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Russell-Silver syndrome

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Russell-Silver syndrome
Sue Ann Wee MD
Dermatology Online Journal 13 (1): 16

New York University Department of Dermatology

Abstract

A 27-year-old woman presented with congenital growth retardation, facial dysmorphism, and limb asymmetry. Additional clinical findings lead to a diagnosis of Russell-Silver syndrome with sporadic occurrence. Treatment requires a multidisciplinary approach. Clinical features and treatment options are reviewed.



Clinical synopsis

A 27-year-old woman with a history of congenital short stature and limb asymmetry presented to the Charles C. Harris Skin and Cancer Pavilion in August 2005 for acne conglobata. She had suffered poor intrauterine and postnatal growth, with low birth weight, feeding difficulties, short stature, and limb asymmetry. She has had a poor appetite since childhood. Despite difficulties in school, she attended public high school and graduated from college. She notes recent problems with concentration, word-finding, and slurred speech. She also notes a 6-month history of exertional chest pain, which is currently being evaluated by her primary care physician. She denies that any other family members have the same condition.

A well-appearing, thin, short woman has a normal head circumference, with a broad forehead, prominent nasal bridge, triangular facies, low-set prominent ears, micrognathia, and crowded teeth. The third and fourth phalanges of the hands showed swan-neck deformities, and the left fifth phalanx showed clinodactyly. Asymmetry of the hands, phalanges, and lower extremities were noted, with hemihypertrophy of the left lower extremity. Poorly-demarcated, subcutaneous masses were present on the anterior aspects of the thighs. No cafe-au-lait macules were noted.


Figure 1Figure 2

A complete blood count, testosterone, and dihydroepiandrosterone sulfate were normal. Chromosomal and karyotype analyses were normal.


Comment

Russell-Silver syndrome (RSS) is a congenital disorder whose primary features are growth retardation, short stature, facial dysmorphism, and limb asymmetry [1, 2].

The incidence of the disorder is one in approximately 100,000 live births. There is no sex or racial predilection. Most cases appear to be sporadic, but recessive, dominant, and x-linked modes of inheritance have been documented [3, 4, 5]. Maternal uniparental disomy of chromosome 7 (matUPD7) has been found in approximately 10 percent of patients [6, 7]. However, studies of multiple candidate genes have not detected the precise defect.

Common clinical features include poor intrauterine and postnatal growth, feeding difficulties, developmental delays, late closure of the anterior fontanel, triangular facies, frontal bossing, blue sclerae, down-curving mouth corners, micrognathia, limb asymmetry, and fifth-finger clinodactyly. [1,2] Cafe-au-lait macules are the most common cutaneous manifestations; however, a sharply-demarcated, unilateral, hypopigmented patch on the left chest and abdomen was reported in a 13-month-old boy with RSS [8]. Acne has not been reported as a specific finding in RSS. Other features include learning and motor-coordination difficulties, genitourinary defects, ear anomalies, high-pitched voice, and fasting hypoglycemia. Rare findings include cardiac defects and underlying malignant conditions [9, 10].

There are no laboratory or radiographic studies that are pathognomonic, and the diagnosis is based on the constellation of clinical findings. Genetic tests should aim to detect chromosomal rearrangements and matUPD7. Radiographic findings are confirmatory and include delayed maturation, clinodactyly, fifth middle or distal phalangeal hypoplasia, ivory epiphyses, and a second metacarpal pseudoepiphysis [11].

Clinical genetic, gastroenterologic, nutritional, and endocrinologic consultations are important for diagnosis and for directing multidisplinary supportive care. Nutrition, growth hormone, and luteinizing hormone-releasing hormone may help to optimize growth and development. Enteral feedings may be necessary for individuals who cannot tolerate oral feedings. Shoe lifts and corrective surgeries are options for limb-length asymmetry. Early developmental intervention programs, speech and physical therapy, and RSS support groups may improve the overall quality of life.

Most RSS patients have a favorable prognosis. Motor function, facial dysmorphism, and height improve as the child becomes an adult.

References

1. Silver HK, et al. Syndrome of congenital hemihypertrophy, shortness of stature and elevated urinary gonadotrophins. Pediatrics 1953; 12: 368

2. Russell A. A syndrome of "intra-uterine" dwarfism recognizable at birth with craniofacial dysostosis, disproportionately short arms and other anomalies. Proc R Soc Med 1954; 47: 1040

3. Duncan PA, et al. Three-generation dominant transmission of the Silver-Russell syndrome. Am J Med Genet 1990; 35: 245

4. Al-Fifi S, et al. Autosomal dominant Russell-Silver syndrome. Am J Med Genet 1996; 61: 96

5. Ounap K, et al. Two sisters with a Silver-Russell phenotype. Am J Med Genet 2004; 131: 301

6. Kotzot D, et al. Uniparental disomy 7 in Silver-Russell syndrome and primordial growth retardation. Hum Mol Genet 1995; 4: 583

7. Eggermann T, et al. Molecular studies in 37 Silver-Russell syndrome patients: frequency and etiology of uniparental disomy. Hum Genet 1997; 100: 415

8. Perkins RM, Hoang-Xuan MA. The Russell-Silver Syndrome: a case report and brief review of the literature. Pediatric Dermatology 2002;19:546

9. Cole RB, Levin SE. Congenital heart disease associated with the Russell-Silver syndrome. S Afr Med J 1973; 47:989

10. Bruckheimer E, Abrahamov A. Russell-Silver syndrome and Wilms tumor. J Pediatr 1993;122:165

11. Herman TE, Crawford JD, Cleveland RH, et al. Hand radiographs in Russell-Silver syndrome. Pediatrics 1987; 79:743

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