Silver-Russell syndrome due to maternal uniparental disomy of chromosome 11

Silver-Russell syndrome due to maternal uniparental disomy of chromosome 11 (matUPD11) is a rare genetic imprinting disorder and one of the recognized molecular subtypes of Silver-Russell syndrome (SRS). In this condition, a child inherits both copies of chromosome 11 (or a segment of it) from the mother, rather than one from each parent. This leads to loss of expression of paternally expressed imprinted genes at the 11p15.5 region, particularly IGF2 (insulin-like growth factor 2), which plays a critical role in fetal and postnatal growth. The result is a clinical picture consistent with Silver-Russell syndrome, characterized by severe intrauterine growth restriction (IUGR), low birth weight, postnatal growth failure, relative macrocephaly at birth, a triangular facial appearance, prominent forehead, body asymmetry (limb length discrepancy), and feeding difficulties in early life. The condition affects multiple body systems. Growth is profoundly impaired, and children typically present with short stature that persists without intervention. Musculoskeletal features include body asymmetry and fifth finger clinodactyly. Gastrointestinal issues such as poor appetite, gastroesophageal reflux, and feeding difficulties are common in infancy and early childhood, sometimes requiring nutritional support. Hypoglycemia may occur, particularly in early life, due to reduced fat stores and poor feeding. Cognitive development is generally normal, though some children may experience mild learning difficulties or speech delay. Management of Silver-Russell syndrome due to matUPD11 is multidisciplinary. Growth hormone therapy is a well-established treatment that can improve final adult height and body composition, and is recommended by international consensus guidelines. Nutritional support, monitoring for hypoglycemia, and management of feeding difficulties are essential in early life. Orthopedic evaluation may be needed for significant limb length discrepancy. Long-term follow-up addresses potential metabolic complications and psychosocial support. MatUPD11 accounts for a small proportion of molecularly confirmed SRS cases, with the majority being caused by hypomethylation of the H19/IGF2 imprinting control region at 11p15.5 or maternal uniparental disomy of chromosome 7.

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