Russell-Silver Syndrome

A genetic disorder characterized by a severe form of asymmetric dwarfism with growth retardation, peculiar facies, and frequent hypoglycemia.

Silver-Russell Dwarfism; Silver Syndrome; Silver-Russell Syndrome.

Rare; more than 150 cases have been described.

Autosomal recessive. Most cases are sporadic. No established mendelian or chromosomal basis, with new dominant mutation or X-linked dominant inheritance possible. Gene map locus at 17q25.

In 1985, Partington proposed an X-linked inheritance for this syndrome, but described children with no asymmetry and a pigmentary anomaly quite different from the café-au-lait spots. This syndrome is sometimes called Russell-Silver X-linked or Partington syndrome, but should not be confused with the true Partington syndrome, which is characterized by the association of mental retardation, X-linked transmission, dystonic movements, ataxia, and seizures.

The two main features are low birth weight dwarfism and lateral asymmetry.

The first feature is extreme intrauterine growth retardation with normal head circumference, sometimes referred as pseudohydrocephalus. The characteristic facial features are craniofacial disproportion, delayed fontanel closure, triangular facies, turned-down mouth corners, and micrognathia. Asymmetry of arms and/or legs causes hemihypertrophy and lateral asymmetry. Fifth finger clinodactyly and syndactyly of toes are observed. The radiology findings are usually fifth finger middle or distal phalangeal hypoplasia, ivory epiphyses, second metacarpal pseudoepiphysis, vertebral abnormalities, absent sacrum, and absent coccyx. Hypoglycemia at birth and even after is common. Café-au-lait spots, precocious sexual development, and cryptorchism are frequent. Cardiac defects can be observed. Gastrointestinal manifestations are now known to be a part of the disease (gastroesophageal reflux, esophagitis, food aversion, and failure to thrive). Susceptibility to malignancies is higher. Normal intelligence is the rule with some delay in the early motor milestones because of the decreased muscle bulk and relatively large head. The children remain thin with a lack of subcutaneous fat. Therapeutic trials with growth hormone have not corrected the growth pattern.

The airway must be carefully assessed (clinical, radiographs). Search for cardiac defect (clinical, echocardiography). Evaluate hypoglycemic risk (clinical, history, glucose level). Search for gastroesophageal reflux (clinical, endoscopy, manometry).

The potential for difficult direct laryngoscopy and tracheal intubation is common because of facial malformations. In case of difficult airway or suspicion of difficulty, it is recommended to maintain spontaneous ventilation until the trachea is secured and lung ventilation confirmed. A laryngeal mask airway and fiberoptic equipment must be available. Pay special attention to the glucose need because of the easily depleted glycogen storages and severe hypoglycemia intraoperatively. Preoperative fasting may be minimal or preoperative glucose infusion realized. Careful intraoperative positioning is needed because of skeletal malformations. Regional anesthesia is not contraindicated but can be difficult to realize as a result of anatomical modifications and may also require intraoperative glucose monitoring because of the suppression of adrenergic response to surgical stress that is induced by these techniques. Rapid induction sequence is needed in cases of gastroesophageal reflux.

Avoid muscle relaxants until airway is secured. Prophylactic antibiotic in cases of cardiopathy. Drugs should be adapted to body area more than to body weight.

Three M Syndrome: Rare inherited disorder characterized by low birth weight, dwarfism, triangular-shaped face, frontal bossing, and dolichocephaly. Other clinical features include clinodactyly, and hypospadias. Skeletal abnormalities include unusually thin diaphyses of the long bones of the arms and legs, abnormally long vertebrae, and distinctive malformations of scapulae.

Floating-Harbor Syndrome (FHS): Characterized by dwarfism, a triangular face, wide downturned mouth with thin lips and large bullous rounded nose. Other clinical features include clinodactyly, brachydactyly, posteriorly rotated ears, and speech and psychomotor development delay. Congenital heart defects have been reported in some cases and consisted of atrial/ventricular septal defects. The original cases were reported at the Boston Floating Hospital and Harbor General Hospital, Torrance, California, hence the name Floating-Harbor syndrome. It is probably inherited as an autosomal dominant.

SHORT Syndrome: An acronym that stands for (S)hort stature, (H)yperextensibility, (O)cular depression, (R)ieger anomaly, and (T)eething delays. Individual affected presents a triangular-shaped face, downturned corners of the mouth, sunken eyes, and Rieger anomaly (gray or white ring in the margin of the cornea) and glaucoma. Other clinical features include clinodactyly, lipoatrophy, dental abnormalities, a high incidence of inguinal hernia. It has been suggested that an autosomal recessive transmission was most probable.

Mulibrey Nanism Syndrome: Based on the acronym “MULIBREY” that stands for (MU)scles, (LI)ver, (BR)ain, and (EY)es. Infants usually have low birth weight and failure to thrive leading to growth delays and dwarfism. Other clinical features include hepatomegaly, craniofacial anomalies, a triangular-shaped face, and hydrocephalus. It might be inherited as an autosomal recessive pattern.