Case report
Rare skeletal abnormalities in Rothmund–Thomson syndrome: a case report Krishnarao V. Pasagadugula, MD, Teja Chennamsetty, MBBS, Krishnaveni Avvaru, MD, and Kavya Chennamsetty, MD
Department of Dermatology, Andhra Medical College, Visakhapatnam, Andhra Pradesh, India Correspondence Krishnarao V. Pasagadugula, MD 50-121-63/1 BS layout Visakhapatnam 530013 Andhra Pradesh, India E-mail: [email protected] Conflicts of interest: None. doi: 10.1111/ijd.12723
Introduction Rothmund–Thomson syndrome (RTS) is a rare autosomal recessive photosensitive genodermatosis1–3 characterized by poikilodermatous skin rash, short stature, and premature aging.3–5 Two types were described and in type 2 RTS, congenital bone defects with an increased risk of osteosarcoma were reported.3,5 Few studies focused on visible osseous changes such as frontal bossing, saddle nose, and absence of the thumb.3,6–8 Other reports showed long bone defects, including radial ray defects.6,7 In a small set of patients with RTS, dental anomalies, nail dystrophy, and palmoplantar hyperkeratosis were described.3,4,9 Few conditions having poikilodermatous skin changes such as Kindlers’, Bloom’s, and Werner’s syndromes should be considered under differential diagnosis.3 Treatment includes sun protection and surgical removal of cataracts as and when they were detected.3,4,10,11 As an extension to the existing spectrum of skeletal features, we report a case of RTS with rare osseous abnormalities. Case report A 4-year-old boy, born to healthy parents with a history of consanguinity, was brought to the outpatient Department of Dermatology, Andhra Medical College (Visakhapatnam, Andhra Pradesh, India), with complaints of redness and rash over the face, arms, and upper trunk
of two years’ duration. There was a history of delayed milestones and recurrent vomiting and diarrhea. Skin was normal at birth. From the age of two years, his mother noticed episodes of rash with swelling and small blisters over the face following exposure to sunlight. On physical examination, diffuse erythema with mottled pigmentation and atrophy was seen on the face (Fig. 1), arms, and V of the neck. Features such as frontal bossing, depressed nasal bridge, and small chin were noticed. His ears were normal. Scalp hair was sparse and blonde. His eyebrows and eyelashes were scanty (Fig. 2). Teeth and nails were normal. Genital examination showed retracted prepuce and empty scrotal sac on the left side. Examination of hands (Figs. 3 and 4) and feet showed bilateral absence of the little finger and absence of the third toe of the right foot. There was a deep cleft between the second and fourth toes extending up to the junction of the distal third to middle third of the right foot (Fig. 7). Digital x-rays of both hands showed absence of the fifth metacarpal and phalanges of the fifth finger bilaterally with normal bone density (Figs. 5 and 6). X-ray of the right foot showed absence of the third metatarsal and phalanges of the third toe, and a single tarsal bone with normal bone density (Fig. 8). Skull x-ray showed increased anteroposterior diameter (dolicho-cephaly) (Fig. 9). Hematological examination revealed no abnormalities except microcytic hypochromic anemia with reactive lymphocytosis. Ultrasound examination of the abdomen showed hypo1
ª 2014 The International Society of Dermatology
International Journal of Dermatology 2014
2
Case report
Rothmund-Thomson syndrome: a case report
Pasagadugula et al.
Figure 4 Absence of little finger (right hand)
Figure 1 Poikilodermatous features
plastic left testis at the deep inguinal ring. Examination of other systems such as eyes, respiratory, cardiovascular, and central nervous system revealed no abnormalities. Discussion Rothmund–Thomson syndrome is a rare autosomal recessive genodermatosis. The features described by Rothmund and Thomson such as poikilodermatous skin rash and osseous deformities were seen in our case, and in our
Figure 2 Bird-like facies
Figure 3 Absence of little finger (left hand) International Journal of Dermatology 2014
Figure 5 X-ray showing absence of metacarpal and phalanges of little finger ª 2014 The International Society of Dermatology
Pasagadugula et al.
