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Year : 2017  |  Volume : 2  |  Issue : 4  |  Page : 58-62

Sporadic association of Legg–Calve–Perthes disease with rare phakomatoses-Gomez-Lopez-Hernandez syndrome

Department of Orthopedics, Government Medical College, Kozhikkode, Kerala, India

Date of Web Publication9-Nov-2017

Correspondence Address:
Balaji Zacharia
Department of Orthopedics, Government Medical College, Kozhikkode, Kerala
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijssr.ijssr_9_17

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Gomez-Lopez-Hernandez syndrome (GLH) is a very rare phakomatosis, which is characterized by the triad of rhombencephalosynapsis, facial anesthesia in the trigeminal area, and scalp alopecia. A 9-year-old boy with pain and limping right hip for 6 months was presented. Clinically, he was having bilateral symmetrical temporal alopecia, strabismus, and pseudoproptosis. Magnetic resonance imaging brain shows cerebellar fusion. Examination of the hip was consistent with the diagnosis of Perthes disease. Even though some of the phakomatoses are associated with skeletal abnormalities, there is no association of any phakomatoses with Legg–Calve–Perthes disease (LCPD) of the hip. This will be the first ever report of an association of GLH syndrome with LCPD.

Keywords: Cerebellotrigeminal dermal dysplasia, Gomez-Lopez-Hernandez syndrome, Legg–Calve–Perthes disease, phakomatoses

How to cite this article:
Zacharia B, Sherule M T, Subramaniam D, Purushothaman R. Sporadic association of Legg–Calve–Perthes disease with rare phakomatoses-Gomez-Lopez-Hernandez syndrome. IJS Short Rep 2017;2:58-62

How to cite this URL:
Zacharia B, Sherule M T, Subramaniam D, Purushothaman R. Sporadic association of Legg–Calve–Perthes disease with rare phakomatoses-Gomez-Lopez-Hernandez syndrome. IJS Short Rep [serial online] 2017 [cited 2019 Jan 16];2:58-62. Available from: http://www.ijsshortreports.com/text.asp?2017/2/4/58/217927

  Introduction Top

Phakomatoses (or neuro-oculo-cutaneous syndromes) are multisystem disorders that have characteristic central nervous system, ocular, and cutaneous lesions of variable severity. It is due to the common ectodermal origin of skin and brain tissues.[1] Conditions such as neurofibromatosis, tuberous sclerosis, ataxia telangiectasia, and Sturge-Weber syndrome are few common phakomatoses.[2] Phakomatoses can be due to genetic or acquired disease that can affect both brain and skin tissues. Von Hippel-Lindau disease is one phakomatosis with very minimal skin manifestation.[3]

Gomez-Lopez-Hernandez syndrome (GLH) is a rare neurocutaneous (phakomatoses) disorder affecting the trigeminal nerve, brain tissue, and scalp. This syndrome was first described by Gomez in 1979 in a girl. There are very few diagnostic cases of GLH syndrome.[4] According to de Mattos et al., there are only 34 diagnostic cases of GLH.[5] Most cases are reported from Brazil and other South American countries. GLH is characterized by rhombencephalosynapsis, bilateral temporal alopecia, and ocular manifestation and therefore is also known as cerebellotrigeminal dermal dysplasia.[4] The disease is also characterized by brachycephaly, thin lips, and low-set and posterior-angled ears. Hypertelorism, strabismus, clouding of the cornea, loss of stimulation when stimulus is given, and low motor control are also seen in some cases of GLH. Rhombencephalosynapsis and bilateral parietal alopecia are the most consistent features of GLH.[6],[7] People with GLH have shown moderate-to-severe intellectuality, hypotonia, hydrocephalus, and reduced or agenesis of the corpus callosum.[8] Magnetic resonance imaging (MRI) brain of every patient with GLH syndrome has shown fusion of the cerebellar hemisphere and absence of the cerebellar vermis.[9],[10]

The exact cause of GLH is unknown. It is proposed that it may be due to ASP2 gene. Lack of expression from the WNT1, FGF8, FGF17, OTX2, fgf8, and fgf17 genes has been implicated as possible cause of cerebellum fusion.[10] de Mattos also suggests recessive mode of inheritance. The diagnosis of GLH is mainly based on clinical features. The management is similar to any other disease affecting the development of the brain as there is no cure for the disease.

