Simpson-Golabi-Behmel syndrome

Simpson-Golabi-Behmel syndrome is a rare X-linked recessive disorder of pre- and postnatal overgrowth syndrome represented by mild to severe intellectual disability ^3,7, anomalies of the musculoskeletal system, cardiovascular system, central nervous system, renal and gastrointestinal tract were observed ¹¹.

Clinical presentation

Simpson-Golabi-Behmel syndrome is characterized by:

• polyhydramnios 
• neonatal recurrent hypoglycemia ⁶ 
• facial deformities, including cleft lip and palate ⁹, macrostomia, macroglossia and dental malocclusion ¹² 
• hepatosplenomegaly
• multicystic dysplasia of kidneys
• malrotation of bowel loops
• Meckel diverticulum
• congenital heart defects
• supernumerary nipples
• umbilical and diaphragmatic hernias ^1,3,5.
• skeletal manifestations, such as congenital C2–C3 vertebral fusion and cervical ribs ⁴.

Like other overgrowth disorders, there is an increased risk of Wilms tumor ¹⁸, adrenal neuroblastoma ¹⁷, gonadoblastomas, hepatoblastomas ¹⁹ and acute lymphoblastic leukemia ^2,3,8.

Pathology

Simpson-Golabi-Behmel syndrome is caused by loss of function mutation in the (glypican-3) CPC3 gene ⁸, and in some cases CPC4, that eventually leads to overgrowth disorder and multiple malignancies ^2,5,7.

Differential diagnosis

Differential diagnosis includes ^1,5,7:

• Beckwith-Wiedemann syndrome 
• Fragile X syndrome 
• Perlman syndrome
• Sotos syndrome