Arch Dis Child: first published as 10.1136/adc.43.227.102 on 1 February 1968. Downloaded from

Arch. Dis. Childh., 1968, 43, 102.

The Rubinstein-Taybi Syndrome: a Report of Two Cases

M. A. SALMON From the Department of Paediatrics, St. Helier Hospital, Carshalton, Surrey

In 1963, Jack Rubinstein and Hooshang Taybi revealed port-wine naevi over the sacrum and forehead described a group of 7 children whose external (naevus flammeus). The thumbs were very large and appearance was sufficiently remarkable to be con- flattened, and there was radial deviation of the terminal sidered as a new syndrome, and within three years phalanx. The terminal phalanges of the other digits further cases were presented (Coffin, 1964; Latuff, were bulbous. The great toes were very large and Yamin, and flattened. The pattern of palmar dermatoglyphs was Quintero, 1964; Job, Rossier, and de unusual (see below). The facies were characteristic, Grandprey, 1964; Jancar, 1965; Robinson, Miller, with epicanthic folds, simple ears, and a beaked nose. Cook, and Tischler, 1966; Johnson, 1966; Kushnick, There was an antimongoloid slant to the palpebral fis- 1966; Berg, Smith, Ridler, Dutton, Green, and sures and an apparent resemblance to the Treacher- Richards, 1966). Most of these cases were from Collins syndrome (Collins, 1900). The nasal septum was North America, and the purpose of this paper is to markedly deviated, and together with an abnormally present a further two cases, one from the United narrow glottis accounted for the swallowing difficulties

Kingdom and the other from Afghanistan, both encountered during feeds. There was a bifid xiphoid copyright. being diagnosed at birth. The constellation of cartilage and a minor degree of hypospadias. A cardiac congenital anomalies murmur became audible at the left sternal edge after enumerated in the original the first month of life and the electrocardiograph showed paper includes abnormal thumbs and great toes, a right bundle-branch block. characteristic facies, and mental retardation. Car- Investigations. The following investigations produced diac, renal, skeletal, and first arch defects were also normal results: haemoglobin, white cell count, serum described and more recently abnormal dermato- electrolytes, urea, calcium, phosphorus, magnesium, glyphic patterns have been found (Robinson et al., liver function tests, urinary sodium, potassium and

1966; Berg et al., 1966). There is now sufficient calcium, 17-ketosteroids, 17-ketogenic steroids, urinary http://adc.bmj.com/ evidence to state that the association of congenital chromatography for amino acids and sugars, skull x-ray anomalies as originally described constitutes a films, bone age, intravenous pyelogram, and micturating definite syndrome of unknown aetiology, and its cystogram. Buccal chromatin negative. Chromosome early recognition by the physician is important studies revealed a normal male karyotype. when the problem of counselling the parents is Case 2. A.H., a male infant (Fig. 5a and b), was considered. admitted to the special care unit shortly after birth on account of congenital anomalies and poor general Case Reports condition. He was the second child of parents who on September 30, 2021 by guest. Protected originally came from Afghanistan. He was delivered Case 1. P.P., a male infant (Fig. 1-4), was admitted by caesarean section for disproportion at 38 weeks' to the special care unit on the first day of life on account gestation. There was no history of teratogenic agents of apnoeic attacks associated with the first feed. He during the first trimester of pregnancy and no significant was the product of a normal second pregnancy (English family history of previous abnormalities. Birthweight parents) and uncomplicated spontaneous delivery at 2 83 kg. (6 lb. 4 oz.). 38 weeks' gestation. There was no history ofteratogenic Clinical examination revealed bilateral exophthalmos, agents during the first trimester of pregnancy. There craniostenosis of the sagittal and metopic sutures, and was a family history of meningomyelocele and hydro- resultant scaphocephaly. There was maxillary hypo- cephalus in a first cousin and mental retardation with plasia and a beaked nose with marked septal deviation, congenital deaf-mutism in the father's brother. Birth- The appearance was compatible with that ofcranio-facial weight 2-55 kg. (5 lb. 10 oz.). Clinical examination dysostosis (Crouzon's disease). The thumbs and great toes were identical with those described in the previous Received July 27, 1967. case and the other digits likewise. Palmar dermato- 102 Arch Dis Child: first published as 10.1136/adc.43.227.102 on 1 February 1968. Downloaded from

The Rubinstein-T'aybi Syndrome 103 _ ....

