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Skeletal dysplasia with unusual visceral manifestations

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Skeletal dysplasia with unusual visceral manifestations

Q1: What is the diagnosis?

The diagnosis is pycnodysostosis, which is a rare form of skeletal dysplasia characterised by moderate and generalised osteosclerosis. The diagnosis is based on clinical features and radiological findings. The cardinal features are short stature, large open fontanelles (the fontanelles may remain open even in adulthood), an obtuse mandibular angle, dysplastic clavicles, and hypoplastic/aplastic distal phalanges. Radiography of the bones show generalised and uniform hyperdensity and marked obliteration of the medullary cavity.

Q2: What is the most important differential diagnosis?

The most important differential diagnosis is osteopetrosis tarda, which is also called Albers-Schonberg disease. This disorder is characterised by severe generalised osteosclerosis, anaemia due to bone marrow failure, and hepatosplenomegaly due to extramedullary erythropoiesis. Neurological deficits like deafness, blindness, and cranial nerve palsies are common due to bony sclerosis. Radiography of the bones shows no medullary cavity. But short stature, open fontanelles, clavicular dysplasia, and distal phalangeal hypoplasia/aplasia are not seen in osteopetrosis tarda.

Q3: What complications can be anticipated in this case?

In most cases of pycnodysostosis there is adequate bone marrow function with no anaemia or hepatosplenomegaly. The life span is normal. But this case has atypical features that are usually seen in osteopetrosis tarda. These atypical features—namely, anaemia, splenohepatomegaly, and papilloedema—will require close clinical monitoring. The anticipated complications are bone marrow failure, hypersplenism, and optic atrophy. Also other neurological deficits due to ongoing bony sclerosis like deafness and cranial nerve palsies are to be watched for. Lastly, the child may develop transverse bone fractures and obstructive sleep apnoea, which are known complications in a typical case of pycnodysostosis.


Pycnodysostosis was first described by Maroteaux and Lamy in 1962. The word pycnodysostosis is of Greek origin (“pycnos” means dense or thick, “dys” means defective and “ostosis” means bone).1 The inheritance of pycnodysostosis is believed to be autosomal recessive. The diagnosis rests on clinical and radiological features.2–4 The exact incidence of pycnodysostosis is not known. Until 1988, 78 cases had been reported.5 The reported male to female occurrence is 1:1.

The characteristic features of this rare syndrome include short stature, a large head with open fontanelles (often remaining open in adulthood), separated sutures, an obtuse or absent mandibular angle, under developed facial bones, dysplastic clavicles, and hypoplasia or aplasia of distal phalanges.2,3 The osteolysis of distal phalanges may progressively become more severe. The teeth are malformed, hypoplastic, malpositioned, and prone to caries. Deciduous teeth may persist into adulthood giving rise to a double row of teeth. Trunk deformities like kyphosis, scoliosis, and a narrow chest may be seen. There is a tendency for multiple transverse fractures with minimal trauma in the long bones of lower limbs, metatarsals, clavicles, and mandible. These fractures can occur at any age, are usually self limited, but may lead to deformities. Other features include bilateral proptosis, a long uvula, obstructive sleep apnoea, and a blue sclera. Most cases have a normal intelligence.2,3 The most consistent radiological feature is moderate generalised osteosclerosis. The osteosclerosis in long bones is most prominent proximally.2

A close differential diagnosis of pycnodysostosis is osteopetrosis tarda (Albers-Schonberg disease) or the benign dominant variety of osteopetrosis, but there are distinct differentiating features. Osteopetrosis tarda occurs in 1:100 000 live births; the reported male: female ratio is 1:1.6 In osteopetrosis tarda, the inheritance is autosomal dominant in most cases and autosomal recessive in a few; also stunted growth and open fontanelles, clavicular dysplasia, and distal phalangeal hypoplasia are not seen.4 Osteopetrosis tarda is characterised by progressive obliteration of the bone marrow due to formation of new bone, as there is failure of osteoclasts to resorb bone matrix. Progressive anaemia due to bone marrow failure and splenohepatomegaly due to extramedullary erythropoeisis are common findings. Hypersplenism may ensue, leading to pancytopenia.7 Leucoerythroblastosis is found with crowding of cells out of the marrow prematurely (myelophthisis). Deafness, blindness, and neurological deficits due to bony sclerosis are common.7 There is hypotubulation of the ends of shafts of bones with alternating lines of increased and decreased bone density; a finding never found in pycnodysostosis.

It was earlier believed that pycnodysostosis is not associated with anaemia and splenohepatomegaly.2 However a few cases of pycnodysostosis with visceral and haematological manifestations have been described.4,5,8–10

The child reported here had classical clinical and radiological findings of pycnodysostosis along with atypical features like splenohepatomegaly, anaemia, and thrombocytopenia. These atypical features are common in osteopetrosis tarda. The boy also had bilateral papilloedema, which has not been reported earlier in association with pycnodysostosis. Thus our case is a link between pycnodysostosis and osteopetrosis tarda indicating that these two disorders are related to each other in a manner more complex than the morphological similarity of increased bone density. Our case is an example of phenotypic heterogeneity in metabolic diseases.

The atypical features in our case warrant follow up for bone marrow failure, hypersplenism, and decreased visual acuity.

Final diagnosis

Pycnodysostosis with splenohepatomegaly, myelophthisic anaemia, and papilloedema.

Learning points

  • Pycnodysostosis is a rare genetic disorder of the skeletal system characterised by generalised osteosclerosis. The common clinical features are short stature, open cranial fontanelles, an obtuse mandibular angle, dysplastic clavicles, and short stubby hands and feet.

  • Osteopetrosis tarda (Albers-Schonberg disease) is another rare genetic disorder characterised by osteosclerosis. Anaemia, splenohepatomegaly, and neurological deficits like deafness and cranial nerve palsies are common findings.

  • Pycnodysostosis can rarely have visceral manifestations like anaemia, splenohepatomegaly, and neurological deficits like papilloedema.

  • Pycnodysostosis and osteopetrosis tarda are linked to each other in a manner more complex than the morphological similarity of increased bone density.


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