Introduction

Living with a rare genetic disorder that does not have a definite cure must be difficult, not only for the affected individuals but also for their families. Catel-Manzke syndrome is one of the rare genetic disorders that can be challenging.¹ According to the National Institutes of Health, there are fewer than 1,000 people in the U.S. living with this condition. This disorder mainly affects the bones, particularly the ones on the face and hands, with diagnosis often made at birth due to its distinctive features.¹ In this article, we will focus on the characteristic facial features of Catel-Manzke syndrome, as well as explain what the disorder is, the other symptoms, and the challenges that this disorder may bring. 

What is catel-manzke syndrome?

Catel-Manzke syndrome is a rare disorder associated with alterations (mutations) to the TGDS (dTDP-d-glucose 4,6-dehydratase) gene.² This gene gives instructions to make proteins that are involved in the breakdown of a variety of compounds in the body, ³ and mutations to this gene may cause the final protein to be inefficient. This disorder is a genetic trait inherited from two carrier parents. Doctors may suspect the presence of Catel-Manzke syndrome before birth (prenatal). The prenatal images created by ultrasound may reveal abnormalities in the developing baby that are associated with this disorder, indicating the presence, but it is mostly diagnosed at birth, with the infant exhibiting physical characteristics of the disorder.¹ 

What are the symptoms? 

The most common and distinctive symptoms observed with Catel-Manzke syndrome are the presence of abnormal fingers, unusual facial features, and developmental delays.^1,4 Hyperphalangy of the index fingers and fifth finger clinodactyl are the common abnormalities seen with Catel-Manzke syndrome.⁴ Hyperphalangy can be described as the presence of an extra, irregular-shaped bone, located in the first bone of the index finger, resulting in bending of the finger towards the thumb.^1,2,5 Fifth finger clinodactyly can be defined as the curving of the little finger.⁴ 

Also, characterised by Pierre Robin sequence, this disorder has a clear image of symptoms but lacks a complete understanding.²  Pierre Robin sequence can be defined as the combination of three features: micrognathia, glossoptosis and blocked airway.⁶ These medical terms may sound complicated and even difficult to read, but they will be discussed in detail later in this article. Babies with Pierre Robin sequence may have difficulties in breathing and feeding due to these abnormalities.⁷  

Some children may experience learning and speech delays, but the majority remain unaffected.¹ Children with this syndrome frequently suffer from chronic otitis media, which is the infection and swelling of the middle ear. Additionally, as they grow up, they might experience joint stiffness, joint hypermobility, scoliosis (sideways curvature of the spine), and short stature.⁸ Some infants with this syndrome may have abnormalities in the structure of their hearts, most commonly a condition known as “ a hole in the heart”.¹ 

What are the treatment options?

Treatment options revolve around the therapies that can be provided for the symptoms of this disorder for supportive purposes. Lying the infant on their stomach and monitoring breathing can be recommended for those who are struggling with respiratory and feeding difficulties. In severe cases of airway blockage, a tube can be inserted through an opening in the neck. Medications can be helpful for heart-related symptoms, but surgical procedures can be considered if required.¹ 

Providing support at an early age with special services like speech and physical therapies would ensure that the affected child will reach his/her potential.¹ Psychological support for the entire family might be essential to ensure your well-being throughout this time.

Key facial features to recognise

It must be scary, knowing your child will look different in this tough world, maybe not being able to fit in easily, or a life full of challenges with a disorder not fully understood. Accepting and familiarising yourself with the disorder may help in supporting your child with the challenges he/she might be facing. If your child is affected by Catel-Manzke syndrome, you might observe the following facial features:

Micrognathia (mandibular hypoplasia)

Micrognathia is a medical term used to define the condition in which babies are born with an abnormally small and underdeveloped lower jawbone, mandible.⁹ There are several genetic conditions associated with micrognathia, one of them being Catel-Manzke syndrome.¹ 

Micrognathia can be diagnosed before birth using an ultrasound by examining anatomical ratios or facial angles of the face.¹⁰ Babies with this condition are born with an abnormally developed, smaller mandible, and in its severe form, it can lead to functional limitations such as feeding and breathing difficulties.^1,11 Corrective and reconstructive surgical procedures may be suggested for those with delayed growth due to these limitations.¹¹ A Feeding tube can be inserted to support the development of the infant.