We are presenting the case of a 9-year-old boy, who was presented with limping and pain of the right hip. Clinical examination findings are consistent with Legg–Calve–Perthes disease (LCPD). We are presenting this case as there is no reported case of GLH with skeletal anomaly other than skull anomaly in the whole of English biomedical literature. We had to do an arthrodiastasis followed by varus derotational osteotomy for containment of this hip. The association of GLH with Perthes disease did not have any impact on outcome.

  Case Report Top

A 9-year-old boy was presented with limping and hip pain for the past 6 months. He is the first born child of nonconsanguinous marriage and belongs to low socioeconomic status. He shows delayed motor milestone and below average school performance. On examination, he presented with brachycephaly, bilateral triangular symmetrical area of alopecia in the temporal region [Figure 1], low-set ears, hypertelorism, strabismus, shallow orbit with pseudoproptosis, corneal anesthesia [Figure 2], simian crease on the right hand, and high-arched palate.
Figure 1: Lateral profile of the head showing temporal alopecia and low-set ears

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Figure 2: (a and b) Pseudoproptosis with hypertelorism and corneal anesthesia

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He is short for his age. The right lower limb was shortened and externally rotated. The greater trochanter was thickened, irregular, and at higher level compared to opposite side. There is fixed flexion deformity of 20° with further flexion up to 120° with further flexion restricted due to pain and spasm. Abduction and internal rotation is restricted. There is 1 cm shortening. Trendelenburg's sign was positive with Trendelenburg gait [Figure 3].
Figure 3: Decreased abduction, internal rotation, and positive Trendelenburg's sign of the right hip

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In view of the above clinical findings, we took opinion from the pediatrics, dermatology, ophthalmology, and neuromedicine specialties. They pointed to the possibility of phakomatoses. Computer tomography of the head showed fusion of the cerebellar hemisphere. MRI [Figure 4] of the brain shows absent cerebellar vermis with fusion of the bilateral cerebellar hemisphere and prominent interthalamic adhesion suggestive of rhombencephalosynapsis. The clinical findings and MRI brain are consistent with GLH syndrome.
Figure 4: Computed tomography head showing fusion of cerebellar fusion and magnetic resonance imaging of the brain showing absent cerebellar vermis with fusion of bilateral cerebellar hemisphere and prominent interthalamic adhesion

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The radiograph of the hip [Figure 5] was showing avascular necrosis of capital femoral epiphysis on the right side with multiple areas of sclerosis and lysis, probably in fragmentation stage. There are lateral subluxation, horizontal growth plate, diffuse metaphyseal reaction, and Gage's sign (head-at-risk sign) of Perthes disease. MRI right hip [Figure 6] shows features of flattening of the right femoral head with irregular surface contour and loss of volume. Femoral head appears sclerotic with loss of signal intensity in all sequences. Few irregular ovoid cystic foci are noted in the femoral metaphyseal region. Clinically and radiologically, the findings are consistent with Perthes disease. The ethical committee clearance and informed written consent were obtained. We have treated the child with arthrodiastasis for remodeling of femoral capital epiphysis followed by varus derotational osteotomy [Figure 7] for containment of the head. After 12-month follow-up, the child is doing well with range of movements nearing normal in all planes.
Figure 5: Radiograph shows Perthes disease of the right hip

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Figure 6: Magnetic resonance imaging hip shows flattening of femoral epiphysis with irregular contour and sclerotic foci of the right hip

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Figure 7: Radiograph showing arthrodiastasis of the right hip, after orthofix removal, after varus derotational osteotomy

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  Discussion Top

Phakomatoses are rare congenital disease due to abnormal development of ectoderm, affecting brain, and cutaneous tissues. Even though there is no association with mesodermal development, certain skeletal abnormalities are seen in association in with certain phakomatosis such as limb-length discrepancy, scoliosis, spinal dysraphism, hemihypertrophy, syndactyly, and premature eruption of the teeth.[11] In 2008, Ching Wu et al. reported a case of phakomatosis cesioflammea associated with pectus excavatum.[12] Neurofibromatosis is associated with spinal deformities, widening of neural foramen, and intraspinal neurofibromas. It is also associated with tibial dysplasia.[13],[14]

