Overview

In recent years, significant progress preventing and treating developmental abnormalities. This shift in our understanding of developmental abnormalities has enabled greater management and prevention. Despite these advances, developmental abnormalities continue to be a major source of morbidity worldwide.

Pfeiffer syndrome is a rare autosomal dominant genetic disorder characterised by craniosynostosis, broad and deviated thumbs and huge toes, and partial syndactyly in the hands and feet.
Hydrocephaly can occasionally be seen in conjunction with significant ocular proptosis, ankylosed elbows, aberrant viscera, and delayed development.¹

Apert syndrome is a rare congenital genetic disorder, also known as acrocephalosyndactyly, that involves the early fusion of the skull bones, face, and limbs. It is commonly associated with craniosynostosis, midface hypoplasia, and syndactyly.⁵

Pfeiffer syndrome and Apert syndrome share certain similarities; however, the two conditions are clinically and genetically unique.

Introduction

Pfeiffer syndrome 

Pfeiffer syndrome is an uncommon autosomal dominant condition characterised by craniosynostosis, large thumbs and toes, and partial syndactyly of the hands and feet.¹

Pfeiffer syndrome is categorised into three clinical subgroups. Type 1, known as "classic" Pfeiffer syndrome, presents with mild symptoms such as brachycephaly, midface hypoplasia, and deformities of the fingers and toes; it is associated with normal intelligence and a fair prognosis. Type 2 presents as a cloverleaf skull, severe proptosis, finger and toe deformities, elbow ankylosis or synostosis, developmental delay, and neurological problems. Type 3 is similar to type 2, but without the cloverleaf skull.³

Characteristics

The main diagnostic features of Pfeiffer syndrome include craniosynostosis, short, broad thumbs, and large toes. Patients have premature fusion of the coronal and lambdoid sutures, and occasionally of the sagittal sutures, resulting in an irregular skull form.

The facial features include a disproportionately large head and flat occiput, a big, high forehead, an underdeveloped midface with receded cheekbones (midfacial hypoplasia), a short nose with a low nasal bridge, and widely spaced eyes (ocular hypertelorism).¹

Patients with very thin orbits frequently have eye prominence (ocular proptosis). The thumbs and big toes are small but wide. The thumbs and great toes are typically separated from the other digits, and the second and third fingers and toes have webbing (syndactyly).

Additional abnormalities may include intellectual disability, aqueduct stenosis with resulting hydrocephaly, cerebellar and brain stem herniation, low-set ears, external auditory canal stenosis or atresia, recurrent ear infections, and, infrequently, internal anomalies such as hydronephrosis, pelvic kidneys, and hypoplastic gallbladder.³

Visual abnormalities might be primary (caused by proptosis) or secondary (caused by increased intracranial pressure). Individuals with Pfeiffer syndrome may experience upper airway obstruction due to midface hypoplasia and subsequent nasal obstruction; tracheal anomalies have been occasionally documented.

The three subtypes of Pfeiffer syndrome are:

Type 1:  Brachycephaly, midface hypoplasia, and finger and toe abnormalities. It usually produces positive results and is linked to appropriate neurological and intellectual development.¹

In most cases, individuals will have normal intelligence.²

Type 2: Cloverleaf skull, extreme proptosis, finger and toes abnormalities, elbow ankylosis or synostosis, developmental delay, and neurological complications. Limited brain growth and significant vision problems can result from the cloverleaf skull's strong proptosis ^1.,2

Type 3: Hallmarks include severe ocular proptosis, shallow orbits, and marked shortness of the anterior cranial base. Patients are neurologically compromised, do poorly, and tend to die early.² This type is similar to type 2 but without the cloverleaf skull. The absence of a cloverleaf skull in type 3 can make it difficult to diagnose.¹

Apert syndrome 

In 1906, Eugene Apert published the first description of Apert syndrome. The three conditions he described were maxillary, syndactyly, and craniosynostosis. Although autosomal dominant inheritance is known to occur, most cases are sporadic. It is hypothesised that the occasional incidences are linked to advanced paternal age. Apert syndrome occurs in about 1 in 50,000 babies.⁵

Clinical features

The infant Apert skull has premature coronal suture fusion and a large calvarial midline defect that begins at the glabella and finishes at the posterior fontanelle. Many of those affected have agenesis of the corpus callosum, increasing hydrocephalus, and hippocampal abnormalities.

Early surgical intervention for craniosynostosis is critical for achieving normal growth. The ocular orbits are shallow, and the concomitant exophthalmia can lead to blindness. The condition may present with ocular signs such as hypertelorism and exophthalmia.⁵

Patients with Apert also have a distinctive oral cavity. Among the results is a decrease in maxillary size, especially in the anterior-posterior direction. Teeth crowding may result from this reduction. The majority of instances have either a bifid uvula or a cleft palate. Dental abnormalities include impacted teeth, thick gingiva, ectopic eruption, delayed eruption, and the presence of extra teeth ⁵

Apert syndrome can cause hyperhidrosis, brittle nails, and synonychia. This combination often results in candidal infection and colonisation. Severe acne that only responds to isotretinoin has also been linked to Apert syndrome.⁶

Other reported findings include hypopigmentation, hyperkeratosis, and severe skin wrinkling on the forehead, shoulders, elbows, and knuckles.

Apert syndrome is distinguished by multisuture craniosynostosis, midface retrusion, and syndactyly of the hands with fusion of the second to fourth nails. Almost every affected person has coronal craniosynostosis, and the majority of them also have sagittal and lambdoid sutures involved.

In Apert syndrome, the midface is underdeveloped and retruded. Some individuals have a cleft palate, and the middle three digits are always fused, although the thumb and fifth finger may be affected.. Common issues include feeding problems, dental deformities, hearing loss, hyperhidrosis, and progressive synostosis of several bones, including those in the cranium, hands, feet, carpus, tarsus, and cervical vertebrae.⁶

Multilevel airway obstruction may occur due to nasal channel restriction, tongue-based airway obstruction, and/or tracheal abnormalities. The majority of people have nonprogressive ventriculomegaly, with only a small proportion having actual hydrocephalus.

The majority of people with Apert syndrome have normal intelligence or mild intellectual disability; however, some people have moderate-to-severe intellectual disabilities. A small number of those affected have structural heart abnormalities, genuine gastrointestinal malformations, and defects in the genitourinary system. 

Key differences

Conclusion

Pfeiffer syndrome and Apert-type acrocephalosyndactyly share some similarities; however, Pfeiffer syndrome is less severe.. Pfeiffer syndrome could be considered a mild form of Apert-type acrocephalosyndactyly.

Apert syndrome features the fusion of the soft tissues of the second, third, and fourth digits; this manifestation is similar to Pfeier syndrome, but in Apert syndrome, there is often fusion of both bones and soft tissues.⁴

According to Cohen and Kreiborg, no transition between Apert and Pfeiffer has been observed within families, despite the variability expressed in the disorders. This suggests that the two disorders are nosologically and genetically distinct.