Rothmund-Thomson syndrome: a case report
Case report
Figure 8 X-ray right foot showing absence of middle toe and third metatarsal and phalanges (right foot)
Figure 6 Absence of metacarpal and phalnges of left fifth
finger
Figure 9 Dolicocephalic skull
Figure 7 Bifid right foot ª 2014 The International Society of Dermatology
case, features such as sparse scalp hair and scanty eyebrows and eyelashes were in concurrence with a study done by Wang et al.10 Dental anomalies, nail abnormalities, and plantar hyperkeratosis reported by Popadic et al. and Larizza et al.3,9 were not seen in our case. Gastrointestinal disturbances such as chronic emesis and diarrhea during childhood reported earlier by other authors4,12 were present in our case. Myelodysplasia and leukemia, described8 earlier, were not seen in our case except for microcytic hypochromic anemia with reactive lymphocytosis. The incidence of skeletal abnormalities in RTS varies between 68 and 75% and includes broad clinical and radiological abnormalities.7 Previously undescribed features such as absence of the little finger of both hands International Journal of Dermatology 2014
3
4
Case report
Rothmund-Thomson syndrome: a case report
and absence of the right middle toe presenting as a bifid foot were seen in our case. Conclusion Hence, we are reporting this case of RTS with ulnar ray defects and bifid right foot. These rare skeletal features may be considered as an extension to the existing spectrum of skeletal abnormalities in RTS. References 1 Wang LL, Gannavarapu A, Kozinetz CA, et al. Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund Thomson syndrome. J Natl Cancer Inst 2003; 95: 669–674. 2 Wolff K, Goldsmith L, Katz S, et al. Fitzpatrick’s Textbook of Dermatology in General Medicine, 2 vols, 7th edn. New York, NY: McGraw-Hill Professional, 2007. 3 Larizza L, Roversi G, Volpi L. Rothmund-Thomson syndrome. Orphanet J Rare Dis 2010; 5: 1–16. 4 Wang LL, Plon SE. Rothmund-Thomson syndrome. In: Pagon RA, Adam MP, Ardinger HH, et al, eds. Gene Reviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2014.
International Journal of Dermatology 2014
Pasagadugula et al.
5 Cafardi JA. Rothmund-Thomson syndrome. The Manual of Dermatology. London: Springer-New Delhi, 2013: 97– 99. 6 Bolognia JL. Textbook of Dermatology, 2nd edn. St. Louis, MO: Elsevier Publishers, 2008 7 Mehollin-Ray AR, Kozinetz CA, Schlesinger AE, et al. Radiographic abnormalities in Rothmund-Thomson syndrome and genotype-phenotype correlation with RECQL4 mutation status. AJR Am J Roentgenol 2008; 191: 62–66. 8 Pencovich N, Margalit N, Constantini S. Atypical meningoma as a solitary malignancy in a patient with Rothmund-Thomson syndrome. Surg Neurol Int 2013; 3: 148. 9 Popadic S, Nikolic M, Gajic-Veljic M, et al. Rothmund-Thomson syndrome the first case with plantar keratoderma and the second with celiac disease. Acta Dermatovenerol Alp Panonica Adriat 2006; 15: 90–93. 10 Wang LL, Levy ML, Lewis RA, et al. Clinical manifestations in a cohort of 41 Rothmund-Thomson syndrome patients. Am J Med Genet 2001; 102: 11–17. 11 Moschella SL, Hurley HJ. Textbook of Dermatology, 3rd edn, Vol. 2. Philadelphia: Saunders Publishers. 12 Hicks MJ, Roth JR, Kozinetz CA, et al. Clinic pathologic features of osteosarcoma in patients with RothmundThomson syndrome. J Clin Oncol 2007; 25: 370–375.
