Hanhart syndrome

Last updated

Hanhart syndrome
Infant with Mobius syndrome.jpg
An infant with Möbius syndrome and Oromandibular-limb hypogenesis syndrome, exhibiting similar symptoms to Hanhart syndrome
Symptoms Underdevelopment of the mouth, jaw, tongue, and extremities
Usual onset Neonatal, antenatal
DurationLifelong
CausesVascular disruption during fetal development
Differential diagnosis Nager acrofacial dysostosis

Johnson Hall Krous syndrome

Goldenhar syndrome
Frequency<1/1,000,000, 30 known cases

Hanhart syndrome [lower-alpha 1] 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 approximately 30 known cases having been reported between 1932 and 1991. Early hypotheses believed that the disorder was caused by genetic conditions, with a more recent hypothesis demonstrating that the disorder may be caused by hemorrhagic lesions during prenatal development. The causal mechanism behind this vascular disruption is still unknown.

Contents

Discovery and etymology

Hanhart syndrome was first described in 1932 by Ernst Hanhart. The name "Hanhart syndrome" was not used until 1950 when Hanhart described three patients who were born with limb defects and missing tongues. [1] 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. [2] [3] Due to the wide range of symptoms presented in Hanhart syndrome, the disorder has received many different names throughout its diagnostic history. [4]

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. [2] [1] Hanhart syndrome is characterized by an underdeveloped tongue (hypoglossia), small mouth (microstomia), smaller than average jaw size (micrognathia), clefting or abnormal attachment of the tongue, missing teeth (mandibular hypodontia), cleft palate, cranial nerve palsies including Möbius syndrome, broad nose, increased distance between the eyes (telecanthus), defects in the lower eyelids, and facial asymmetry. [2] [1] [5]

A 1 year old with oligodactyly, a symptom of Hanhart syndrome Deux pieds 1 an.jpg
A 1 year old with oligodactyly, a symptom of Hanhart syndrome

Limbs generally present as underdeveloped (hypoplasia), which can vary from missing phalanx bones (hypodactylia) 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. [5] Complete loss of the tongue (aglossia) and fingers (adactylia) have not been reported. [3] Less common symptoms include externally visible intestines (gastroschisis) and abnormal fusion of the spleen and gonads (splenogonadal fusion). [5] Supernumerary nipples, microcephaly, and micropenis have also been identified as possible symptoms. [6] Ultrasound examination of the cranial and abdominal regions in patients has found that internal structures are unaffected by Hanhart syndrome. [7] Mental disabilities are uncommon, but feeding and speech deficits have been reported in some cases. [5] 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. [2] [1]

Hanhart syndrome is classified by five 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. [3] [8]

Causes and prevalence

The causes of Hanhart syndrome and other OLHS conditions is unknown, but both genetic and environment factors have been proposed. [9] Hanhart syndrome follows an autosomal dominant inheritance pattern, has a population prevalence of <1/1,000,000, and due to its rarity has been classified as a rare disease. [5] [10] Between 1932 and 1991, about 30 case of Hanhart syndrome were reported in the literature. [5]

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. [5] To date, no specific genes have been identified. [7] In 1973, a hypothesis that hemorrhagic lesions or blood clots 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. [1] [5] 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. [11] Interactions between the ectodermal and mesodermal germ layers, [4] and the use of meclizine hydrochloride during pregnancy have been proposed as a potential causes. [12] It has also been proposed that Poland syndrome and Hanhart syndrome may have similar causes and represent the spectrum of a larger disorder. [4]

The use of chorionic villous sampling (CVS) has also been identified as a contributing factor to pathogensis. When CVS is used during the early stages of pregnancy, specifically during the first 10 weeks of amenorrhoea, there is an increased correlation with risk of the fetus developing Hanhart syndrome. Furthermore, the use of CVS is known to introduce vascular damages to the fetus, causing oromandibular limb dysgenesis and other prenatal disorders, giving credence to the vascular disruption hypothesis. [13] [5] [1]

Diagnosis and treatments

Diagnosis of Hanhart syndrome relies on clinical presentation. [11] Differential diagnosis of Hanhart syndrome must rule out Nager syndrome and acro-facial dysostosis, Johnson Hall Krous syndrome, and Goldenhar syndrome. [11] [5] These syndromes are differentiated by the type and severity of facial and limb deformities. [5]

Treatments for Hanhart syndrome vary depending on the specific symptoms per patient. [2] Treatments may include orthopedic or plastic surgery to treat for limb deformities. [5] These can include surgical correction of the tongue, mouth, and jaw regions, as well as the use of prostheses and physical therapy. Speech therapy is another common treatment for facial deformities. [1] Special consideration of the airway is often taken during operations under anesthesia due to craniofacial deformities. [11]

Notable cases

Related Research Articles

<span class="mw-page-title-main">Ehlers–Danlos syndrome</span> Group of genetic connective tissues disorders

Ehlers–Danlos syndromes (EDS) are a group of 13 genetic connective-tissue disorders. Symptoms often include loose joints, joint pain, stretchy velvety skin, and abnormal scar formation. These may be noticed at birth or in early childhood. Complications may include aortic dissection, joint dislocations, scoliosis, chronic pain, or early osteoarthritis. The current classification was last updated in 2017, when a number of rarer forms of EDS were added.

