What is Femoral-facial syndrome?

Femoral-Facial Syndrome (FFS) is a rare genetic disorder characterised by underdeveloped thigh bones and distinctive facial features like a small jaw, cleft palate, prominent forehead, small nose, long area between the nose and mouth, and a thin upper lip.¹

Initially called femoral hypoplasia-unusual facies syndrome (FHUFS), more cases revealed additional traits such as arm defects, spine abnormalities, severe femur issues, and problems with the urinary and nervous systems. Despite these physical issues, almost all patients have normal intelligence.¹

The syndrome’s impact on feeding and nutrition can be profound, affecting an individual’s growth, development, and overall quality of life.

Causes

Burn et al. classified FFS into two groups, based on the presence or absence of facial dysmorphism, suggesting that causes could include fetal constraint, maternal diabetes, or unknown factors.⁵ Maternal diabetes has been linked to a higher risk of congenital anomalies such as neural tube defects, heart disease, and skeletal malformations in infants, although the exact role of diabetes in causing FFS remains controversial.⁶

Research has shown that disturbances in glucose metabolism during early development may contribute to FFS. For example, insulin injections in chicken embryos led to limb and facial defects similar to FFS. Uncontrolled glucose levels, rather than exogenous insulin, seem to cause these issues in humans. Studies indicate that abnormal glucose levels can impair cartilage development, suggesting that glucose instability is detrimental during embryonic development.⁶

Although there is a higher occurrence of FFS in infants of diabetic mothers, the overall probability remains low. Experimental studies indicate that hyperglycemia is not the primary cause of diabetic embryopathies, implying other factors like genetic disposition play a role. In a review of 55 FFS cases, 38.2% involved diabetic mothers.⁶ This suggests that while maternal diabetes is a contributing factor, it is not the sole cause of FFS.

Feeding challenges

Anatomical and functional issues

Feeding difficulties in FFS often arise from the syndrome's anatomical and functional challenges. The facial anomalies associated with FFS, such as cleft lip and/or palate, can create significant barriers to effective feeding. Cleft palate, in particular, impairs the ability to form a proper seal around the nipple, making breastfeeding or bottle-feeding problematic. This can lead to insufficient nutrition intake and a higher risk of aspiration, where food or liquids enter the airway instead of the oesophagus.¹

Moreover, individuals with FFS may experience impaired muscle function related to the oral cavity. Weakness or poor coordination of the oral motor muscles can hinder the process of chewing and swallowing. This may result in difficulties transitioning from liquid to solid foods and increase the risk of choking or gagging during meals.¹

Feeding difficulties

The feeding difficulties in FFS are multifaceted. Infants with the syndrome may show signs of inadequate feeding, including slow feeding rates, difficulty maintaining latch, and refusal to eat. These issues can lead to growth delays and inadequate caloric intake. Transitioning to solid foods can be challenging due to difficulties in chewing and managing textures, which may necessitate a prolonged reliance on pureed or soft foods.¹

Strategies for feeding management

To address feeding challenges in FFS, several strategies can be employed:

1. Specialized feeding bottles and nipples: Using bottles with variable flow rates or nipples with soft, squeezable designs can help accommodate the child’s oral motor difficulties
2. Speech and occupational therapy: Therapy can play a crucial role in improving oral motor skills. Speech therapists can work on exercises to enhance sucking, chewing, and swallowing abilities. Occupational therapists can provide guidance on adaptive feeding techniques and appropriate positioning to facilitate safer and more effective feeding
3. Alternative feeding methods: In cases where oral feeding is not feasible, alternative methods such as nasogastric tubes or feeding pumps may be necessary

Nutritional challenges

Nutritional needs and requirements

Individuals with FFS have unique nutritional needs due to their feeding difficulties. Caloric requirements may be higher because of the increased energy expenditure during feeding and potential growth delays. However, there is currently very little evidence to support and no official guidelines have been implicated.

A well-rounded diet that includes adequate amounts of protein, vitamins, and minerals is essential. However, meeting these nutritional needs can be challenging due to difficulties with food intake and digestion.

Common nutritional deficiencies

Due to the feeding difficulties, individuals with FFS are at risk of several nutritional deficiencies. Malnutrition may also be a risk if the child cannot consume enough calories to support growth and development. This can lead to delays in reaching developmental milestones and overall health issues.