FIG. I.-ase 1. (a) Charautteristic facies. (b) Profile. glyphs were abnormal (see below). The palate was the skull in the region of the greater wing of the sphenoid high arched and the glottis narrow. The uvula was bone. There were no cardiac anomalies, but a posterior copyright. bifid. The ears were simple and very low set. This urethral valve had given rise to bilateral ureteric dilatation. infant died at the age of 2 weeks of bronchopneumonia, The caecum and ascending colon were attached by an and post-mortem findings included a right-sided choanal abnormally long mesentery. atresia and a symmetrical bony defect on either side of Investigations. The following investigations produced http://adc.bmj.com/ on September 30, 2021 by guest. Protected

.....-Case1. (a) H w c istic...... a... Plantar a FIG. 2.---ase 1. (a) Hand with characteristic thumb and palmar creases. (b) Plantar aspect of leftfoot. 8B Arch Dis Child: first published as 10.1136/adc.43.227.102 on 1 February 1968. Downloaded from

104 M. A. Salmon

FIG. 3.-Case 1. Left ear. FIG. 4.-Case 1. Characteristic naevus over sacrum. copyright. normal results: haemoglobin, white cell count, serum Palmar dermatoglyphs. The palmar crease pat- electrolytes, urea, calcium, phosphorus, alkaline phos- tems were abnormal in both these infants. There was a phatase, and liver function tests. Buccal chromatin double transverse palmar crease in the first case and a negative. Chromosome studies revealed a normal male single transverse crease in the second case. The unusual karyotype. loop carpal pattern found in the thenar/first interdigital http://adc.bmj.com/ on September 30, 2021 by guest. Protected

FIG. 5.-Case 2. X-ray pictures (a) of hand and (b) offoot show bony abnormalities. Arch Dis Child: first published as 10.1136/adc.43.227.102 on 1 February 1968. Downloaded from

The Rubinstein-Taybi Syndrome 105 TABLE Incidence of Characteristic Anomalies in 36 Reported Cases

Rubinstein and Taybi (1963); Coffi Berg et al. Johnson Robinson Kushnick Present Taybi and (1964) (1966) (1966) et al. (1966) (1966) cases Rubinstein (1965) Total. 13 6 6 6 2 1 2 Sex .. . 8 59 36 39 69 26 49 1i 19 19 26' Broad thumbs and toes 13 6 6 6 2 1 2 High arched palate...13 6 6 6 1 1 2 Beaked nose . .. 10 6 5 5 - 1 2 Nasal septal deviation. . . 2 - - 0 - - 2 Abnormal ears .. . 6 3 6 - 1 2 Antimongoloid slant .. . 11 6 3 6 2 1 2 Epicanthus .. .4 6 1 4 1 1 2 Naevus flammeus .. 2 4 2 5 - - 1 Mental retardation .. . 13 6 6 6 2 1 ? Skeletal retardation .. . 13 6 - 6 - - 0 Dwarfism . .13 0 6 6 0 1 ? Abnormal palmar pattern - 0 6 - 2 - 2 area in both cases described by Robinson et al. (1966) anomalies, micrognathism, and macrostomia are was present in both these cases, and appears to constitute usually absent (Hunt and Smith, 1955). Kushnick an important diagnostic stigma. A distal palmar (1966) and Berg et al. (1966) have, however, each triradius (t), similar to that found in Down's syndrome, described cases in which occurred. was also present in each case and the angle between micrognathism this and the a and d triradii (atd) (Penrose, 1963) In the second case described in this paper apparent was 176 and 170 degrees, respectively. In the first case mandibulo-facial dysostosis is accompanied by cranio- there was an extra triradius on the end of the thumb, and facial dysostosis (Crouzon's syndrome) so that it is this agrees with the cases described by Berg et al. (1966). possible that a variable degree of mandibulo-facio- copyright. It thus appears that the palmar dermatoglyphs in this cranial dysostosis is important as a component ofthe syndrome are characteristic and unusual, and Berg et al. Rubinstein-Taybi syndrome. There is also a superfi- (1966) give a detailed discussion of this point. cial resemblance to the facies found in the Haller- mann-Strieff syndrome and in some cases of Characteristic Anomalies of Syndrome 'bird-headed' dwarfism (Seckel, 1960), but in these Broad thumbs and toes. The unusual thumbs cases anomalies of the thumbs and great toes are not and toes appear to be unique and can be recognized found. at birth (Fig. 2 and 5) (Barsky, 1951; Thomas, 1936; http://adc.bmj.com/ Thomsen, 1927). Characteristically the digits Mental retardation. This is invariable though are short with bulbous terminal phalanges and testing was not performed in the two present cases. increased curvature of the nails. The terminal In one of the cases described by Coffin (1964) phalanges of the thumbs and great toes are greatly there was partial agenesis of the corpus callosum, flattened, and there is radial deviation ofthe terminal a deficiency of central white matter, and increased phalanx of the thumb. The name 'talpism' was thickness of the overlying cortex. Histology coined by Coffin (1964) to describe the appearance revealed immature dystrophic neurons, with poor of the thumbs, and in this context one recalls the differentiation of their layers. Further studies are on September 30, 2021 by guest. Protected appearance of the hands of the mole (Talpa essential before pronouncement can be made as to europaea L.). the significance of these findings. Characteristic facies. The facies are easily Other findings. These are numerous and recognized on account of the antimongoloid slant many anomalies appear so frequently that their to the palpebral fissures, the beaked nose, epicanthic occurrence can hardly be fortuitous. In 14 patients folds, and ears which are often simple, low set, or pigmented naevi were noted on the forehead (naevus rotated (Fig. la and b). The palate is invariably flammeus) or sacrum (Fig. la and 4). Minor high arched. The appearance of the face suggests skeletal anomalies including scoliosis, kyphosis, bifid a first-arch syndrome similar to mandibulo-facial xiphoid cartilage, fused ribs, pectus excavatum, and dysostosis (Treacher-Collins or Francheschetti- pectus carinatum were frequently reported, and one Klein syndromes), but colobomata, middle ear patient (Taybi and Rubinstein, 1965) had a Arch Dis Child: first published as 10.1136/adc.43.227.102 on 1 February 1968. Downloaded from