<span class="mw-page-title-main">Moebius syndrome</span> Facial muscle paralysis from birth

Möbius syndrome or Moebius syndrome is a rare congenital neurological disorder which is characterized by facial paralysis and the inability to move the eyes from side to side. Most people with Möbius syndrome are born with complete facial paralysis and cannot close their eyes or form facial expressions. Limb and chest wall abnormalities sometimes occur with the syndrome. People with Möbius syndrome have normal intelligence, although their lack of facial expression is sometimes incorrectly taken to be due to dullness or unfriendliness. It is named for Paul Julius Möbius, a German neurologist who first described the syndrome in 1888. In 1994, the "Moebius Syndrome Foundation" was founded, and later that year the first "Moebius Syndrome Foundation Conference" was held in Los Angeles.

Timothy syndrome is a rare autosomal-dominant disorder characterized by physical malformations, as well as neurological and developmental defects, including heart QT-prolongation, heart arrhythmias, structural heart defects, syndactyly, and autism spectrum disorders. Timothy syndrome represents one clinical manifestation of a range of disorders associated with mutations in CACNA1C, the gene encoding the calcium channel Cav1.2 α subunit.

<span class="mw-page-title-main">Primrose syndrome</span> Medical condition

Primrose syndrome is a rare, slowly progressive genetic disorder that can vary symptomatically between individual cases, but is generally characterised by ossification of the external ears, learning difficulties, and facial abnormalities. It was first described in 1982 in Scotland's Royal National Larbert Institution by Dr D.A.A. Primrose.

<span class="mw-page-title-main">Apert syndrome</span> Congenital disorder of the skull and digits

Apert syndrome is a form of acrocephalosyndactyly, a congenital disorder characterized by malformations of the skull, face, hands and feet. It is classified as a branchial arch syndrome, affecting the first branchial arch, the precursor of the maxilla and mandible. Disturbances in the development of the branchial arches in fetal development create lasting and widespread effects.

<span class="mw-page-title-main">Macroglossia</span> Enlargement of the tongue

Macroglossia is the medical term for an unusually large tongue. Severe enlargement of the tongue can cause cosmetic and functional difficulties in speaking, eating, swallowing and sleeping. Macroglossia is uncommon, and usually occurs in children. There are many causes. Treatment depends upon the exact cause.

<span class="mw-page-title-main">Hemifacial microsomia</span> Birth defect which affects the lower half of the face

Hemifacial microsomia (HFM) is a congenital disorder that affects the development of the lower half of the face, most commonly the ears, the mouth and the mandible. It usually occurs on one side of the face, but both sides are sometimes affected. If severe, it may result in difficulties in breathing due to obstruction of the trachea—sometimes even requiring a tracheotomy. With an incidence in the range of 1:3500 to 1:4500, it is the second most common birth defect of the face, after cleft lip and cleft palate. HFM shares many similarities with Treacher Collins syndrome.

Monosomy 9p is a rare chromosomal disorder in which some DNA is missing or has been deleted on the short arm region, "p", of one copy of chromosome 9 (9p22.2-p23). This deletion either happens de novo or as a result of a parent having the chromosome abnormality. This rare chromosomal abnormality is often diagnosed after birth when developmental delay, irregular facial features, structural irregularities within the heart, and genital defects are observed. Treatments for this syndrome usually focus on fixing the malformations that are commonly associated with it. The cause of the syndrome was first discovered in 1973, when an analysis of the chromosomes of three infants with similar clinical abnormalities revealed that they all had a partial deletion of the short arm of Chromosome 9. Symptoms include micro genitalia, intellectual disability with microcephaly and dysmorphic features.

Hypoglossia is a short, incompletely developed tongue. It can occur either as an isolated malformation or in association with other deformities, particularly limb defects in a syndrome known as oromandibular limb hypogenesis syndrome.

<span class="mw-page-title-main">3C syndrome</span> Medical condition

3C syndrome is a rare condition whose symptoms include heart defects, cerebellar hypoplasia, and cranial dysmorphism. It was first described in the medical literature in 1987 by Ritscher and Schinzel, for whom the disorder is sometimes named.

