Hanhart syndrome (also known as Aglossia adactylia; Hypoglossia-hypodactylia syndrome; Peromelia with micrognathia; Jussieu syndrome) is a broadly classified medical condition consisting of congenital disorders that cause an undeveloped tongue and malformed extremities and fingers. There exist five types of Hanhart syndrome, with the severity and nature of the condition ranging widely on a case-by-case basis. Hanhart syndrome is classified as a rare disease, with only 30 known cases having been diagnosed between 1932 and 1991. Early hypotheses believed that the disease was caused by genetic conditions, with a more recent hypothesis demonstrating evidence that the disease may be caused by hemorrhagic lesions during prenatal development. The causal mechanism behind this vascular disruption is still unknown.

Discovery and etymology

Hanhart syndrome was first described in 1932 by Dr. Ernst Hanhart. The name 'Hanhart syndrome' was not used until 1950 when Dr. Hanhart described three patients who were born with limb defects and missing tongues. In 1971, the syndrome was more broadly classified as 'syndromes of oromandibular and limb hypogenesis', and comprised a range of disorders that all share hypoglossia. The name ''hypoglossia-hypodactylia syndrome' was proposed in 1971 as a more accurate name for the disorder, which is used synonymously. Due to the wide range of symptoms presented in Hanhart syndrome, the disorder has received many different names throughout its diagnostic history.

Pathophysiology

Hanhart syndrome is part of the larger ' oromandibular-limb hypogenesis syndrome (OLHS)' family of conditions, which are collectively characterized by the underdevelopment of the mouth, jaw, tongue, and extremities. Hanhart syndrome is characterized by an underdeveloped tongue ( hypoglossia), small mouth (

microstomia Microstomia is a small mouth (''micro-'' a combining form meaning small + ''-stomia'' a combining form meaning mouth = (abnormally) "small mouth" in Greek.) Congenital It is a feature of many craniofacial syndromes, including Freeman–Sheldon ...

), smaller than average jaw size ( micrognathia), clefting or abnormal attachment of the tongue, missing teeth (mandibular hypodontia), cleft palate,

cranial nerve palsies Cranial nerve disease is an impaired functioning of one of the twelve cranial nerves. Although it could theoretically be considered a mononeuropathy, it is not considered as such under MeSH. It is possible for a disorder of more than one crania ...

including Möbius syndrome, broad nose, increased distance between the eyes ( telecanthus), defects in the lower eyelids, and

facial asymmetry Facial symmetry is one specific measure of bodily symmetry. Along with traits such as averageness and youthfulness it influences judgments of aesthetic traits of physical attractiveness and beauty. For instance, in mate selection, people have be ...

Limbs generally present as underdeveloped (

hypoplasia Hypoplasia (from Ancient Greek ὑπo- ''hypo-'' 'under' + πλάσις ''plasis'' 'formation'; adjective form ''hypoplastic'') is underdevelopment or incomplete development of a tissue or organ.phalanx bones (

hypodactylia Oligodactyly (from Ancient Greek ''oligos'' 'few' and δάκτυλος ''daktylos'' 'finger') is the presence of fewer than five fingers or toes on a hand or foot.

) to incomplete adactyly to partial amputation or malformation of the limbs (peromelia). In cases where limb defects are involved, they generally involve all four extremities. Complete loss of the tongue ( aglossia) and fingers (adactylia) have not been reported. Less common symptoms include externally visible intestines ( gastroschisis) and abnormal fusion of the spleen and

gonad A gonad, sex gland, or reproductive gland is a mixed gland that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gonad, the testicle, produces sper ...

s ( splenogonadal fusion).