ª 2014 The International Society of Dermatology
Rare skeletal abnormalities in Rothmund–Thomson syndrome: a case report Krishnarao V. Pasagadugula, MD, Teja Chennamsetty, MBBS, Krishnaveni Avvaru, MD, and Kavya Chennamsetty, MD
Department of Dermatology, Andhra Medical College, Visakhapatnam, Andhra Pradesh, India Correspondence Krishnarao V. Pasagadugula, MD 50-121-63/1 BS layout Visakhapatnam 530013 Andhra Pradesh, India E-mail: [email protected] Conflicts of interest: None. doi: 10.1111/ijd.12723
Introduction Rothmund–Thomson syndrome (RTS) is a rare autosomal recessive photosensitive genodermatosis1–3 characterized by poikilodermatous skin rash, short stature, and premature aging.3–5 Two types were described and in type 2 RTS, congenital bone defects with an increased risk of osteosarcoma were reported.3,5 Few studies focused on visible osseous changes such as frontal bossing, saddle nose, and absence of the thumb.3,6–8 Other reports showed long bone defects, including radial ray defects.6,7 In a small set of patients with RTS, dental anomalies, nail dystrophy, and palmoplantar hyperkeratosis were described.3,4,9 Few conditions having poikilodermatous skin changes such as Kindlers’, Bloom’s, and Werner’s syndromes should be considered under differential diagnosis.3 Treatment includes sun protection and surgical removal of cataracts as and when they were detected.3,4,10,11 As an extension to the existing spectrum of skeletal features, we report a case of RTS with rare osseous abnormalities. Case report A 4-year-old boy, born to healthy parents with a history of consanguinity, was brought to the outpatient Department of Dermatology, Andhra Medical College (Visakhapatnam, Andhra Pradesh, India), with complaints of redness and rash over the face, arms, and upper trunk
of two years’ duration. There was a history of delayed milestones and recurrent vomiting and diarrhea. Skin was normal at birth. From the age of two years, his mother noticed episodes of rash with swelling and small blisters over the face following exposure to sunlight. On physical examination, diffuse erythema with mottled pigmentation and atrophy was seen on the face (Fig. 1), arms, and V of the neck. Features such as frontal bossing, depressed nasal bridge, and small chin were noticed. His ears were normal. Scalp hair was sparse and blonde. His eyebrows and eyelashes were scanty (Fig. 2). Teeth and nails were normal. Genital examination showed retracted prepuce and empty scrotal sac on the left side. Examination of hands (Figs. 3 and 4) and feet showed bilateral absence of the little finger and absence of the third toe of the right foot. There was a deep cleft between the second and fourth toes extending up to the junction of the distal third to middle third of the right foot (Fig. 7). Digital x-rays of both hands showed absence of the fifth metacarpal and phalanges of the fifth finger bilaterally with normal bone density (Figs. 5 and 6). X-ray of the right foot showed absence of the third metatarsal and phalanges of the third toe, and a single tarsal bone with normal bone density (Fig. 8). Skull x-ray showed increased anteroposterior diameter (dolicho-cephaly) (Fig. 9). Hematological examination revealed no abnormalities except microcytic hypochromic anemia with reactive lymphocytosis. Ultrasound examination of the abdomen showed hypo1
ª 2014 The International Society of Dermatology
International Journal of Dermatology 2014
2
Case report
Rothmund-Thomson syndrome: a case report
Pasagadugula et al.
Figure 4 Absence of little finger (right hand)
Figure 1 Poikilodermatous features
plastic left testis at the deep inguinal ring. Examination of other systems such as eyes, respiratory, cardiovascular, and central nervous system revealed no abnormalities. Discussion Rothmund–Thomson syndrome is a rare autosomal recessive genodermatosis. The features described by Rothmund and Thomson such as poikilodermatous skin rash and osseous deformities were seen in our case, and in our
Figure 2 Bird-like facies
Figure 3 Absence of little finger (left hand) International Journal of Dermatology 2014
Figure 5 X-ray showing absence of metacarpal and phalanges of little finger ª 2014 The International Society of Dermatology
Pasagadugula et al.
