97 Sotos Syndrome
Cerebral gigantism
Increased birth weight and length, excessive growth in infancy, large hands and feet, advanced bone age, and distinctive facial features including macrocrania, re- ceding hairline, apparent hypertelorism, and promi- nent mandible
Frequency: Rare (over 300 published cases).
Genetics
Autosomal dominant (OMIM 117550), most cases sporadic; the disease gene NSD1 maps to chromo- some 5q31; allelic to Weaver syndrome and to some Beckwith-Wiedemann cases. Another locus maps to 11p15.5 (allelic to Beckwith-Wiedemann syndrome).
Clinical Features
• Increased birth weight (mean birth weight 3.9 kg) and length (3.2 SD above mean), large hands and feet at birth
• Macrocrania, dolichocephaly, prominent fore- head, receding anterior hairline
• Apparent hypertelorism (due to narrow temples), strabismus (40%), downward slanting palpebral fissures, anteverted nares
• Arched palate, early eruption of teeth (50%)
• Pointed, large jaw
• Coarsening of facial features with age
• Accelerated growth during the first four years of life, tall stature, disproportionately long limbs
• Congenital heart defect
• CNS anomalies (ventriculomegaly, absent corpus callosum), delay in walking, speech delay, usually attainment of normal intelligence
• Joint laxity may cause pes planus, genu valgum, and scoliosis
• Increased frequency of solid tumors (Wilms, hepatocellular carcinoma, neuroblastoma, lung carcinoma, sacrococcygeal teratoma)
Differential Diagnosis
• Other overgrowth syndromes (e.g., Weaver syn- drome; Marshall-Smith syndrome; Bannayan- Riley-Ruvalcaba syndrome)
Radiographic Features Skull
• Large, dolichocephalic skull, with prominent fore- head
• Small sella turcica relative to large head
• Posteriorly inclined dorsum of sella turcica
• Premature eruption of teeth Generalized Skeletal Abnormalities
• Advanced bone age Hands and Feet
• Disproportionately large hands and feet
• Relatively short distal phalanges compared with proximal phalanges and metacarpals
• Dysharmonic carpal bone maturation
• Pes planus
• Syndactyly Spine
• Kyphoscoliosis Extremities
• Leg length discrepancy
Bibliography
Bale AE, Drum MA, Parry DM, Mulvihil JJ. Familial Sotos syn- drome (cerebral gigantism): craniofacial and psychological characteristics. Am J Med Genet 1985; 20: 613–24
Baujat G, Rio M, Rossignol S, Sanlaville D, Lyonnet S, Le Merrer M, Munnich A, Gicquel C, Cormier-Daire V, Colleaux L.
Paradoxical NSD1 mutations in Beckwith-Wiedemann syndrome and 11p15 anomalies in Sotos syndrome. Am J Hum Genet 2004; 74: 715–20
Butler MG, Meaney FJ, Kittur S, Hersh JH, Hornstein L.
Metacarpophalangeal pattern profile analysis in Sotos syn- drome. Am J Med Genet 1985; 20: 625–9
Cohen MM. Tumors and nontumors in Sotos syndrome. Am J Med Genet 1999; 84: 173–5
Cole TRP, Hughes HE. Sotos syndrome. J Med Genet 1990; 27:
571–6
Cole TRP, Hughes HE. Sotos syndrome: a study of the diagnos- tic criteria and natural history. J Med Genet 1994; 31: 20–32 Kok K, Mosselaar A, Faber H, Dijkhuizen T, Draaijers TG, van der Veen AY, Buys CH, Schrander-Stumpel CT. Breakpoint mapping by FISH in a Sotos patient with a constitutional translocation t(3;6). J Med Genet 1999; 36: 346–7
Kurotaki N, Imaizumi K, Harada N, Masuno M, Kondoh T, Nagai T, Ohashi H, Naritomi K, Tsukahara M, Makita Y, Sugi- moto T, Sonoda T, Hasegawa T, Chinen Y, Tomita Ha HA, Kinoshita A, Mizuguchi T, Yoshiura Ki K, Ohta T, Kishino T, Fukushima Y, Niikawa N, Matsumoto N. Haploinsufficiency of NSD1 causes Sotos syndrome. Nat Genet 2002; 30: 365–6 Mastroiacovo P, Dallapiccola B,Andria G, Camera G, Lungarot- ti MS. Difetti congeniti e sindromi malformative. McGraw- Hill, Milan, 1990
Opitz JM, Weaver DW, Reynolds JF Jr. The syndromes of Sotos and Weaver: reports and review. Am J Med Genet 1998; 79:
294–304
Wit JM. Cerebral gigantism (Sotos syndrome). Compiled data of 22 cases. Eur J Pediatr 1985; 144: 131–40
Sotos Syndrome 878
Sotos Syndrome 879
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Fig. 97.1. Patient 1, age 4 months. Macrocrania, prominent forehead, receding anterior hairline, narrow temples with apparent ocular hypertelorism, anteverted nares, and long philtrum
Fig. 97.2. Patient 2, age 3 months. Macrocephaly, with promi- nent forehead; and steep middle cranial fossa, with posteriorly inclined, small sella turcica
Fig. 97.3 a, b. Patient 2, age 3 months. Note mild thoracic scoliosis and thoracolumbar kyphosis
a b
Sotos Syndrome 880
Fig. 97.4 a–c.Patient 2, age 3 months. Note advanced skeletal maturation relative to child’s chronological age, with well- developed epiphyses at the hips, knees, and tubular bones of the feet. Bone age in hand is about 2 years. (Reprinted, with permission, from Mastroiacovo et al. 1990)
a
c
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