106 M. A. Salmon meningomyelocele. In all patients in whom it was recognized at birth, and indeed should be as mental tested, the electroencephalogram was abnormal. retardation is invariable. The tracing was usually described as being diffusely I wish to thank Dr. Trevor Wright and Dr. J. N. abnormal with poorly organized 3-7 cycle per O'Reilly for permission to describe their cases. second waves. In one case (Robinson et al., 1966) there was some paroxysmal activity suggesting a RERENCES diagnosis of epilepsy. Kushnick (1966) described Barsky, A. J. (1951). Congenital anomalies of the hand. J. Bone abnormal and verbal in Jt Surg., 33-A, 35. gait aphasia his case. Berg, J. M., Smith, G. F., Ridler, M. A. C., Dutton, G., Green, Cardiac lesions were discovered in about one-quarter E. A., and Richards, B. W. (1966). On the association of broad of the cases and patent ductus arteriosus was thumbs and first toes with other physical peculiarities and mental retardation. J. ment. Defic. Res., 10, 204. confirmed in three and endocardial fibrosis in one. Coffin, G. S. (1964). Brachydactyly, peculiar facies and mental Abnormalities of the urogenital system appear retardation. Amer. J. Dis. Child., 108, 351. Collins, E. T. (1900). Case with symmetrical congenital notches frequently, and specific anomalies reported include in the outer part of each lower lid and defective development of absent or extra kidneys, posterior urethral valve, the malar bones. Trans. ophthal. Soc. U.K., 20, 190. Hunt, P. A., and Smith, D. I. (1955). Mandibulo-facial dysostosis. abnormal shape of the bladder, hypospadias, or Pediatrics, 15, 195. angulation of the penis. Jancar, J. (1965). Rubinstein-Taybi's syndrome. J. ment. Defic. The aetiology of the Rubinstein-Taybi syndrome Res., 9, 265. Job, J. C., Rossier, A., and de Grandprey, J. (1964). etudes sur is unknown. In all cases in which chromosome les nanismes constitutionnels. II. Le syndrome de Rubin- studies were undertaken a normal karyotype was stein et Taybi. Ann. Pediat., 11, 646. Johnson, C. F. (1966). Broad thumbs and broad great toes with found. No specific biochemical disorder has been facial abnormalities and mental retardation. J. Pediat., 68, demonstrated and there is no common history of 942. Kushnick, T. (1966). Brachydactyly, facial abnormalities, and teratogenic agents. The condition is easily recog- mental retardation. Amer. J. Dis. Child., 111, 96. nized at birth, and this is important as mental Latuff, H., Yamin, G., and Quintero, L. D. (1964). Alteraciones retardation is invariable. de los dedos de manos y pies, anomalias faciales y retarde mental. Bol. Hosp. Ninos, 6, 195. Penrose, L. S. (1963). Finger prints, palms and chromosomes. Nature (Lond.), 197, 933. Summary Robinson, G. C., Miller, J. R., Cook, E. G., and Tischler, B. (1966). Broad thumbs and toes and mental retardation. Amer. J3. Dis. copyright. Two new cases ofthe Rubinstein-Taybi syndrome Child., 111, 287. are described. It is suggested that definition of Rubinstein, J. H., and Taybi, H. (1963). Broad thumbs and toes and facial abnormalities. ibid., 105, 588. the syndrome requires abnormal thumbs and great Seckel, H. P. G. (1960). Bird Headed Dwarfs. Thomas, Spring- toes, a characteristic facies in which a variable field, Illinois. Taybi, H., and Rubinstein, J. H. (1965). Broad thumbs and toes degree of mandibulo-facio-cranial dysostosis is and unusual facial features. Amer. J7. Roentgenol., 93, 362. important, and mental retardation. The palmar Thomas, H. B. (1936). Partial gigantism. Amer. J3. Surg., 32, 108. dermatoglyphic pattern is unusual and may even Thomsen, 0. (1927). Hereditary growth anomaly of the thumb.

prove to be diagnostic. The condition can be Hereditas (Lund), 10, 261. http://adc.bmj.com/ on September 30, 2021 by guest. Protected