Overview of Hanhart Syndrome

Hanhart Syndrome is an incredibly rare congenital disorder affecting only a handful of children. Only 30 cases of Hanhart syndrome were reported between 1932 and 1991 in the medical literature.¹ There is no significant disparity between the number of boys and the number of girls affected by the syndrome. 

Although the syndrome was first described in 1932, it was not referred to as Hanhart syndrome until 1950 when Dr Hanhart described three cases of babies born without a tongue and associated limb defects.¹ In 1971, Dr Hall coined the term ‘syndromes of oromandibular and limb hypogenesis’ which encompasses a range of disorders (including Hanhart syndrome).² 

Nowadays, several terms are used synonymously:

• Aglossia-Adactylia
• Hypoglossia-hypodactylia syndrome
• Peromelia with micrognathia 

The severity of the physical abnormalities observed in Hanhart syndrome varies between individuals, with some patients displaying more abnormalities than others. Due to the variation in severity, Hanhart Syndrome has been classified into 5 types:²

• Type I relates to hypoglossia and aglossia alone 
• Type II includes hypoglossia in combination with hypodactylia or hypomelia (shortened limbs) 
• Type III is characterised by glossopalatine ankylosis with hypoglossia and hypodactylia or hypomelia. 
• Type IV is hypoglossia and hypomelia/hypodactylia or intraoral bands fusion with hypoglossia 
• Type V is the presence of several congenital syndromes, such as Pierre Robin syndrome, alongside Hanhart syndrome  

Clinical Manifestations of Hanhart Syndrome

Although the clinical manifestations vary between cases, there are some common signs and symptoms that can be attributed to Hanhart syndrome. Craniofacial anomalies commonly seen include:¹

• Microstomia: A small mouth. This can cause difficulty eating, speaking and maintaining good oral health
• Micrognathia: The lower jaw is smaller than normal. This can result in feeding and breathing difficulties in babies
• Hypoglossia or aglossia: A short incompletely developed tongue or complete absence of the tongue. Problems with speech and feeding are inevitable
• Cleft palate or abnormal attachment of the tongue
• Telecanthus: Increased distance between the eyes

Absence or underdevelopment of fingers and toes (hypodactylia/adactylia) is also seen in patients affected by Hanhart syndrome.¹ Furthermore, limb abnormalities occur frequently. Portions of the arms and legs can be underdeveloped, malformed or missing completely (melia). 

Impairment in one or more of the 12 pairs of cranial nerves can lead to problems with motor function in the facial region (cranial nerve palsy).¹ Consequently, language and feeding problems can be exacerbated due to cranial nerve palsy in combination with the craniofacial anomalies stated above. 

It is possible to find no common anomaly upon ultrasonic examination.³ Mental disabilities are uncommon, but not unheard of in individuals diagnosed with the syndrome.¹ 

Less common physical anomalies may occur in conjunction with Hanhart syndrome, these can include: 

• Gastroschisis: Externally visible intestines
• Splenogonadal fusion: Fusion between the spleen and gonads (ovaries or testis) 
• Chryptochidism: Undescended testicles in men
• More than two nipples 
• An absent kidney
• Epicanthal folds of the eye
• Imperforate anus: Abnormally positioned or absent anus
• Club foot   

Causes and Diagnosis of Hanhart Syndrome

The precise cause of Hanhart syndrome remains a mystery and cases appear to occur sporadically. Several hypotheses have been proposed. Some researchers have reported an autosomal dominant inheritance.⁴ 

On the other hand, researchers hypothesise an autosomal recessive pattern of inheritance due to the higher prevalence of the syndrome in children of consanguineous parents.¹ Parents who are closely related are more likely to both carry the faulty gene and increase the risk of having a child with an autosomal recessive genetic disorder. 

Another hypothesis is that vascular disruptions during embryonic development are the cause of Hanhart syndrome.¹ Haemorrhage or occlusion decreases the blood supply to the developing limbs, tongue and facial area. The decreased perfusion may be a result of drug exposure. A group of clinicians reported that prenatal exposure to meclizine hydrochloride can affect embryonic blood supply and lead to Hanhart syndrome.⁵  

Diagnosing Hanhart syndrome relies wholly on clinical presentation. Other syndromes are differentiated from Hanhart by comparing the severity and type of physical abnormalities presented. 

Differential Diagnoses for Hanhart Syndrome 

There are several other syndromes with similar and overlapping symptoms to those of Hanhart syndrome. Comparing symptoms may be helpful for clinicians to differentiate between diagnoses. 

• Nager Syndrome: A genetic condition that mainly affects the bone and tissue development in the face but can also impact limbs
• Goldenhar syndrome: A congenital condition caused by vascular obstruction during embryonic development. It primarily affects the development of the eyes, ears and spine
• Charlie M Syndrome: This falls under the group of conditions labelled oromandibular and limb hypogenesis. It is rare and caused by a DNA mutation
• Moebius Syndrome: As a result of improper development of the cranial nerves. This impacts the movement of the eyes, mouth and tongue
• Poland’s Syndrome: A birth defect usually resulting in the absence of chest wall muscles on one side of the body and webbed fingers

Therapies to Manage Hanhart Syndrome

A multidisciplinary team is required to formulate a management plan for a child with Hanhart syndrome. Orthopaedic and plastic surgeons can help manage limb and facial deformities. Physical therapists can help overcome movement difficulties and fine-tune motor skills. Speech therapists are useful tools for aiding speech development in individuals with tongue and facial abnormalities. The use of prosthetics may also be very beneficial for individuals with missing limbs or extremities. 

Ensuring your home has a safe and supportive environment based on your child’s individual needs is essential. An occupational therapist and social services may have the resources and knowledge to help. 

Summary

In summary, Hanhart syndrome is a rare congenital disorder that primarily causes facial and limb abnormalities. The main clinical manifestations of Hanhart Syndrome are: A small mouth, absence of the tongue, receding jawline, missing fingers and toes and underdeveloped limbs. The exact cause remains uncertain with some clinicians suggesting a genetic basis whilst others indicate a vascular disruption during embryonic development to be the cause of Hanhart syndrome. Diagnosing Hanhart syndrome may prove to be a challenge due to a long list of differential diagnoses that needs to be ruled out before confirming the diagnosis. 

FAQs

How likely is it that my child is born with Hanhart Syndrome?

Hanhart syndrome is very rare. Between 1931 and 1992 only 30 cases were reported.  

How is Hanhart Syndrome diagnosed?

A clinician will assess the patient's signs and symptoms. Other differential diagnoses will be ruled out. 

What causes Hanhart Syndrome?

There are several hypotheses, including: 

• Autosomal dominant inheritance pattern
• Autosomal recessive inheritance pattern: Due to a high prevalence of the syndrome consanguineous parents
• Vascular disruption during embryonic development