Delleman syndrome: report of a case with a mild phenotype

ARTICLE

Case report

A boy was born to unrelated healthy parents at 38 weeks gestation by Cesarean section due to fetal distress (slowing of the fetal heart beat, oligohydramnios, multiple placental hyperechogenic foci). The birth weight was 2,190 g, head circumference was 36 cm, and Apgar score was 9/9. The patient was referred to us for the presence of congenital cutaneous malformations at the age of 1 month.

Dermatological examination revealed cutaneous anomalies of two different types. The first were multiple roundish areas of focal dermal aplasia. The lesions were depressed, with a violaceous hue and had well defined borders giving them a peculiar punched-out appearance. Some were localized on the left side of the neck, on the left scapular area, and grouped on the paravertebral left lumbar area of the back. One lesion above the left external ear had a crescent shape (Fig. 1); two lesions on the left forearm featured anetoderma; a larger lesion was present on the posterior aspect of the left leg. Only one of these lesions was present on the right side (groin), while some were seen on the midline (nape of the neck, occiput, umbilicus). The atrophic areas were 3 to 60 mm wide, and showed no "cribriform", linear or reticular pattern of distribution. The second cutaneous abnormality was the presence of unusual skin appendages. A small exophytic round tumor was localized at the inner canthus of the left palpebral fissure (Fig. 1); two skin tags of about 2 cm in length were present in periumbilical situation; a pear-shaped exophytic tumor was on the dorsal aspect of the glans penis, giving the impression of a rudimentary supernumerary penis (Fig. 2); two other small tags were present on the neck.

Additional problems in this patient were the presence of pits and a hypertrophic frenulum on the upper lip, bilateral cryptorchidism with hypoplastic scrotum, and bifidity of the first left rib detected by chest radiographs. X-rays of the skull and of cervical, dorsal and lumbar vertebral column as well as cardiac, renal and transfontanel ultrasound examinations failed to reveal any abnormality. Cytogenetic studies showed normal 46,XY chromosomes. The study of the TORCH complex on maternal blood and histological examination of the placenta were non contributory.

The patient underwent the removal of some of the cutaneous lesions during his first few months of life. At histopathological examination the exophytic neoplasm on the penis was found to be a hamartoma composed of normal interconnected vascular channels embedded in delicate thin collagen bundles (normal spongy erectile tissue) in the absence of a urethra (Fig. 3). Serial sections showed the presence of a large nerve bundle composed of several smaller fascicles (Fig. 4). Skin tags were composed of verticalized collagen and smooth muscle bundles staining bright red in Masson trichromic stain, embedded in a loose edematous stroma composed by mucopolysaccharides.

Both ophthalmological and neurological examinations were repeatedly normal and follow-up at 18 months revealed normal physical and psychomotor development. Mild gastroesophageal reflux was clinically diagnosed. Cryptorchidism was surgically corrected at the age of 11 months. The intervention was complicated by repeated tearing out of the sutures at the right groin. The focal appearance of long, thick, and dark hair in both the areas of aplastic skin and elsewhere was observed (Fig. 5). The abnormal hair was located both within the aplastic areas and at their margin. Some focal dermal hypo/aplastic lesions remained unchanged, while others had an evident cicatricial evolution and resulted in normal, hypertrophic or anetodermic scar formation. Due to the clinical absence of neurological problems, the parents refused permission for RMN imaging of the central nervous system.

Comment

Delleman syndrome (also oculocerebrocutaneous syndrome or Delleman-Oorthuys syndrome) is a rare disorder marked by multiple congenital anomalies consisting of orbital cysts and micro/anophthalmia, malformations of the central nervous system, hypo/aplasia cutis and multiple skin appendages [1-3]. Although the syndrome has received little attention in the dermatological literature and well defined diagnostic criteria are missing, the cutaneous findings usually provide the main clues for a correct diagnosis. The patient reported is noteworthy due to the predominance of highly characteristic cutaneous features.

The ocular features of the syndrome mainly consist of hamartomatous orbital tumors or cysts. These are more often unilateral and may entirely replace the ocular bulb. Microphthalmia and eyelid coloboma are less frequent findings. MR and CT scan of the central nervous system allow the detection of multiple intracranial cysts or agenesia of the corpus callosum in most of the patients [4]. Other possible neurological abnormalities consist of cerebellar hypoplasia, hydrocephalus, and unilateral cerebral atrophy. Seizures and more or less severe psychomotor developmental delay are frequently observed during the follow-up of affected children. Undescended testes and skeletal abnormalities, such as skull defects and rib dysplasia, have been described in some of the patients [5].

