Introduction

If you’re looking for clear, reliable answers about De Barsy syndrome, you’re in the right place. Understanding this genetic disorder is crucial for improving patient outcomes and guiding family support. Although it is uncommon, it can present with distinctive clinical features that require an informed medical approach, so awareness and accurate diagnosis are essential in clinical practice.

De Barsy syndrome is a rare, autosomal recessive disorder characterised by a combination of progeroid features and cutis laxa as well as developmental delay.¹ Despite its rarity, understanding this syndrome is crucial, with early identification enabling timely intervention, supporting genetic counselling and improving the quality of life of affected individuals. This article outlines key clinical features, diagnostic criteria and a structured clinical approach to managing this syndrome.

How does this syndrome occur?

Mutations either tend to be on the PYCR1 or ALDH18A1 genes in an autosomal recessive manner. The ALDH18A1 gene encodes an adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADP) dependent mitochondrial enzyme. This protein is crucial in the synthesis of proline, ornithine, and arginine. However, mutations in this gene can therefore result in low proline levels, leading to a reduced production of collagen and elastin. This explains why patients experience connective tissue weakness, which is detrimental to infantile growth. Limited proline availability can also result in reduced antioxidant protection in the central nervous system, leading to neurocognitive impairment.²

Clinical presentations of this syndrome

De Barsy syndrome is typically caused by underdevelopment of the skin, resulting in loose, sagging, and inelastic skin and, consequently, an aged appearance. This is known as cutis laxa. The skin may also be thin with veins being easily visible, but this is rare.

Infants with this syndrome have distinct clinical facial features, including wide-spaced eyes, dysplastic ears, and an unusually prominent forehead.

Many musculoskeletal and growth abnormalities, such as frequent dislocations, osteoporosis and low bone mineral density, are found. Developmental dysplasia of the hip and severe foot deformities are also observed. This can severely affect the growth of patients, viz., a height that is below what is expected for their age and gender.

Mental retardation is also very common, with patients never learning to speak, but they may also have hyperreflexia, where their reflexes are stronger than usual. However, for some, this is not a problem, with intelligence only being mildly impaired.³ Additionally, there are neurological manifestations such as involuntary seizures and hypotonia, which can develop as they grow older.

Abnormalities related to vision are another common type of issue associated with De Barsy Syndrome. These include clouding of the corneas of the eyes or in the lenses of the eyes, nystagmus, as well as eyes not lining up in the same direction, such as crossed eyes.

How is De Barsy syndrome diagnosed?

A detailed patient history and several tests are used to diagnose this syndrome.

Imaging may reveal structural brain abnormalities, delayed bone maturation and skeletal abnormalities such as reduced bone density.

Biopsies of the affected skin can reveal changes in elastic fibres. Gene expression studies show a significant decrease in elastic mRNA levels in fibroblasts, which could be due to impaired transcription or increased degradation. Reduction of collagen mRNA was also seen, explaining the symptoms of poor growth in patients.⁴

Molecular genetic testing can also be used to detect mutations in specific genes, which is essential in cases with overlapping features with other connective tissue disorders and in cases with atypical presentations.

The syndrome shares features with other cutis laxa syndromes, such as autosomal recessive cutis laxa, Hutchinson-Gilford progeria syndrome, and Ehlers-Danlos syndrome.

Thus, a clear and accurate diagnostic approach is essential for accurate identification and management of De Barsy syndrome.

Management and treatment

There is currently no cure for this syndrome; thus, management mainly focuses on multidisciplinary care aimed at improving quality of life. Treatment of this syndrome depends on the symptoms each individual may have and may require care from many specialists, all planning an effective plan for the child’s treatment.

For example, regular eye examinations would be needed for corneal clouding or nystagmus. Dermatologists would be needed to manage cutis laxa, as well as physiotherapists supporting joint hypermobility, delayed motor milestones and musculoskeletal abnormalities. Genetic counselling for families may also be an option, such as prenatal diagnosis in future pregnancies.

Early intervention programmes such as speech and occupational therapy would be necessary in addressing delays, as well as the use of anticonvulsants in managing seizures. 

Regular follow-ups are crucial to monitor disease progression and adjust plans as needed. This may include neurological assessments, vision checks, and lab investigations to assess metabolic abnormalities.

FAQs

What is the prognosis of this disease?

There are variable outcomes. Some die in early childhood due to recurrent infections and severe neurological dysfunctions. However, those diagnosed with PYCR1 mutations show good improvement of the progeroid features.

What should affected individuals avoid?

Environmental triggers can worsen cutis laxa and other symptoms, and should be avoided. For example, sunbathing damages skin.

Does it mainly affect males or females more?

It can affect males and females equally.

How many cases have been reported?

Fewer than 50 in the medical literature. Because it is difficult to diagnose, determining the accurate number in the general population is challenging.

Summary

De Barsy syndrome is a rare, autosomal recessive disorder characterised by progeroid facial features, cutis laxa, developmental delays and multisystem involvement. Diagnosis is mainly clinical with imaging, and is confirmed through genetic testing by identifying mutations in PYCR1, ALDH18A1. Due to overlapping features with other connective tissue disorders, accurate diagnosis is essential for managing this syndrome. While there is no cure, management is multidisciplinary and focuses on symptom relief, developmental support, and long-term monitoring. Therefore, early diagnosis and intervention can improve quality of life and enable appropriate genetic counselling for affected families, making awareness and clinical recognition critically important.