Introduction

Hanhart syndrome is a rare congenital medical condition that belongs to the oromandibular-limb hypogenesis syndromes (OLHS) group. Conditions within the OLHS group are characterised by underdeveloped limbs, mouth, and jaw.¹ Hanhart syndrome was first diagnosed by Dr Hanhart in 1950 where three children had missing tongues and underdeveloped limbs.¹ 

What causes hanhart syndrome is not fully known and cases are believed to occur randomly with no real cause.¹ There has been no identification of the genes that are disease-causing.² However, some studies show that disease may be inherited as an autosomal recessive inheritance pattern.¹ Autosomal recessive inheritance patterns means that for a baby to have hanhart syndrome, they will need to inherit two copies of the mutated gene, one from each parent. Parents who are consanguineous (close relatives) have a higher chance of carrying the same mutated gene¹ and this will increase the chance of their children to inherit both of the affected gene, leading to hanhart syndrome. There is also the same risk of inheritance for both female and male babies. 

Some researchers believe that hanhart syndrome may occur due to a disruption in the blood supply to the limbs during embryonic development, leading them to become underdeveloped. This theory believes that a blood clot can form in the blood vessels, blocking, and disrupting the blood flow to the developing embryo and the blood clots could be due to certain medication taken by the mother.¹

Hanhart syndrome is a rare birth defect that affects less than 1 in 20,000 babies and only 30 cases of Hanhart syndrome have been discussed in literature from 1932 to 1991.¹ 

Hanhart syndrome is also known by other names:¹

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

It is important to diagnose Hanhart syndrome from other diseases to correctly manage the disease and prepare for any complications of the disorder. However, there are some challenges in diagnosing Hanhart syndrome. Hanhart syndrome is very rare, and this means that it is not familiar to clinicians and to health professionals, which means that the results may be misdiagnosed and an incorrect treatment used to treat the disease. With hanhart syndrome, the clinical features vary with patients and the variability will impede on diagnosis. Hanhart syndrome shares many symptoms that are present in congenital conditions such as limb malformation and craniofacial abnormalities, and this makes it different to differentiate hanhart syndrome from other syndromes.

Clinical Features of Hanhart Syndrome:

Hanhart syndrome clinical features include:²

• Underdeveloped tongue
• Small mouth with short or underdeveloped tongue
• Short or absent fingers and toes
• Jaw abnormalities like underdeveloped lower jaw (micrognathism), underdeveloped upper jaw (retrognathism)
• Underdeveloped or shorten arms and legs

Craniofacial abnormalities is a common clinical feature found in children with hanhart syndrome and these include as discussed above, small mouth with short, underdeveloped tongue, cleft palate, and cleft tongue, board nose and eyelid defects.¹ Children can also have fingers and toes that are missing or underdeveloped, alongside parts of the arms and legs being shortened too.¹ Limb abnormalities can vary from limb to limb in how severe they are and could affect one side more than another.

Motor functions are also affected in children, where nerves in the facial area could be affected leading to paralysis in certain facial areas.¹ This can worsen feeding problems, especially if there is already tongue, and jaw abnormalities.¹ In some patients, intellectual disabilities could be present too.¹ 

There is variety in the symptom and clinical features in hanhart syndrome patients and this can be due to specific gene mutations, but as the specific gene is not fully known, more research is needed to understand the genotype-phenotype correlations.

Conditions to consider in Differential Diagnosis:

Hanhart syndrome shares similar symptoms as the following conditions:

• Orofacial-digital syndrome
• Moebius Syndrome
• Poland Syndrome
• Acrofacial Dysostosis 
• Ankyloglossia superior Syndrome
• Charlie M syndrome

Orofacial-Digital syndrome: 

Orofacial-digital syndrome (ODS) is a group of conditions that affects development of the mouth, tongue, teeth and jaw, the face, and digits.³ Common features of ODS that are similar to hanhart syndrome include a cleft, missing teeths, shortened fingers and toes, and intellectual disability.

ODS differs from Hanhart syndrome as ODS is accompanied by CNS involvement like seizures, uncontrollable movements, and delayed speech.³ The genetic cause of most conditions of ODS is known alongside its inheritance pattern.³

Moebius Syndrome:

Moebius syndrome is another rare medical condition that occurs at birth and it affects muscles involved in the control of facial expression and the eye movement. Underdeveloped tongue, jaw, and limbs are also common features of Moebius syndrome that overlap with symptoms of hanhart syndrome.⁴ Moebius syndrome's main difference from hanhart syndrome lies in Moebius's lack of facial expression.