Glossoptosis 

Glossoptosis is a condition where the base of the tongue is placed unusually far back in the mouth. It is frequently associated with micrognathia. An unusual, smaller jaw formation may cause the base of the tongue to be positioned abnormally. Glossoptosis can cause obstruction of the airway and difficulty in breathing.¹² A breathing tube can be inserted if required in fatal conditions.

Cleft or high-arched palate

A cleft palate is a condition that occurs when the roof of the mouth doesn't fully close before birth.¹ It is one of the most common birth defects,¹³ and might affect speech and feeding. A cleft palate might be present in children born with Catel-Manzke syndrome; it's often seen but not always present.¹

Upslanted palpebral fissures

Upslanted palpebral fissures are a type of facial dysmorphology (facial anomalies linked to genetic syndromes) and can be described as the eyelids tilting upwards, falling more than two standard deviations above the typical range, giving a characteristic facial profile.¹⁴ Outer corners of the eyes are angled higher than the inner corners, giving a distinctive facial appearance. Upslanted palpebral fissures can be associated with Catel-Manzke syndrome.^5,14

Highly arched eyebrows

Eyebrows may be shaped like a semicircle or an inverted-U with an increased arch in the middle.⁸

Prominent nasal bridge

If your child is dealing with Catel-Manzke syndrome, he/she might have narrow nostrils with a tubular-appearing nose and a high or broad nasal bridge.^1,2

Low-set or abnormally shaped ears

Children with Catel-Menzke syndrome may have ears positioned lower than usual and rotated towards the back of the head, or might have an unusual shape.^1,8 

Full cheeks

More pronounced and round cheeks might be present with Catel-Manzke syndrome.^1,8 This feature may be seen as attractive by modern beauty standards, and fortunately, it doesn’t cause any functional problems.

Iris coloboma

When there is a gap or missing portion in the coloured part of the eye, it is called iris coloboma, giving the pupil a cat-eye or keyhole shape, and can be associated with Catel-Manzke syndrome.¹ This can give your child a distinctive appearance. Coloboma often has no symptoms but may cause vision loss and sensitivity to light. Surgeries or coloured contact lenses are available if you are concerned about your child's appearance to make the iris look rounder.¹⁵

Orbital hypertelorism

Orbital hypertelorism is a congenital condition that can be defined as the presence of abnormal distance between the orbits (eye sockets), making the eyes look farther apart than usual.^{1 16} Orbital hypertelorism can be seen if you have Catel-Manzke syndrome.¹ Surgeries are available, bringing the orbits and eyes closer, but it's only for cosmetic purposes.¹⁷

Summary

Catel-Manzke syndrome is a rare disorder; only approximately 1,000 individuals have been reported in the medical literature with this disorder, and the incidence and prevalence are unknown ^{1 8} Catel-Manzke syndrome is associated with TGDS mutations, and it is a congenital recessive disorder, which means both parents are gene carriers.¹ 

This condition is characterised by distinctive symptoms such as abnormal fingers and facial features.^1,4 The most distinctive and one of the most common symptoms is the presence of Pierre-Robin sequence: micrognathia, glossoptosis, and airway blockage. Micrognathia is a condition in which the baby is born with a smaller jaw, which can lead to difficulty in breathing and feeding. Glossoptosis can be defined as the posterior (back side) positioning of the tongue and can restrict the flow of air and cause breathing difficulties. 

In severe cases, a breathing tube can be inserted through the neck to ease breathing, and a feeding tube can be inserted to improve the condition of the baby. Additionally, but less frequently, high arched eyebrows, prominent nasal bridge, low-set or abnormally shaped ears, and full cheeks can be observed as unusual facial features with this disorder. Eyes may be positioned farther apart than usual, and a gap in the iris, a condition called iris coloboma, may be present.¹ 

Knowing the features that may come with this disorder will allow you to understand what the possible challenges your child may face and give you the chance to educate yourself on how to support when needed to increase the comfort and life expectancy of your child. 

Symptomatic treatment and support may require coordination of different specialists.  Collaboration of paediatricians, geneticists, cardiologists, craniofacial surgeons, and other healthcare professionals is crucial to ensure the most effective treatment for your child.¹