GLH is a very rare phakomatosis described by Gomez in 1979 and later by Lopez Hernandez in 1982.[15],[16] The exact etiology of this condition is unknown, and there is no gender predilection. Most cases are sporadic.[8] Even though several brain anomalies are associated with it, the most characteristic feature is the dorsal fusion of the cerebellar hemisphere. Other anomalies include hypogenesis of the vermis, fusion of the dentate nuclei, and superior cerebellar peduncles. Ventriculomegaly (hydrocephaly), absent septum pellucidum, and hypoplastic corpus callosum are also seen in GLH.[17],[18] The clinical feature of GLH can vary considerably in severity. The typical alopecia in GLH is bilateral symmetrical band-like involvement in the parietal region.[19] Typically, the ophthalmic branch of trigeminal nerve is involved in this condition. Even though a few patients with normal cognitive function in GLH have been reported, most of the cases are having mental retardation.[20] Neuropsychiatric symptoms such as depression, bipolar disorder, obsessive compulsive disorder, and suicidal tendency are reported in isolated rhombencephalosynapsis and also in GLH.[6],[21]

GLH is not associated with any other diseases. However, one case of growth hormone deficiency was reported along with GLH.[21]

LCPD is a self-limiting condition characterized by loss of blood supply to the growing capital femoral epiphysis followed by revascularization and remodeling.[22] The risk factors for the development of Perthes disease are low socioeconomic status, delayed skeletal maturity, low birth weight, short stature, and systemic hormonal changes.[23] Children with LCPD usually present with painless limping and feature of coxa vara with thickened and elevated trochanter. It usually affects boys in the age group of 4–12 years. There is no association between LCPD and any other phakomatosis described in the whole of the English biomedical literature. The sporadic association of Perthes disease and trichorhinophalangeal syndrome is published.[24]

We presented the case of a 9-year-old boy with pain and limping on the right hip of 6-month duration. The orthopedic examination of his right hip is consistent with Perthes disease. The general, ophthalmic, and neurological examinations, including MRI studies, are diagnostic of GLH syndrome. This is the first ever reported case of any phakomatosis with LCPD and the first ever association of GLH with Perthes disease with clinical and radiological features suggestive of Perthes disease. To the best of our knowledge, no case has been reported earlier, associating Perthes disease with phakomatoses.

  Conclusion Top

LCPD is a common pediatric hip problem in our part of the world – south western part of India. GLH syndrome is a rare variety of phakomatoses. Most of the cases are reported from South America. No single case of GLH syndrome has been reported from our part of the world. Moreover, association of Perthes disease with no phakomatoses has been reported ever. Even though there was some difficulty in getting containment of the hip, the association of GLH with Perthes disease did not have any impact on outcome.