Rothmund-Thomson syndrome: a case report
Case report
Figure 8 X-ray right foot showing absence of middle toe and third metatarsal and phalanges (right foot)
Figure 6 Absence of metacarpal and phalnges of left fifth
finger
Figure 9 Dolicocephalic skull
Figure 7 Bifid right foot ª 2014 The International Society of Dermatology
case, features such as sparse scalp hair and scanty eyebrows and eyelashes were in concurrence with a study done by Wang et al.10 Dental anomalies, nail abnormalities, and plantar hyperkeratosis reported by Popadic et al. and Larizza et al.3,9 were not seen in our case. Gastrointestinal disturbances such as chronic emesis and diarrhea during childhood reported earlier by other authors4,12 were present in our case. Myelodysplasia and leukemia, described8 earlier, were not seen in our case except for microcytic hypochromic anemia with reactive lymphocytosis. The incidence of skeletal abnormalities in RTS varies between 68 and 75% and includes broad clinical and radiological abnormalities.7 Previously undescribed features such as absence of the little finger of both hands International Journal of Dermatology 2014
3
4
Case report
Rothmund-Thomson syndrome: a case report
and absence of the right middle toe presenting as a bifid foot were seen in our case. Conclusion Hence, we are reporting this case of RTS with ulnar ray defects and bifid right foot. These rare skeletal features may be considered as an extension to the existing spectrum of skeletal abnormalities in RTS. References 1 Wang LL, Gannavarapu A, Kozinetz CA, et al. Association between osteosarcoma and deleterious mutations in the RECQL4 gene in Rothmund Thomson syndrome. J Natl Cancer Inst 2003; 95: 669–674. 2 Wolff K, Goldsmith L, Katz S, et al. Fitzpatrick’s Textbook of Dermatology in General Medicine, 2 vols, 7th edn. New York, NY: McGraw-Hill Professional, 2007. 3 Larizza L, Roversi G, Volpi L. Rothmund-Thomson syndrome. Orphanet J Rare Dis 2010; 5: 1–16. 4 Wang LL, Plon SE. Rothmund-Thomson syndrome. In: Pagon RA, Adam MP, Ardinger HH, et al, eds. Gene Reviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2014.
International Journal of Dermatology 2014
Pasagadugula et al.
5 Cafardi JA. Rothmund-Thomson syndrome. The Manual of Dermatology. London: Springer-New Delhi, 2013: 97– 99. 6 Bolognia JL. Textbook of Dermatology, 2nd edn. St. Louis, MO: Elsevier Publishers, 2008 7 Mehollin-Ray AR, Kozinetz CA, Schlesinger AE, et al. Radiographic abnormalities in Rothmund-Thomson syndrome and genotype-phenotype correlation with RECQL4 mutation status. AJR Am J Roentgenol 2008; 191: 62–66. 8 Pencovich N, Margalit N, Constantini S. Atypical meningoma as a solitary malignancy in a patient with Rothmund-Thomson syndrome. Surg Neurol Int 2013; 3: 148. 9 Popadic S, Nikolic M, Gajic-Veljic M, et al. Rothmund-Thomson syndrome the first case with plantar keratoderma and the second with celiac disease. Acta Dermatovenerol Alp Panonica Adriat 2006; 15: 90–93. 10 Wang LL, Levy ML, Lewis RA, et al. Clinical manifestations in a cohort of 41 Rothmund-Thomson syndrome patients. Am J Med Genet 2001; 102: 11–17. 11 Moschella SL, Hurley HJ. Textbook of Dermatology, 3rd edn, Vol. 2. Philadelphia: Saunders Publishers. 12 Hicks MJ, Roth JR, Kozinetz CA, et al. Clinic pathologic features of osteosarcoma in patients with RothmundThomson syndrome. J Clin Oncol 2007; 25: 370–375.
ª 2014 The International Society of Dermatology