Supernumerary nipple A supernumerary nipple is an additional instance of nipple occurring in mammals, including humans. They are often mistaken for moles. Studies variously report the prevalence of supernumerary nipples as approximately 1 in 18 and 1 in 40. https:// ...

s, microcephaly, and micropenis have also been identified as possible symptoms. Ultrasound examination of the cranial and abdominal regions in patients has found that internal structures are unaffected by Hanhart syndrome. Mental disabilities are uncommon, but feeding and speech deficits have been reported in some cases. The severity of these disabilities can vary greatly from person to person, and patients with the disorder often present some, but not all, of the symptoms. Hanhart syndrome is classified by 5 types, denoting the symptoms and severity of the condition. Type I involves hypoglossia and partial aglossia without any other symptoms. Type II involves hypoglossia with hypomelia or hypodactylia. Type III includes hypoglossia with glossopalatine ankylosis and hypomelia or hypodactyly. Type IV involves fused inter-oral bands with hypoglossia or hypomelia/hypodactyly. Type V involves several co-morbid syndromes alongside Hanhart syndrome, including: Pierre Robin syndrome, Mobius syndrome, and amniotic band syndrome.

Causes and prevalence

The causes of Hanhart syndrome and other OLHS conditions is unknown, but both genetic and environment factors have been proposed. Hanhart syndrome follows an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

inheritance pattern, has a population prevalence of <1/1,000,000, and due to its rarity has been classified as a rare disease. Between 1932 and 1991, 30 case of Hanhart syndrome were diagnosed, and the survival rate for affected individuals is approximately 30%. The prevalence of Hanhart syndrome within consanguineous patients lead to an early hypothesis that a mutation in an autosomal recessive gene led to the condition. To date, no specific genes have been identified. In 1973, a hypothesis that hemorrhagic lesions during prenatal development were the cause of Hanhart Syndrome was proposed. This hypothesis asserts that vascular lesions result in decreased blood flow to the limbs, tongue, and rarely parts of the brain, causing developmental malformation in the affected parts of the body.

Chorionic villous sampling Chorionic villus sampling (CVS), sometimes called "chorionic ''villous'' sampling" (as "villous" is the adjectival form of the word "villus"), is a form of prenatal diagnosis done to determine chromosomal abnormalities, chromosomal or genetic dis ...

(CVS) has shown a correlation between vascular disruption and later diagnosis of Hanhart Syndrome in developing embryos. Animal studies have shown that vascular disruptions in the fourth embryonic week can result in Hanhart syndrome, but the mechanism of this disruption is still unknown. Interactions between the

ectoderm The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm (the middle layer) and endoderm (the innermost layer). It emerges and originates from t ...

al and

mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical E ...

al germ layers, and the use of meclizine hydrochloride during pregnancy have been proposed as a potential causes. It has also been proposed that Poland syndrome and Hanhart syndrome may have similar causes and represent the spectrum of a larger disease.

Diagnosis and treatments

Diagnosis of Hanhart syndrome previously used CVS during the early stages of pregnancy, first 10 weeks of amenorrhoea. This would be able to test for vascular disruption during fetal development. This testing method has since been abandoned due a correlation between CVS early in a pregnancy and oromandibular limb dysgenesis, leading to a decrease in prenatal diagnoses.

Differential diagnosis In healthcare, a differential diagnosis (abbreviated DDx) is a method of analysis of a patient's history and physical examination to arrive at the correct diagnosis. It involves distinguishing a particular disease or condition from others that p ...

of Hanhart syndrome must rule out Nager syndrome and acro-facial dysostosis, Johnson Hall Krous Syndrome, and Goldenhar Syndrome. These syndromes are differentiated by the type and severity of facial and limb deformities. Treatments for Hanhart syndrome vary depending on the specific symptoms per patient. Treatments may include orthopedic and/or plastic surgery to treat for limb deformities. Special consideration of the airway must be taken during operations under

anesthesia Anesthesia is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia (relief from or prevention of pain), paralysis (muscle relaxation), ...

due to craniofacial deformities.

Notable cases

* Nick Santonastasso, motivational speaker, who has no legs and only one arm.

References

External links

* Omimbr>database of known cases (1950-2010)
{{Medical resources , ICD10 = Q87.2 , ICD9 = , ICDO = , OMIM = 103300 , DiseasesDB = , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeSH = , GeneReviewsNBK = , GeneReviewsName = , Orphanet = 989 Musculoskeletal disorders Congenital disorders of musculoskeletal system Rare syndromes Syndromes affecting the tongue Syndromes with dysmelia