Skin abnormalities represent the most constant finding in Delleman syndrome [6]. Although aplasia cutis is a rather nonspecific finding and may be associated with a number of different disorders [7], in Delleman syndrome it has a distinctive clinical presentation. The lesions consist of multiple small areas of dermal hypo/aplasia that have a characteristic depressed and punched out appearance. They are more frequently located on the face, neck, and trunk, with no linear or peculiar pattern of distribution. The invariably-associated skin appendages are pedunculated hamartomatous skin tags of variable dimensions that are more frequently localized on the face or in periorificial locations (e.g. around the orbit, the ear, and so on), sometimes in close proximity to the areas of dermal hypoplasia [4].

The distribution of both cutaneous and extracutaneous lesions in oculocerebrocutaneous syndrome lacks symmetry. Interestingly, a unilateral predominance, as observed in our patient, has previously been described [4]. Both types of cutaneous lesions are congenital and malformative in origin and are stable in time, except for the possible healing of aplasia cutis with scars or atrophy. No new lesions appear after birth and no report of malignant transformation of the skin tags has been reported to date. The cutaneous abnormalities are usually not severe or at least surgically removable, while the degree of ophthalmological and neurological involvement determines the prognosis of the disorder.

Due to the lack of MR or CT imaging in this patient we were unable to verify the presence of cerebral and ocular structural abnormalities. However, both neurological and ophthalmological clinical features of the disorder were absent. The diagnosis of Delleman syndrome was mainly based upon the cutaneous findings and was made after exclusion of other disorders featuring hypo/aplasia cutis and exophytic cutaneous hamartomas. A crescent-shaped skin defect around or above the external ear (Fig. 6) is highly suggestive of Delleman syndrome and has hence been proposed as pathognomonic [8]. Dermatological differential diagnosis of Delleman syndrome includes focal dermal hypoplasia (Goltz syndrome), microphthalmia with linear skin defects (MLS or MIDAS syndrome), oculoauriculovertebral spectrum (Goldenhar syndrome), preauricular skin defect, focal facial dysplasia (Brauer-Setleis syndrome), and encephalocraniocutaneous lipomatosis [9]. A possible clinical overlap with the oculoauricolovertebral spectrum [10] and with encephalocraniocutaneous lipomatosis [11] has been pointed out.

Goltz syndrome is uncommon in males but shares with Delleman syndrome the association of dermal hypo/aplasia and exophytic skin lesions. Skin manifestations are associated with a wide range of mesodermal defects and are characterised by "cribriform" dermal hypoplasia distributed in a linear or reticulated pattern along Blaschko lines, hyper- and hypopigmentation, fat herniations, papillomatous lesions in periorificial and flexural position, and teleangectases [12]. In MIDAS syndrome microphthalmia, orbital cysts and sclerocornea are associated with a dermal hypoplasia distributed along Blaschko lines, mostly extending from the bridge of the nose to the cheek; deletions or translocations of the short arm of chromosome X are the hallmark of the disorder [13]. Oculoauricolovertebral spectrum is mainly characterised by preauricular tags and pits, microtia, hemifacial microsomia, epibulbar dermoids, vertebral abnormalities [14]. In preauricular skin defect the lesions are localised along a line going from the preauricular region to the angle of the mouth, and are very similar to the so-called membranous aplasia cutis [15]. Brauer-Setleis syndrome features temporal skin defect with or without additional facial abnormalities [15]. Encephalocraniocutaneous lipomatosis is a controversial entity mainly characterised by cerebral, meningeal and cutaneous lipomatosis associated with cerebral malformations, mental retardation and seizures [16].

Delleman syndrome is a developmental defect of unknown origin. Since all the reported patients are sporadic cases of both sexes, it has been suggested that it may be due to a lethal gene surviving by mosaicism [17]. In Proteus syndrome, another probable lethal genetic disorder surviving by mosaicism, the genetic concept of "twin spotting" has been proposed to explain the possible association of dermal hypoplasia with localized tissular overgrowth [18]. In Delleman syndrome areas of focal dermal hypoplasia are constantly associated with the hamartomatous hyperplasia of the skin appendages. Hence, if the concept of twin spotting holds true, the seemingly opposite cutaneous anomalies in the Delleman syndrome could represent a further good example of this genetic phenomenon.

Article accepted on 14/8/00

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