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CASE REPORT
Year : 2019  |  Volume : 64  |  Issue : 3  |  Page : 231-234
MORFAN syndrome: A rarity but a reality!


Department of Dermatology, Institute of Post Graduate Medical Education and Research and SSKM Hospital, Bhowanipore, Kolkata, West Bengal, India

Date of Web Publication20-May-2019

Correspondence Address:
Dr. Shreya Poddar
Flat No. 202, Rukmani Apartments, Near Chowk Thana, Jhauganj, Patna - 800 008, Bihar
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijd.IJD_160_19

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   Abstract 


Acanthosis nigricans (AN) describes clinically hyperpigmented skin, which most commonly affects the flexural areas such as axilla, groin and neck. It is usually a benign condition associated with obesity, insulin resistance, and hyperinsulinemia; endocrinopathy; or malignancy, in particular, gastrointestinal adenocarcinoma. It can also occur in association with various genetic syndromes involving various organ systems. Few such known syndromes are Berardinelli-Seip syndrome, Alström syndrome, Leprechaunism, and Bardet-Biedl syndrome. MORFAN syndrome, which associates mild mental retardation, pre- and post-natal overgrowth, remarkable facies and diffuse and widespread AN, is a rare entity.


Keywords: Acanthosis nigricans, MORFAN syndrome, pre and post-natal overgrowth


How to cite this article:
Roy G, Sen S, Poddar S. MORFAN syndrome: A rarity but a reality!. Indian J Dermatol 2019;64:231-4

How to cite this URL:
Roy G, Sen S, Poddar S. MORFAN syndrome: A rarity but a reality!. Indian J Dermatol [serial online] 2019 [cited 2019 Jun 27];64:231-4. Available from: http://www.e-ijd.org/text.asp?2019/64/3/231/258617





   Introduction Top


Acanthosis nigricans (AN) is a common dermatosis first described by Santi Unna and Monatsh Pollitzer in 1890. It is characterized by thick, hyperpigmented, verrucous plaques distributed at typical sites including mucous membranes.[1] AN is associated with multiple etiologic factors including direct autosomal transmission, genetic abnormalities, medication, malignancy, and endocrinological abnormalities.[2]

MORFAN is the acronym for a rare syndrome (M = Mild mental retardation, O = Pre and postnatal Overgrowth, RF = Remarkable Facies, AN = Acanthosis Nigricans).[2] Exact diagnostic criteria for MORFAN is lacking. Till date, only three cases have been reported worldwide.[3],[4],[5]

To the best of our knowledge no case has been reported from Asian subcontinent till date. Here, we report a case of a 10-year-old female fitting with the phenotypical features of MORFAN and give a comprehensive review of the other three similar cases [Table 1].
Table 1: A comparative tabulation between present case and the previous three reported cases

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   Case History Top


A 10-year-old Hindu girl, second issue, born out of non-consanguineous marriage presented to our OPD with complaints of gradually progressive, diffuse, velvety, blackish plaques over the neck, anterior part of the chest, bilateral cubital fossa, axilla, knuckles of fingers, and toes since 4 years of age. The intertriginous areas were affected the most [Figure 1]. The patient also complained of gradual weight gain and obesity since the same duration.
Figure 1: A 10-year-old girl of MORFAN syndrome with Acanthosis nigricans. Clinical image of axillary region showing black, velvety plaques

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There was no history of similar signs or symptoms in her elder female sibling or any near or distant family members. Her mother was hypothyroid. According to her mother, she was delivered prematurely at 34 weeks of gestation by normal vaginal delivery with a birth weight of 2.5 kg. She did have some respiratory distress for which she was given mask ventilation. There was no history of convulsion/seizure during her infancy or childhood. She had a history of suffering from recurrent respiratory infections and hypocalcemia during her childhood days.

Patient's mother took medical advice at 18 months of age for delayed developmental milestones. The child started standing with support at 3 years of age. The eruption of first tooth of the patient took place at 4 years of age. She started speaking mono and bi syllables at 5 and 6 years of age, respectively as noticed by her mother. Since last 2 years, the girl was often seen muttering to herself. Her mother also noticed that she could not compete socially or intellectually with children of her own age and hence underwent psychometric analysis [Place: Department of Applied Psychology, Calcutta University]. Her psychometric analysis at 8 years and 10 months revealed a social age of 5 years and 1 month and developmental age of 4 years and nine months denoting mild mental retardation.

The patient had started menstruating at 9 years of age. She has no control over her bladder. She was sent for Tanner breast staging that supported the impression of precocious puberty. She has been admitted to special education school for the last one and half years.

General examination revealed that her vitals were within normal limits. Anthropometric measurements revealed her weight to be 54 kg (>97 percentile) and height was 5 feet and 2 inches (>97 percentile). She also had large flat feet and large palms.

