|Year : 2015 | Volume
| Issue : 2 | Page : 271-273
Sudhir Malwade, Mohit Gupta, Sharad R Agarkhedkar
Department of Paediatrics, D. Y. Patil Medical College, Pimpri, Pune, Maharashtra, India
|Date of Web Publication||13-Mar-2015|
Department of Paediatrics, D. Y. Patil Medical College, Pimpri, Pune, Maharashtra
Source of Support: None, Conflict of Interest: None
Ambras syndrome, a form of congenital hypertrichosis lanuginosa, is extremely rare in neonates. It is characterized by typical pattern of hair distribution, dysmorphic facial features and a familial pattern of inheritance. We report a case of Ambras syndrome in a preterm neonate with history of consanguinity and positive family history.
Keywords: Ambras syndrome, congenital hypertrichosis lanuginosa, dysmorphic facial features
|How to cite this article:|
Malwade S, Gupta M, Agarkhedkar SR. Ambras syndrome. Med J DY Patil Univ 2015;8:271-3
| Introduction|| |
Ambras syndrome is a special form of congenital hypertrichosis (excessive hair growth at birth). It differs from other forms of generalized hypertrichosis in the pattern of hair distribution, associated dysmorphic facial features and possible dental abnormalities and a familial pattern of inheritance. 1993, Baumeister et al. first described the case of Ambras syndrome.  Until date, only 10 cases of Ambras syndrome has been documented in the literature. ,,, Two of these 10 cases have been associated with structural rearrangements of chromosome 8, involving the region 8q22-24. ,, We are reporting this rare syndrome in a preterm neonate born out of a consanguineous marriage in phenotypically normal parents with a positive family history supporting a familial pattern of genetic inheritance.
| Case Report|| |
A male preterm neonate weighing 1.1 kg, born to a 25 years old P3 L3 via normal vaginal delivery was admitted to NICU in view of mild HMD, preterm complications and low-birth weight. The neonate was noted to have excessive hair growth. His entire body including the face, back and external ear was covered with fine, light colored vellus hair sparing the palms, soles, and mucosa. He also had dysmorphic facial features like triangular facies and coarse features, hypertelorism, a wide and prominent nasal root, a large interalar distance, round nasal tip and anteverted nostrils. [Figure 1] and [Figure 2] depict these features. Histopathology confirmed the nature of hair to be vellus. There was no other congenital abnormality detected. Parents had second degree consanguinity. There was no significant maternal illness. Antenatal period was uneventful. There was no history of drug intake by the mother or radiation exposure. There was a positive family history in his elder male sibling and maternal grandfather.
|Figure 1: Depicts the dysmorphic facial features like triangular facies and coarse features, hypertelorism, a wide and prominent nasal root, a large interalar distance, round nasal tip and anteverted nostrils|
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|Figure 2: Depicts the body covered with fine vellus long hair, characteristically involves the shoulders, face, nose, and ears. A characteristic shawl distribution on their back. The hair of the external auditory canal is typically long and thick, hindering inspection of the auditory meatus|
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| Discussion|| |
Ambras syndrome is a special form of congenital hypertrichosis that differs from other types of generalized hypertrichosis in that it has a distinctive pattern of the hair distribution, facial dysmorphism and familial pattern of inheritance. Baumeister et al. first described this syndrome in 1993.  It is believed to be that of Petrus Gonzales. The Ambras name was given as his family portraits were discovered in Ambras castle amongst an art collection started by the Archduke Ferdinand II (1529-1595). The second case was reported by Bladucci et al. 
This condition has no specific racial, sex, and geographical distribution. There are no long-term medical or physical morbidities and mortalities. However, psychological sequelae may occur due to the need for the removal of excessive unwanted hair. Although it presents at birth, the quantity of the excessive hair may be limited at that time. Unlike congenital hypertrichosis lanuginosa, Ambras syndrome may show increased hair growth both in distribution and density as the patient ages, and the hair does not spontaneously involute. The entire body is covered with fine vellus long hair, sparing only the regions where normally hair does not grow such as the palms, soles, mucosa, dorsal terminal phalanges, labia minora, prepuce, and glans penis. The hypertrichosis characteristically involves the shoulders, face, nose, and ears. In some areas, the hair may be noted as long as several centimeters. The hair is longest over the spine. Most patients have hair in a characteristic shawl distribution on their back. The hair of the external auditory canal is typically long and thick, and it may hinder inspection of the auditory meatus. The dysmorphic facial features include the following: Triangular, coarse face, large intercanthal distance, broad palpebral fissures, long prominent back of the nose, round nasal tip, large interalar distance, anteverted nares, and flat sulcus mentolabialis. Dental abnormalities like anodontia, delayed primary, and secondary dentition may occur.  Other findings noted in solitary case reports include bushy eyebrows, accessory nipples. A family history of excessive body hair may exist.
