Catel–Manzke syndrome

Overview

Catel–Manzke syndrome is a rare congenital disorder primarily characterized by a combination of craniofacial abnormalities and skeletal malformations. The most notable features include Pierre Robin sequence (a triad of cleft palate, micrognathia, and glossoptosis) and abnormal positioning of the index fingers due to extra bone formations. First described by Catel and later expanded by Manzke, the syndrome is considered a distinct condition, though its features may overlap with other genetic disorders. It usually presents at birth and may require multidisciplinary care.

Causes

Catel–Manzke syndrome is caused by mutations in the TBR1 or TBR1-related regulatory genes in some cases, though the exact genetic basis is still being studied. More recently, mutations in the TGDS gene (encoding TDP-glucose 4,6-dehydratase) have been identified in multiple affected individuals. The syndrome is typically inherited in an autosomal recessive manner, meaning that both copies of the gene must be mutated for the disorder to manifest. Carrier parents typically do not show symptoms.

Symptoms

The symptoms of Catel–Manzke syndrome affect the craniofacial region, limbs, and sometimes other organ systems. Common features include:

• Pierre Robin sequence: Micrognathia (small lower jaw), cleft palate, and tongue displacement (glossoptosis), which can lead to breathing and feeding difficulties

• Index finger abnormalities: Bilateral hyperphalangy or duplication of bones in the index fingers, causing them to angle toward the thumb (clinodactyly)

• Facial dysmorphism: Including a broad nasal bridge, high-arched palate, and prominent eyes

• Feeding difficulties: Often due to cleft palate and jaw abnormalities

• Failure to thrive: In infancy due to feeding and respiratory issues

• Occasional developmental delay

Less commonly, cardiac or other organ anomalies may be present, but the core features remain craniofacial and skeletal.

Diagnosis

Diagnosis of Catel–Manzke syndrome is based on clinical evaluation and confirmed through genetic testing. Steps include:

• Physical examination: Noting the presence of Pierre Robin sequence and hand anomalies

• Radiographic imaging: X-rays of the hands to visualize extra or malformed phalangeal bones

• Genetic testing: Identification of mutations in the TGDS gene or other associated genes confirms the diagnosis

• Feeding and respiratory assessment: Especially in newborns with airway or swallowing issues

• Additional evaluations: Echocardiogram, hearing test, and developmental screening as needed

Treatment

Treatment for Catel–Manzke syndrome is supportive and symptom-based, focusing on the individual’s specific needs. A multidisciplinary team approach is often required. Management may include:

• Feeding support: Specialized feeding techniques, nasogastric tubes, or gastrostomy in severe cases

• Surgical intervention: Repair of cleft palate and correction of jaw abnormalities if necessary

• Orthopedic care: For hand deformities, which may require surgical correction or physical therapy

• Airway management: In cases of severe glossoptosis or breathing difficulty, interventions such as tongue-lip adhesion or tracheostomy may be considered

• Speech and developmental therapy: To address potential delays or articulation issues

• Regular follow-up: With genetics, ENT, orthodontics, and pediatrics for ongoing care

Prognosis

The prognosis for individuals with Catel–Manzke syndrome varies depending on the severity of symptoms. With early diagnosis and appropriate medical and surgical interventions, many affected children can achieve normal or near-normal development. Feeding and breathing problems in infancy are the most pressing concerns and can improve with proper management. Lifelong monitoring may be required, but most individuals do not experience life-threatening complications. Genetic counseling is recommended for families, particularly in cases of confirmed TGDS mutations.