Case studies and real-life examples

Cases in adult

A 42-year-old woman with FFS presented to a gastrointestinal clinic with severe dysphagia, food regurgitation, and chronic low energy. Despite a history of heartburn and gastroesophageal reflux disease, her symptoms progressively worsened over two months, and she was diagnosed with marked iron deficiency anaemia. Initially, blood transfusion was not possible due to difficulty in starting an intravenous line, so she was placed on iron supplements.

Upon further investigation, significant gastrointestinal issues were identified: a shortened oesophagus, a severe proximal oesophagal stricture, and Barrett’s oesophagus with invasive oesophagal adenocarcinoma. Her diet was significantly affected; she could no longer tolerate solid foods and had difficulty swallowing thick liquids, leading to nutritional challenges.

Her intake was reduced to small volumes of a thick liquid diet, which still proved difficult to swallow. Despite these difficulties, her hydration was maintained. She experienced frequent regurgitation and a sensation of food getting stuck in her throat.

Tragically, before she could receive further cancer treatment, the patient contracted COVID-19, leading to rapid health deterioration and death from complications related to the virus.²

Cases in children

A 32-year-old mother had a premature baby boy at 33 weeks due to early membrane rupture. The baby had intrauterine growth retardation and a short right femur. At birth, he had respiratory distress and required treatment for hydrocephalus. He was diagnosed with FFS and had various physical anomalies, including short thigh bones, hip dysplasia, short fingers, and distinct facial features. He also had hernias, undescended testicles, and hearing loss in one ear.

The baby and his older sister, who also had developmental delays, both inherited a genetic duplication from their mother, though its role in their conditions is unclear. By 17 months, the baby showed intellectual disabilities, speech and walking delays, poor growth, and difficulty with oral feeding, making it challenging for him to eat properly.³

Another baby girl born at 35 weeks with FFS faced multiple congenital issues, including a cleft palate, small jaw, and underdeveloped lower body. She was given a gastrostomy tube in the NICU to help with feeding due to her cleft palate and jaw issues. This tube ensured she received proper nutrition.

After several surgeries and interventions, she was lost to follow-up for three years. Upon returning, she still relied on the gastrostomy tube for feeding due to continued difficulties with oral intake. Her diet was managed through this tube to ensure adequate nutrition despite her feeding challenges.⁴

Future directions and research

Current research on femoral-facial syndrome and feeding

Ongoing research is essential for understanding Femoral-Facial Syndrome and its feeding challenges. Studies are exploring the genetic and molecular underpinnings of the syndrome, which may lead to new insights and management strategies. Research into innovative feeding techniques and therapies is also critical for improving care.

Emerging therapies and interventions

Emerging therapies, including advanced feeding technologies and personalized nutrition approaches, offer promising solutions for managing feeding challenges in FFS. Advances in medical technology may lead to new tools and techniques for improving feeding efficiency and addressing specific nutritional needs.

Importance of continued research for better management

Continued research is vital for enhancing our understanding of Femoral-Facial Syndrome and developing effective management strategies. Collaboration between researchers, healthcare professionals, and affected families can drive progress and improve outcomes for individuals with FFS.

FAQs

What role does maternal diet play in the development of Femoral-Facial Syndrome?

Maternal diet influences Femoral-Facial Syndrome primarily through its impact on blood glucose levels. Poorly controlled diabetes, often due to a high-sugar diet, increases the risk of congenital anomalies like FFS.

How does the clinical presentation of FFS change as patients age?

As patients with Femoral-Facial Syndrome (FFS) age, some facial features like micrognathia and cleft palate may become less pronounced, potentially making the syndrome harder to diagnose in adulthood. However, limb deformities and mobility challenges often persist or worsen over time.

Can a high-sugar diet during pregnancy increase the risk of FFS in the child?

Poor glucose control is linked to disruptions in fetal development, which may contribute to conditions like FFS.

Summary

Feeding and nutritional challenges in FFS require a comprehensive approach to ensure optimal growth and development. A multidisciplinary team, including paediatricians, dietitians, and therapists, is essential for addressing these challenges and providing individualised care. By employing tailored feeding strategies, addressing nutritional deficiencies, and staying informed about emerging research, caregivers and healthcare professionals can work together to enhance the quality of life for individuals with FFS.