Possible cause of hypertrichosis is increase in the number of hairs in anagen or from an increased number of follicular units.
A genetic etiology is proposed for Ambras syndrome. It is associated with alterations in chromosome 8 as analyzed in 2 out of 10 cases so far. These include pericentric inversion of chromosome 8, inv(8)(p11.2q22),  paracentric inversion inv(8)(q12q22),  or more complex insertion of the q23-24 region into a more proximal region of the long arm of chromosome 8, most likely at the q13 band, as well as a complex deletion in 8q23 encompassing four separate chromosomal breakpoints.  Although the relationship of these genetic observations to the pathogenesis of hypertrichosis remains uncertain, it has been postulated that the common breakpoint in both patients with Ambras syndrome at 8q22 suggests that this region of chromosome 8 contains a gene involved in the regulation of hair growth. Down regulation of TRPS1 expression is the probable cause of hypertrichosis in Ambras syndrome. 
The diagnosis is based on clinical and histologic findings, and no laboratory workup or imaging studies is necessary, except to exclude other causes of hypertrichosis. Diagnosis may be supported by inversions involving breakpoints in the region of band 8q22.
Hair biopsy findings may be diagnostic because the type of hair and position of the follicle found on histopathologic analysis can be helpful in excluding alternative diagnoses.
| Management|| |
To improve the appearance (goal of therapy): Use of eflornithine cream or hair removal by means of repeated shaving, depilatory methods (e.g., chemical, electric methods), bleaching or Laser. Antidepressant medications in patients with psychological sequelae, including depression. Genetic consultation - As it is considered to have autosomal dominant pattern of inheritance; however, an association with a genetic defect has not been demonstrated in all patients. Belengeanu et al.  described two siblings with reported Ambras syndrome born to normal parents and propose that these patients might represent either an autosomal recessive pattern or germline mosaicism.
In this case reported, the neonate has all the clinical features diagnostic of Ambras syndrome of Baumeister type, with positive family history. Although genetic analysis would have supported the diagnosis.
| Conclusion|| |
The diagnosis of Ambras Syndrome is mainly clinical; Characterized by a distinctive type of hypertrichosis at birth as described above, facial dysmorphism and familial pattern of inheritance. Genetic analysis may reveal chromosomal abnormality involving 8q22-24. However, identical mutations may cause phonotypical heterogenecity. Goal of therapy is mainly to improve physical appearance.
| References|| |
Baumeister FA, Egger J, Schildhauer MT, Stengel-Rutkowski S. Ambras syndrome: Delineation of a unique hypertrichosis universalis congenita and association with a balanced pericentric inversion (8) (p11.2; q22). Clin Genet 1993;44:121-8.
Balducci R, Toscano V, Tedeschi B, Mangiantini A, Toscano R, Galasso C, et al.
A new case of Ambras syndrome associated with a paracentric inversion (8) (q12; q22). Clin Genet 1998;53:466-8.
Tadin M, Braverman E, Cianfarani S, Sobrino AJ, Levy B, Christiano AM, et al.
Complex cytogenetic rearrangement of chromosome 8q in a case of Ambras syndrome. Am J Med Genet 2001;102:100-4.
Belengeanu V, Rozsnyai K, Gug C, Banateanu M, Farcas S, Belengeanu A. Ambras syndrome: Report on two affected siblings with no prior family history. Clin Dysmorphol 2004;13:265-7.
Rashid RM, White LE. A hairy development in hypertrichosis: A brief review of Ambras syndrome. Dermatol Online J 2007;13:8.
Fantauzzo KA, Tadin-Strapps M, You Y, Mentzer SE, Baumeister FA, Cianfarani S, et al.
A position effect on TRPS1 is associated with Ambras syndrome in humans and the Koala phenotype in mice. Hum Mol Genet 2008;17:3539-51.
[Figure 1], [Figure 2]