The following description of the clinical manifestations is based on a comprehensive review of the literature and personal observations of the moderators (unpublished data).
Hemoglobin
A key manifestation of this condition is the persistence of fetal haemoglobin, most commonly identified by hemoglobin electrophoresis or HPLC (High Performance Liquid Chromatography). While fetal hemoglobin (HbF) physiologically decreases after birth within the first 12 months of life, HbF level tend to persist in affected individuals. Persistence of HbF is thought to be asymptomatic.
Growth parameters
Intrauterine growth retardation (IUGR) and postnatal growth delay can be present, but more than half of the patients have normal growth parameters. Microcephaly can be present (approximately half).
Neurological features
Individuals with intellectual disability with persistence of fetal hemoglobin syndrome present with developmental delay and ID. The level of ID is variable, and can range from mild to severe. Speech delay is always present. Neonatal hypotonia is seen in the majority of patients, and may result in delayed motor development. Autism spectrum disorder has been described in a subset of patients. Others have been identified with variable behavioural problems. Structural anomalies of the central nervous system can be present, including corpus callosum hypoplasia and hypoplasia of the cerebellar vermis. Seizures have been reported.
Craniofacial features
Individuals with intellectual disability with persistence of fetal hemoglobin syndrome have a distinctive facial gestalt with a flat midface and everted lower lip. External ear dysplasia may also be present. However, common facial features that would define a recognisable syndrome in the absence of supporting HbF persistence have been not found.
Visual impairment
Strabismus is a common manifestation.
Other physical features
Joint hypermobility is a common feature. Other features identified in single patients include scoliosis, valgus foot deformity and congenital hip dislocation.