Frank-Ter Haar syndrome

Frank-Ter Haar syndrome is a very rare inherited condition that affects several body systems, especially the eyes, skeleton, heart, and facial development. It is caused by changes in the SH3PXD2B gene, which disrupt normal formation of connective tissue and bone. Signs are usually apparent at birth or in early infancy and can include unusually large eyes, characteristic facial features, and skeletal differences. The condition affects fewer than one in one million people worldwide. Severity and symptoms vary widely between individuals.

The clinical picture of Frank-Ter Haar syndrome spans multiple organ systems. Ocular features are often the first to draw medical attention. Many babies have megalocornea and buphthalmos, giving the appearance of very large, prominent eyes. Proptosis, or forward displacement of the eyes, is consistently reported, and some children develop vision problems related to the enlarged globes. Skeletal findings include wide anterior fontanels, kyphoscoliosis, bilateral clubfeet, and a prominent coccyx. Over time, these bone differences can contribute to posture concerns and limited mobility. Characteristic facial traits include a broad nasal tip, depressed nasal bridge, full cheeks, thin upper lip, and micrognathia. Low-set ears and redundant neck skin are also common. Cardiac involvement arises from structural defects such as secundum atrial septal defect or a patent foramen ovale, both present from birth. Ongoing monitoring is important because mild heart defects can progress or lead to complications if unrecognized. Neurologically, hypotonia, motor delay, and structural brain findings like hypoplasia of the corpus callosum or an enlarged cisterna magna may contribute to delayed developmental milestones. Café-au-lait skin spots and acne represent dermatologic manifestations. Not all individuals experience every feature, and the intensity of each symptom can differ considerably.

Frank-Ter Haar syndrome results from pathogenic variants in the SH3PXD2B gene. This gene provides instructions for a protein that helps cells shape the skeleton and connective tissues; when the protein is faulty, normal bone, eye, and heart development is disrupted. The condition is inherited in an autosomal recessive pattern, meaning a child must receive one altered copy of SH3PXD2B from each parent to be affected. Parents who each carry one altered copy are typically healthy but have a 25 percent chance with every pregnancy of having an affected child. Because the disorder is very rare, it is more likely to appear when parents share a common ancestor, since they may unknowingly carry the same rare variant. Carrier testing may be particularly relevant for families with shared ancestry, and genetic counseling is recommended for family planning.

Currently, management focuses on supportive care and symptom-based interventions tailored to each individual, delivered through a multidisciplinary team. Early involvement of ophthalmology can address elevated eye pressure or vision changes, and orthopedic specialists manage spinal curvature or clubfeet with bracing or surgery when needed. Cardiology follow-up monitors septal defects to determine whether surgical repair is required. Physical and occupational therapists support motor development, while developmental specialists guide individualized education plans. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Families should discuss specific monitoring schedules with their care team and revisit them as new symptoms emerge. Genetic counseling offers guidance on carrier testing for relatives and informs future pregnancy decisions.

Outcomes for people with Frank-Ter Haar syndrome depend on the number and severity of organ systems involved as well as access to specialized care. Some children achieve good functional mobility and learning progress with early therapy, while others face significant challenges from cardiac or skeletal complications. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with this condition and with genetic counselors who can guide future planning.