<span class="mw-page-title-main">Antley–Bixler syndrome</span> Congenital disorder

Antley–Bixler syndrome is a rare, severe autosomal recessive congenital disorder characterized by malformations and deformities affecting the majority of the skeleton and other areas of the body.

<span class="mw-page-title-main">Frontonasal dysplasia</span> Medical condition

Frontonasal dysplasia (FND) is a congenital malformation of the midface. For the diagnosis of FND, a patient should present at least two of the following characteristics: hypertelorism, a wide nasal root, vertical midline cleft of the nose and/or upper lip, cleft of the wings of the nose, malformed nasal tip, encephalocele or V-shaped hair pattern on the forehead. The cause of FND remains unknown. FND seems to be sporadic (random) and multiple environmental factors are suggested as possible causes for the syndrome. However, in some families multiple cases of FND were reported, which suggests a genetic cause of FND.

<span class="mw-page-title-main">Orofaciodigital syndrome 1</span> Medical condition

Orofaciodigital syndrome 1 (OFD1), also called Papillon-Léage and Psaume syndrome, is an X-linked congenital disorder characterized by malformations of the face, oral cavity, and digits with polycystic kidney disease and variable involvement of the central nervous system.

<span class="mw-page-title-main">Klippel–Trénaunay syndrome</span> Medical condition

Klippel–Trénaunay syndrome, formerly Klippel–Trénaunay–Weber syndrome and sometimes angioosteohypertrophy syndrome and hemangiectatic hypertrophy, is a rare congenital medical condition in which blood vessels and/or lymph vessels fail to form properly. The three main features are nevus flammeus, venous and lymphatic malformations, and soft-tissue hypertrophy of the affected limb. It is similar to, though distinct from, the less common Parkes Weber syndrome.

<span class="mw-page-title-main">Bonnet–Dechaume–Blanc syndrome</span> Medical condition

Bonnet–Dechaume–Blanc syndrome, also known as Wyburn-Mason syndrome, is a rare congenital disorder characterized by arteriovenous malformations of the brain, retina or facial nevi. The syndrome has a number of possible symptoms and can, more rarely, affect the skin, bones, kidneys, muscles, and gastrointestinal tract. When the syndrome affects the brain, people can experience severe headaches, seizures, acute stroke, meningism, and progressive neurological deficits due to acute or chronic ischaemia caused by arteriovenous shunting.

<span class="mw-page-title-main">Parkes Weber syndrome</span> Medical condition

Parkes Weber syndrome (PWS) is a congenital disorder of the vascular system. It is an extremely rare condition, and its exact prevalence is unknown. It is named after British dermatologist Frederick Parkes Weber, who first described the syndrome in 1907.

<span class="mw-page-title-main">Constriction ring syndrome</span> Medical condition

Constriction ring syndrome (CRS) is a congenital disorder with unknown cause. Because of the unknown cause there are many different, and sometimes incorrect names. It is a malformation due to intrauterine bands or rings that give deep grooves in, most commonly, distal extremities like fingers and toes. In rare cases the constriction ring can form around other parts of the fetus and cause amputation or even intrauterine death. The anatomy proximal to the site of constriction is developmentally normal. CRS can be associated with other malformations with club foot being most common. The precise configuration of the bands, lymphedema, and character of the amputations are not predictable and vary with each individual patient. Also, more than one extremity is usually affected, and it is rare for only one ring to present as an isolated malformation with no other manifestation of this syndrome.

<span class="mw-page-title-main">Young–Madders syndrome</span> Genetic disorder

Young–Madders syndrome, alternatively known as Pseudotrisomy 13 syndrome or holoprosencephaly–polydactyly syndrome, is a genetic disorder resulting from defective and duplicated chromosomes which result in holoprosencephaly, polydactyly, facial malformations and intellectual disability, with a significant variance in the severity of symptoms being seen across known cases. Many cases often suffer with several other genetic disorders, and some have presented with hypoplasia, cleft lip, cardiac lesions and other heart defects. In one case in 1991 and another in 2000 the condition was found in siblings who were the product of incest. Many cases are diagnosed prenatally and often in siblings. Cases are almost fatal in the prenatal stage with babies being stillborn.

Aglossia is a congenital defect resulting in a partial development or complete absence of a tongue.

<span class="mw-page-title-main">Van De Berghe Dequeker syndrome</span> Medical condition

Van Den Berghe Dequeker syndrome, also known as ulnar hypoplasia-split foot syndrome is a very rare congenital limb malformation syndrome which is characterized by severe ulnar hypoplasia, absence of the index to pinky finger in both hands, and split-foot.

