332332~~~~~~~~~~~~~~~~~~~~~~~~~~~~~J7Med Genet 1992; 29: 332-337 SYNDROME OF THE MONTH W.eaver syndrome T R P Cole, N R Dennis, H E Hughes In 1974 Weaver et al' described two unrelated born at 40 to 41 weeks' gestation. Cases 1, 2, children with accelerated growth, advanced and 3 were born by caesarean section because bone age, and a characteristic facial appearance. of fetal distress, but there were no serious The condition subsequently became known as neonatal complications. Paternal ages were 33, the Weaver-Smith syndrome (WSS). Since the 26, 35, and 32 years and maternal ages 39, 25, original report, approximately 30 further cases 28, and 23 years, respectively. have been described. It is still debatable if the syndromes of Marshall-Smith (MSS) and Weaver-Smith (WSS) are on24or separate Review of clinical features entities,516 but at present most authors believe GROWTH they are different conditions.' Here we briefly In WSS there is increased prenatal (table 2) include details on four new cases of Weaver- and postnatal weight (fig 3). Birth length and Smith syndrome and review the published OFC seem to be similarly affected (figs 4 and reports. 5), but there are fewer data on these particular parameters. On reviewing 25 published cases 1 -8and the four new cases in this Case reports (figs 1-6) report, birth length and OFC are increased Clinical details of four new cases of WSS are above the 97th centile in 15/18 and 8/15 chil- summarised in table 1. All are male and were dren, respectively. Postnatal height and OFC (c) Institute of Medical Genetics, University Hospital of Wales, Heath Park, Cardiff CF4 4XW. T R P Cole H E Hughes Wessex Regional Genetic Service, The Pr'incess Anne Hospital, Southampton S09 4HA. N R Dennis CorrespondenceCorrspodenctotoDrDr Cole.Cle.Figure 1 Case 1 at ages (a) 4 months, (b) 12 months, (c and d) 5 years. Weaver syndrome 333 (a) Pr.~~~~~~ w ~ ~~~~~_ . ,-'' _~.r" , (b) (d) (c) FLr'I1 2_ *C(s;I 2 ;at a,EaLISand11 b 3 months, c anici td 5 Years. Kg lb cm in Boys' weight 190 190 Boys' height 80 0 170 170 ,' / 70 )_ ~~~~~~~~~~~//150 60 130 iO 50 // 110 40 0~~~~~~~~ 90 1104 < II|I0 I I,,/I, O 30 70 20 50 30 10 10 2 50 L I 6 1 3 5 7 9 11 13 15 17 19 130 5 7 9 11 13 15 17 19 Age (years) Age (years) Figure 3 Weight chart cases 1-4. Figure 4 Height chart cases 1-4. 334 Cole, Dennis, Hughes cm CRANIOFACIAL FEATURES (TABLE 1) In infancy the face is round with retrognathia 62 Mean (50th centile) - and a small but very prominent chin, which 58 S often has a central dimple (figs 1 and 2). In +2SD (98th centile) °i childhood, the face becomes longer and less 54 distinctive,'8 although the latter may reflect with 50 - 0- - lack of experience in assessing patients - 0 * WSS in older age groups. In mid-childhood 46 ,-- there are similarities between the facial gestalt / .-.fl717 of Sotos syndrome and WSS (figs Id and 2c). 42 Cases 1, 2, and 4 in the present series were having Sotos syndrome. 38 initially diagnosed as 34 LIMB AND SKELETAL ANOMALIES In I -_-1 _v 1 3 5 7 912 15 18 2 4 6 81014 18 In the two original cases,' prominent fingertip (.u- Months - -!-- Years - ( pads (fig 6) and deep set nails were described. These features can also be seen on examination Figure 5 Occipitofrontal circumference charts cases of the toes (fig 6). Camptodactyly, although 1-4. common (11/16, Ardinger et al7) is by no means a consistent finding and was seen in only one of the four present cases. Cases 1, 2, and 3 had a typical pattern of overriding toes (fig 6) which also appear to be increased (usually >97th required surgical correction in case 2. This centile), but in the authors' own experience, feature may just reflect crowding of the toes, which is in keeping with the findings of but could be analogous to the camptodactyly Majewski et al,9 it seems that weight is more seen in the hands. Similar toe abnormalities significantly increased than height (figs 3 and have been identified in previous case re- 4). The overgrowth in the cases of Bosch- ports'247 '20 in addition to a variety of foot Banyeras et al2 and Weisswichert et all2 was deformities, such as pes cavus'5 and club feet.7 less dramatic, but both children had cardiac Knee and elbow joints are often rather large lesions. Unlike Sotos syndrome, the most with limitation of extension. Radiological ex- commonly differentiated overgrowth con- amination of these joints may show metaphy- dition, OFC in WSS does not appear to be seal flaring. > 97th centile in all cases. Five patients out of 29 