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 patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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Yanoff M, Duker JS. Ophthalmology. Philadelphia: Elsevier Health Sciences; 2009. p. 937.  Back to cited text no. 2
GE. Phakomatosis Medcyclopaedia. Archived from the Original on 2012-02-05.  Back to cited text no. 3
Fernández-Jaén A, Fernández-Mayoralas DM, Calleja-Pérez B, Muñoz-Jareño N, Moreno N. Gomez-Lopez-Hernandez syndrome: Two new cases and review of the literature. Pediatr Neurol 2009;40:58-62.  Back to cited text no. 4
de Mattos VF, Graziadio C, Machado Rosa RF, Lenhardt R, Alves RP, Trevisan P, et al. Gómez-López-Hernández syndrome in a child born to consanguineous parents: New evidence for an autosomal-recessive pattern of inheritance? Pediatr Neurol 2014;50:612-5.  Back to cited text no. 5
Gomy I, Heck B, Santos AC, Figueiredo MS, Martinelli CE Jr. Nogueira MP, et al. Two New Brazilian patients with Gómez-López-Hernández syndrome: Reviewing the expanded phenotype with molecular insights. Am J Med Genet A 2008;146A:649-57.  Back to cited text no. 6
Sukhudyan B, Jaladyan V, Melikyan G, Schlump JU, Boltshauser E, Poretti A, et al. Gómez-lópez-hernández syndrome: Reappraisal of the diagnostic criteria. Eur J Pediatr 2010;169:1523-8.  Back to cited text no. 7
Poretti A, Bartholdi D, Gobara S, Alber FD, Boltshauser E. Gomez-lopez-hernandez syndrome: An easily missed diagnosis. Eur J Med Genet 2008;51:197-208.  Back to cited text no. 8
Abdel-Salam GM, Abdel-Hadi S, Thomas MM, Eid OM, Ali MM, Afifi HH, et al. Gómez-López-Hernández syndrome versus rhombencephalosynapsis spectrum: A rare co-occurrence with bipartite parietal bone. Am J Med Genet A 2014;164A: 480-3.  Back to cited text no. 9
Choudhri AF, Patel RM, Wilroy RS, Pivnick EK, Whitehead MT. Trigeminal nerve agenesis with absence of foramina rotunda in Gómez-López-Hernández syndrome. Am J Med Genet A 2015;167A: 238-42.  Back to cited text no. 10
Fernández-Guarino M, Boixeda P, de Las Heras E, Aboin S, García-Millán C, Olasolo PJ, et al. Phakomatosis pigmentovascularis: Clinical findings in 15 patients and review of the literature. J Am Acad Dermatol 2008;58:88-93.  Back to cited text no. 11
Wu CY, Chen PH, Chen GS. Phacomatosis cesioflammea associated with pectus excavatum. Acta Derm Venereol 2009;89:309-10.  Back to cited text no. 12
Hsu LC, Lee PC, Leong JC. Dystrophic spinal deformities in neurofibromatosis. Treatment by anterior and posterior fusion. J Bone Joint Surg Br 1984;66:495-9.  Back to cited text no. 13
Kumarmeena R, Arun Kumar GC, Nongthon Singh S, Nepram S. Congenital pseudoarthrosis of the tibia: A case report. IOSR J Dent Med Sci 2013;3:21-2.  Back to cited text no. 14
Gomez MR. Cerebellotrigeminal and focal dermal dysplasia: A newly recognized neurocutaneous syndrome. Brain Dev 1979;1:253-6.  Back to cited text no. 15
López-Hernández A. Craniosynostosis, ataxia, trigeminal anaesthesia and parietal alopecia with pons-vermis fusion anomaly (atresia of the fourth ventricle). Report of two cases. Neuropediatrics 1982;13:99-102.  Back to cited text no. 16
Toelle SP, Yalcinkaya C, Kocer N, Deonna T, Overweg-Plandsoen WC, Bast T, et al. Rhombencephalosynapsis: Clinical findings and neuroimaging in 9 children. Neuropediatrics 2002;33:209-14.  Back to cited text no. 17
Truwit CL, Barkovich AJ, Shanahan R, Maroldo TV. MR imaging of rhombencephalosynapsis: Report of three cases and review of the literature. AJNR Am J Neuroradiol 1991;12:957-65.  Back to cited text no. 18
Purvis DJ, Ramirez A, Roberts N, Harper JI. Gomez-lopez-hernandez syndrome: Another consideration in focal congenital alopecia. Br J Dermatol 2007;157:196-8.  Back to cited text no. 19
Muñoz R MV, Santos AC, Graziadio C, Pina-Neto JM. Cerebello-trigeminal-dermal dysplasia (Gómez-López-Hernández syndrome): Description of three new cases and review. Am J Med Genet 1997;72:34-9.  Back to cited text no. 20
Brocks D, Irons M, Sadeghi-Najad A, McCauley R, Wheeler P. Gomez-Lopez-Hernandez syndrome: Expansion of the phenotype. Am J Med Genet 2000;94:405-8.  Back to cited text no. 21
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Bahmanyar S, Montgomery SM, Weiss RJ, Ekbom A. Maternal smoking during pregnancy, other prenatal and perinatal factors, and the risk of Legg-Calvé-Perthes disease. Pediatrics 2008;122:e459-64.  Back to cited text no. 23
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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]


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