References

  1. 1 2 3 4 5 6 7 "Hanhart Syndrome - National Organization for Rare Disorders". rarediseases.org. Archived from the original on 2021-09-30. Retrieved 2023-02-25.
  2. 1 2 3 4 5 "Hanhart syndrome - National Organization for Rare Disorders". rarediseases.org. 2022-06-16. Archived from the original on 2023-02-25. Retrieved 2023-02-25.
  3. 1 2 3 McKusick VA, Kniffin CL (August 8, 2016). "Hypoglossia-Hypodactylia". omim.org. Archived from the original on 2022-06-17. Retrieved 2023-02-25.
  4. 1 2 3 Herrmann J, Pallister PD, Gilbert EF, Vieseskul C, Bersu E, Pettersen JC, Opitz JM (April 1976). "Studies of malformation syndromes of man XXXXI B: nosologic studies in the Hanhart and the Möbius syndrome". European Journal of Pediatrics. 122 (1): 19–55. doi: 10.1007/BF00445030 . PMID   1261566. S2CID   23498856.
  5. 1 2 3 4 5 6 7 8 9 10 11 12 "Orphanet: Hypoglossia hypodactyly syndrome". www.orpha.net. Archived from the original on 2023-02-25. Retrieved 2023-02-25.
  6. ↑ Gathwala G, Singh J, Dalal P, Garg A (March 2011). "Hypoglossia-hypodactyly syndrome in a newborn". Journal of Cranio-Maxillo-Facial Surgery. 39 (2): 99–101. doi:10.1016/j.jcms.2010.06.007. PMID   20673638.
  7. 1 2 Varal IG, Dogan P (2019-04-29). "Hanhart syndrome: hypoglossia-hypodactylia syndrome". Pan African Medical Journal. 32 (1): 213. ISSN   1937-8688. PMC   6620079 . PMID   31312325. Archived from the original on 2023-02-26. Retrieved 2023-03-10.
  8. ↑ Goyal M, Singh A, Singh P, Kapoor S (April 2014). "Hypoglossia-hypodactyly syndrome with short stature - a case report". Journal of Clinical and Diagnostic Research. 8 (4): SD01–SD02. doi:10.7860/JCDR/2014/7809.4281 (inactive 2024-09-13). PMC   4064859 . PMID   24959494.{{cite journal}}: CS1 maint: DOI inactive as of September 2024 (link)
  9. ↑ Bersu ET, Pettersen JC, Charboneau WJ, Opitz JM (April 1976). "Studies of malformation syndromes of man XXXXIA: anatomical studies in the Hanhart syndrome--a pathogenetic hypothesis". European Journal of Pediatrics. 122 (1): 1–17. doi:10.1007/BF00445029. PMID   1261565. S2CID   10440385.
  10. ↑ "Hanhart syndrome - About the Disease - Genetic and Rare Diseases Information Center". rarediseases.info.nih.gov. Archived from the original on 2023-01-05. Retrieved 2023-02-25.
  11. 1 2 3 4 Bissonnette, Bruno; Luginbuehl, Igor; Engelhardt, Thomas (2019), "Hypoglossia-Hypodactylia Syndrome", Syndromes: Rapid Recognition and Perioperative Implications (2 ed.), New York, NY: McGraw-Hill Education, archived from the original on 2023-03-10, retrieved 2023-02-27
  12. ↑ Bökesoy I, Aksüyek C, Deniz E (July 1983). "Oromandibular limb hypogenesis/Hanhart's syndrome: possible drug influence on the malformation". Clinical Genetics. 24 (1): 47–49. doi:10.1111/j.1399-0004.1983.tb00068.x. PMID   6616945. S2CID   43535751.
  13. ↑ Chen, C. P.; Liu, F. F.; Jan, S. W.; Lin, S. P.; Lan, C. C. (1996-06-14). "CVS-exposed limb deficiency defects with or without other birth defects: presentation of six cases born during a period of nine years". American Journal of Medical Genetics. 63 (3): 447–453. doi:10.1002/(SICI)1096-8628(19960614)63:3<447::AID-AJMG6>3.0.CO;2-O. ISSN   0148-7299. PMID   8737650.
  14. ↑ Petter O (20 July 2017). "Bodybuilder with one arm and no legs becomes internet sensation". The Independent . Archived from the original on 19 April 2018. Retrieved 19 April 2018.
  15. ↑ Stump S (October 2016). "'Dead' man living: Disabled teen-turned-Internet star 'lives by inspiring others'". Today. Archived from the original on 2018-04-19. Retrieved 2018-04-19.

Notes

  1. ↑ Also known as Aglossia adactylia; Hypoglossia-hypodactylia syndrome; Peromelia with micrognathia; and Jussieu syndrome
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.