Mucocutaneous findings revealed diffuse, blackish, velvety pigmentation over the neck, anterior chest, bilateral cubital fossa, axilla, knuckles of fingers, and toes [Figure 2]. Oral and genital mucosa were not affected. Hair and nails were within normal limits.
Figure 2: Clinical image of diffuse, black pigmentation over neck and cubital fossa

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She had characteristic facial features with large, flat nose with depressed bridge of the nose. Her eyes were large, prominent, and protruding. She had puffy everted lips, large low lying ears, fleshy tongue with dental caries, and mixed dentition.

Routine laboratory investigations revealed mild anemia (Hb-10.6 g %). Liver function test, renal function test, fasting lipid profile were all within normal limit. Fasting glucose level was 58 mg/dl and fasting insulin level was 7 uIU/ml at the time of presentation. Thyroid profile and early morning cortisol level were within normal levels. Serum calcium level showed mild hypocalcemia (8.3 mg/dl). Radiological bone age revealed an age between 11 to 14 years [Figure 3]. USG abdomen, MRI/CT brain revealed no abnormality.
Figure 3: Radiological image of the child revealing a bone age of 11 to 14 years

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Genetic screening or mutation study could not be done because of lack of facility at our institution. A diagnosis of the rare MORFAN syndrome was made from the clinical findings.


   Discussion Top


MORFAN is a very rare syndrome.

The first case of MORFAN was reported by Seemanova et al. in 1993 of a 5-year-old boy who had mild mental retardation, pre- and post-natal overgrowth, facial anomalies, and AN.[3] They postulated that the patient had a genetic defect in insulin receptors according to his fasting as well as post-prandial glucose and insulin levels, which was perhaps the cause of AN, mental retardation, curly hair, and abnormal facies in this subject.

After 25 years, researchers reported a similar case with hypo-insulinemic hypoglycemia with distinct facies and other features consistent with MORFAN syndrome.[4] Whole exome sequencing revealed a mutation of the AKT2 gene. However, they failed to establish any relation of the mutation to MORFAN syndrome as similar mutations were also noted in other patients with hypo-insulinemic hypoglycemia.[4]

The third reported case was a 17-year-old female with diffuse AN, dysmorphic facies, developmental delay, and insulin resistance for which she had been receiving metformin.[5]

Our patient had diffuse long-standing AN, endomorphic body habitus, subtle facial features, and mild mental retardation consistent with the syndrome, but her fasting and post-prandial glucose and insulin levels were normal at the time of presentation. AN has a multifactorial etiology such as direct autosomal transmission, medications, endocrinopathy, malignancies, and genetic abnormalities. Unfortunately, a genetic screening or mutation study could not be performed. She also had persistent hypocalcemia, precocious puberty, and accelerated skeletal growth.

The genetic and molecular basis of this syndrome still somehow remains a mystery, hence no treatment algorithm also exists apart from symptomatic management. We hope that complete physical, biochemical, and genetic screening is pursued in cases fitting the above phenotype to better identify the syndrome and elucidate its pathogenesis. MORFAN is not a myth but a fact.


   Conclusion Top


MORFAN is an extremely rare syndrome with three cases reported worldwide till date as per data available with an exhaustive search on the internet with keyword MORFAN. No algorithm exists to identify MORFAN as of today and more reports of rare cases such as ours will aid in forming a criterion.

Lack of genetic studies is a drawback in our patient. We report this disorder to increase awareness about the existence of such a rare syndrome.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patient understood that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Schwartz RA. Acanthosis nigricans. J Am Acad Dermatol 1994;31:1-19.  Back to cited text no. 1
    
2.
Inamdar AC, Palit A. Generalized acanthosis nigricans in childhood. Pediatr Dermatol 2004;21:277-9.  Back to cited text no. 2
    
3.
Seemanová E, Rüdiger HW, Dreyer M. Morfan: A new syndrome characterized by mental retardation, pre-and postnatal overgrowth, remarkable face and acanthosis nigricans in 5-year-old boy. Am J Med Genet 1993;45:525-8.  Back to cited text no. 3
    
4.
Garg N, Bademci G, Foster J II, Sıklar Z, Berberoglu M, Tekin M. MORFAN syndrome: An infantile hypoinsulinemic hypoketotic hypoglycemia due to an AKT2 mutation. J Pediatr 2015;167:489-91.  Back to cited text no. 4
    
5.
Bryan Hiscox, Jenny Hu, Lorraine C Young. A case of MORFAN syndrome. Cutis 2015;95:E20-1.  Back to cited text no. 5
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1]



 

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    Abstract
   Introduction
   Case History
   Discussion
   Conclusion
    References
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