Poland Syndrome:

Poland syndrome is another rare congenital disease where the chest wall muscle on one side of the body is missing and the fingers are short and webbed on the same side.⁵ The cause for poland syndrome like hanhart syndrome is unknown and is thought to occur randomly.⁵ Poland syndrome differs from hanhart syndrome, as only one side of the body is affected whilst in hanhart syndrome it could be both sides, even if one side is more affected.

Nager acrofacial Dysostosis:

Nager syndrome is another rare genetic disease where one is born with underdeveloped bones in the face, arms and hands. Nager syndrome symptoms that are similar to hanhart syndrome include a cleft palate, small underdeveloped jaw, shortened arms and malformed fingers.⁶ The cause of Nager syndrome is also known and is caused by a mutation of the SF3B4 gene and it is inherited as an autosomal inheritance pattern.⁶

Ankyloglossia superior Syndrome:

Ankyloglossia superior syndrome (ASS) is a very rare disease that occurs when the fibrous connection that connects the tongue to the mouth is malformed leading to clinical observation similar to hanhart syndrome like a cleft palate, deformed limbs and underdeveloped tongue.

Charlie M syndrome:

Charlie M syndrome is a rare bone development that belongs to the same OLHS group as hanhart syndrome. Charlie M syndrome also has similar symptoms like a small mouth, cleft palate, underdeveloped mouth, facial paralysis, and shortened limbs.

Diagnostic Approach

As Hanhart syndrome shares many symptoms and clinical features as other medical conditions, diagnosis is therefore important to prevent misdiagnosis. Typically hanhart syndrome is diagnosed through clinical evaluation and physical testing.¹

Clinical evaluation depends on first taking a detailed patient history including family history. Even though the exact cause of hanhart syndrome is not fully known, it is inherited as an autosomal recessive pattern. Understanding if parents are carriers is important for family planning and to prevent future children having hanhart syndrome. Clinical evaluation also includes taking a physical examination of the limb malformation and the craniofacial abnormalities.  

Genetic testing would be important for confirming diagnosis but as the exact disease causing gene is unknown, genetic testing is not available for diagnosing hanhart syndrome. 

Imaging could also be used like MRI and X-rays to confirm skeletal abnormalities.

Management & Prognosis

It is important to diagnose hanhart syndrome early and get an accurate diagnosis as this will have an impact on the treatment planning and in genetic counselling. Treatment of hanhart syndrome is an interdisciplinary and multi-member effort where a team of specialists like paediatricians, orthopaedic surgeons, and speech and physical therapists have to work together to plan the treatment for hanhart syndrome.¹ 

Babies with hanhart syndrome can have feeding difficulties as their mouth, jaw, and tongue are underdeveloped and this can be treated surgically using artificial prosthetics alongside physical therapist.¹ Speech therapists are also involved in treating hanhart syndrome, especially if speech is impacted.¹

Limb abnormalities can affect motor skills and can impact children in their walking, running, and writing, and this can be addressed surgically once again using artificial prosthetics to replace missing limbs alongside physical therapy too. 

Hanhart syndrome will require long-term follow up and care consideration. Treatments can also be supportive, supporting the family. Treatment will also vary depending on the severity of hanhart syndrome. 

Conclusion

Hanhart syndrome is a rare congenital medical condition that is characterised by underdeveloped limbs, mouth, and jaw.¹ The cause of Hanhart syndrome is not known and the disease causing gene is not known either, but it is thought that hanhart syndrome is inherited as an autosomal recessive inheritance pattern. 

Symptoms of hanhart syndrome include:

• Underdeveloped tongue
• Small mouth with short or underdeveloped tongue
• Short or absent fingers and toes
• Jaw abnormalities like underdeveloped lower jaw (micrognathism), underdeveloped upper jaw (retrognathism)
• Underdeveloped or shorten arms and legs

There is variety in the symptom and clinical features in hanhart syndrome patients but the real reason behind this is also unknown. 

Hanhart syndrome shares many symptoms that are present in congenital conditions such as limb malformation and craniofacial abnormalities and this makes it different to differentiate hanhart syndrome from other syndrome.

Hanhart syndrome shares similar symptoms as the following conditions and could therefore be mistaken for:

• Orofacial-digital syndrome
• Moebius Syndrome
• Poland Syndrome
• Acrofacial Dysostosis 
• Ankyloglossia superior Syndrome
• Charlie M syndrome

As Hanhart syndrome shares many symptoms and clinical features as other medical conditions, diagnosis is therefore important to prevent misdiagnosis. Typically hanhart syndrome is diagnosed through clinical evaluation and physical testing.¹

It is important to diagnose hanhart syndrome early and get an accurate diagnosis as this will have an impact on the treatment planning and in genetic counselling. Hanhart syndrome will require long-term follow up and care consideration.