from a postzygotic mutation occurring during embryogenesis [4, 7]. We prefer the second hypothesis, and the present case of coexisting melorheostosis and sebaceous nevus can be taken as an additional argument in favor of this concept.
Nevus sebaceus is a well known example of somatic mosaicism [5, 27, 29]. Its occurrence in combination with ipsilateral melorheostosis may indicate a common mechanism of origin. Theoretically, one could assume a pleiotropic effect of one single mutation, but this is very unlikely because otherwise melorheostosis should be observed more often in association with Schimmelpenning syndrome (sebaceous nevus syndrome). Rather, we should like to propose the concept of twin spotting or didymosis (Greek didymos  = twin) [30] to explain the temporal and spatial co-occurrence of melorheostosis and nevus sebaceus as noted in this case. Remarkably, some vertebral foci of increased radioactivity as documented in a scintigram were in close proximity to the nuchal part of nevus sebaceus. Twin spots are defined as paired areas of tissue being homozygous for different recessive mutations, occurring on a background tissue that is heterozygous for either mutation [3]. The embryo would carry two different mutant alleles at one gene locus (compound heterozygosity) or two different mutations are localized at different regions on either of a pair of homologous chromosomes (double heterozygosity). Postzygotic recombination occurring at an early developmental stage would give rise to two different populations of cells homozygous for either mutation. Other possible examples of allelic or nonallelic didymosis include vascular twin nevi, coexisting hyperplasia and hypoplasia in Proteus syndrome, phacomatosis pigmentokeratotica, phacomatosis pigmentovascularis, and cutis tricolor [31]. Accordingly, we propose the term didymosis melorheosebacea to describe the present unusual co-occurrence of skin and bone lesions.

CONCLUSION

We thank Dr. Adam Greenspan, Sacramento, California, USA, who reexamined the X-rays of this patient and confirmed the diagnosis of melorheostosis.

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