have post-infancy OFC values between the 50th and 97th centiles. BEHAVIOUR AND DEVELOPMENT The growth pattern in adolescence and It is likely that there has been ascertainment through to adulthood has not yet been defined, bias towards the severe end of the develop- but the adult cases reported to date have mental spectrum in the early descriptions. All achieved heights of 209-5 cm (+ 5 2 SD),7 seven cases of WSS reported by Ardinger et al7 187 cm (+ 3.5 SD),'8 and 161 cm (50th were developmentally delayed on early assess- centile).'6 However, the diagnosis of WSS in ments, although one patient subsequently the latter case cannot be confirmed on the achieved an IQ score of 100 and one other information provided. These limited data patient was described as being within the low would seem to suggest that adult height in average range. Cases 1 and 2 of the present WSS may be greatly increased; however, these series fall into the category of borderline or reported cases were diagnosed as adults when mild mental handicap and together with case 4 tall stature may have biased ascertainment. show marked early motor and speech delay. Figure 6 Case I showing prominent finger tip pads, prominent pads on toes, and overriding 4th toe. Weaver syndrome 335 Table 1 Clinical summary: four new cases of Weaver-Smith syndrome There are suggestions in published case re- Case 1 Case 2 Case 3 Case 4 Ref 7 ports that muscle tone may increase with time. In the series of patients reported by Ardinger Age 4y Ilm 5y Im 7m ly 1Om Birth weight (g) 5500 4200 4500 4200 et al,7 those patients with hypotonia were aged (SD) (+3-8) (+1-3) (+2 3) (+1-3) 0 to 24 months while the hypertonic patients Birth length (cm) 61 56-6 (SD) (+5-7) (+3-4) were aged between 5 and 39 years. Lower limb Birth OFC (cm) 39 38 reflexes in cases 2, 3, and 4 of the current (SD) (+1-5) (+ 1-0) Broad forehead + + + + 18/19 report are rather brisk, although the plantar Round face in + + + + response is still flexor. Case 7 described by infancy Micrognathia + + + + 17/19 Ardinger et al' had a progressive spasticity Prominent philtrum + + + + 10/14 resulting in the patient becoming wheelchair Large ears + + + + 15/17 (length cm) (7.1) (6-7) (6-8) bound in adulthood. Myelography in this Hypertelorism + + + + 19/19 patient showed what was described as (ICD cm) (3-5) (3-9) (3-5) Large hands + + + + 'questionable' spinal stenosis. Mohonen and Deep set nails + - + + 9/10 Menezes'9 reported a case ofWeaver syndrome Prominent finger/toe pads + - + + 6/9 Overriding toes + + + with instability of the cervical spine and specu- Syndactyly - + lated that this might explain progressive spas- Genital anomalies + + + Tone Normal Reduced Normal Reduced T10/18 ticity. Case 2 of the present series has fusion of 1 5/18 the second and third cervical vertebrae but no Reflexes Normal Brisk Brisk Brisk other axial anomaly. It is speculative whether progressive involvement of the spinal cord, on a background of 'central hypotonia', is the underlying cause of these lower limb signs. Table 2 Comparative birth measurements in three overgrowth syndromes. ADDITIONAL FEATURES Weaver Sotos' Marshall" Weaver et al,' in their original paper, reported the presence of short penile in both Weight>97th entile 14/29 6/41 1/11 length > 90 cen their patients. This feature does not appear Weight<50th centile 3/29 4/41 6/11 to be a common finding in subsequent Length> 97th centile 15/18 23/27 5/10 > 90 cen cases, although cryptorchidism has been OFC> 97th centile 8/15 12/27 3/7 reported.I1216 Inguinal and umbilical herniae > 90 cen are common, the latter present in cases 2 and 3 *'Cut of' at 90th centile. of the current series. In addition, case 2 had a very high left testis and cases 1 and 3 had hydroceles in infancy. These deficits are now improving. At present, Hirsutism, which is more usually associated case 3 appears to be developing normally with MSS,5 has been reported by Jalaguier et (table 3). al4 in a patient where the diagnosis of either Speech in WSS is not only delayed, but is WSS syndrome or MSS syndrome is ques- also often described as slurred or dysarthric tioned. However, this feature has also been and the tone of the voice is rather hoarse and documented by Stoll et al'6 in a patient where low pitched. the diagnosis of WSS seems certain. Behavioural problems are common in WSS Other overgrowth syndromes such as Sotos and poor concentration and temper tantrums syndrome, Beckwith syndrome, and hemi- may be particularly difficult to manage.