Rubinstein–Taybi Syndrome and UlerythemaOphryogenes in a 9-Year-Old Boy

Pilar Gomez Centeno, M.D., Elena Roso´n, Ph.D., Carmen Peteiro, Ph.D.,Ma. Mercedes Pereiro, Ph.D., and Jaime Toribio, Ph.D.

Department of Dermatology, General Hospital of Galicia, Faculty of Medicine, Santiago de Compostela, Spain

Abstract: Rubinstein–Taybi syndrome is characterized by the pres-ence of a peculiar facies, mental retardation, and broad thumbs and greattoes. Several associated cutaneous abnormalities have been reportedwith this syndrome. Ulerythema ophryogenes is a form of follicular kera-tosis associated occasionally with other ectodermal defects and congen-ital anomalies. We describe a 9-year-old child with Rubinstein–Taybi syn-drome and ulerythema ophryogenes. This association has not beendescribed previously to our knowledge.

In 1963 Rubinstein and Taybi (1) described a syn-drome observed by them in seven children consisting ofmental retardation, a peculiar facies, and broad thumbsand great toes. Cutaneous manifestations are observed ina variable proportion of such patients. These manifesta-tions are not diagnostic, and indeed may often be merelycoincidental (2–9).

We describe a 9-year-old boy with the malformationscharacteristic of Rubinstein–Taybi syndrome and cuta-neous manifestations compatible with ulerythema oph-ryogenes. This association has not been reported pre-viously.

CASE REPORT

The patient was a 9-year-old boy with healthy noncon-sanguineous parents. He had multiple abnormalities atbirth (pulmonary artery hypertension, high-arched pal-ate, micrognathia). Delivery was by cesarean section inview of acute fetal distress (meconium in the amnioticfluid). APGAR scores (0, 5, and 10 minutes) were 0, 2,and 5, respectively. The patient subsequently showedretarded psychomotor development and growth, togetherwith lactose intolerance.

On physical examination he had a prominent foreheadwith high hairline; asymmetric antimongoloid slant ofthe palpebral fissures with mild ptosis; hypoplastic nasalalae, terminating above the septum; a small mouth withsmall, incorrectly positioned teeth and high-arched pal-ate; large dysplastic auricles placed low on the head;hypoplastic scrotal sacs and undescended testes; broadand short thumbs and great toes (Fig. 1). These charac-teristics confirmed the proposed diagnosis of Rubinstein–Taybi syndrome. From 1 year of age his face was re-markable for erythema and numerous hyperkeratoticfollicular papules on the cheeks and in the medial andlateral regions of the eyebrows, with consequent alopecia(Fig. 2).

The blood and urine analyses were normal, except forhigh hepatic enzyme activity. Thyroid hormone levelswere normal. He tested positive for hepatitis C. Electro-cardiograms and cardiac ultrasonography were normal.Neither magnetic resonance scanning of the brain andspinal cord nor detailed skeletal radiography revealedabnormalities apart from a slight thickening of the distalphalanx of the great toes. An ophthalmologic examina-tion demonstrated poor visual acuity and coloboma of

Address correspondence to Jaime Toribio, Departamento de Der-matologı´a, Facultad de Medicina, C/. San Francisco, s/n, 15705 San-tiago de Compostela, Spain, or e-mail: mejaime@usc.es.

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the left iris, retina, and choroid. The karyotype was 46XY. Biopsy specimens of cutaneous lesions showed fol-licular hyperkeratosis, dilation of dermal blood vessels,and moderate perivascular lymphocyte infiltration.

The mother rejected treatment other than skin hydra-tion, and we therefore recommended a cream containing3% urea.

DISCUSSION

Rubinstein–Taybi syndrome is a rare disorder that mayoccur in either sex. Its etiology is unknown and it gen-erally occurs sporadically, though some cases are clearlydue to autosomal dominant inheritance (10). About 25%of patients show a deletion at 16p13.3 (11–13). It ischaracterized by mental retardation, a peculiar facies,and broad thumbs and great toes. The most evident mal-formation is typically a beaked nose, though this is oftennot apparent until late childhood (13).

A number of cutaneous disorders have been reportedin association with Rubinstein–Taybi syndrome, themost frequent of which are hirsutism of the shoulders

and back (2–5) and keloid formation (whether spontane-ous or as a result of trauma) (2–5,7,8). Other cutaneousdisorders reported include capillary hemangiomas (2,3,6), cafeau lait spots (2), seborrheic dermatitis (5), pie-baldism (6), pilomatricomas (3,14), abnormal dermato-glyphics (4,5,9), and in one case, follicular hyperkerato-sis on the arms (9).

Patients with Rubinstein–Taybi syndrome do not ap-pear to be at increased risk for any particular type ofneoplasm, but a recent study has indicated an abnormallyhigh prevalence of tumors derived from the brain andneural crest (14). Other disorders reported in associationwith Rubinstein–Taybi syndrome include ocular, car-diac, brain, bone, digestive system, and genitourinaryabnormalities.

Ulerythema ophryogenes (keratosis pilaris atrophi-cans) is a form of follicular keratosis typically arising inchildhood and affecting the cheeks and the medial andlateral parts of the eyebrows, where it may cause alope-cia. It is a congenital ectodermal defect of the piloseba-ceous system (15). It is frequently associated with fol-licular keratosis of the arms and legs (which is itself afrequent disorder), and with other ectodermal and geneticdisorders, including woolly hair (15), internal anomaliesand atopy (16,17) and the syndrome comprising fol-licular ichthyosis with alopecia and photophobia (andtypically also follicular hyperkeratosis, though not ery-thema) (18). However, it is most frequent in patients withNoonan syndrome (15,19,20), and indeed some authorshave proposed that it be considered a cutaneous markerof this syndrome. It has also been reported in associationwith cardio-facio-cutaneous syndrome (21), with mul-tiple congenital anomalies that are difficult to assign to aparticular syndrome (22), and in one case in a patientwith monosomy 18p (23).

It has been suggested that ulerythema ophryogenesand follicular keratosis, like Rubinstein–Taybi syn-drome, are transmitted by autosomal dominant inheri-tance (15,17,19). Other authors have suggested a rela-tionship with vitamin A deficiency (16,19,21), despitethe fact that replacement therapy is ineffective. Of thevarious treatments that have been applied to date (includ-ing corticoids, salicylic acid, keratolytic drugs, and reti-noids), none appears to be very effective. Recently Lay-ton and Cunliffe (24) reported a good response after 6months’ treatment with isotretinoin at 1 mg/kg/day.

The patient described in this article had Rubinstein–Taybi syndrome in association with cutaneous lesionscompatible with ulerythema ophryogenes. The lesionsaffected the eyebrows and cheeks and had been presentsince early infancy. We are unaware of previous reportsof this association, although a patient with Rubinstein–

Figure 1. Patient exhibits a broad big toes.

Figure 2. Alopecia in eyebrows.

Centeno et al: Rubinstein–Taybi Syndrome135

Taybi syndrome and follicular keratosis has been de-scribed (9).

Both disorders are probably genetic in origin. Onepossibility is that the genetic defects responsible are lo-cated on the same chromosome. The evaluation of otherpatients with Rubinstein–Taybi syndrome is necessary totry to ascertain the frequency of this association and ifthis cutaneous feature has been merely overlooked or istruly a novel presentation.

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