Journal of Genetic Disorders & Genetic Reports ISSN: 2327-5790

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Case Report, J Genet Disor Genet Rep Vol: 5 Issue: 2

Cleidocranial Dysplasia in a Mother and her New-born Daughter

Małgorzata Napieralska1, Aleksandra Modlinska2*, Tomasz Rybkiewicz1 and Regina Żuralska3
1Neonatal Intensive-Care Unit, Biegański Regional Specialist Hospital in Grudziadz, Dr Ludwik Rydygier street 15, postal code: 86-300 Grudziądz, Poland
2Department of Palliative Medicine, Medical University of Gdańsk, Dębinki Street 2, postal code: 80-208 Gdańsk, Poland
3Department of Community Nursing and Health Promotion, Faculty of Health Sciences with Sub faculty of Nursing and Institute of Maritime and Tropical Medicine. Medical University of Gdańsk, M. Skłodowskiej-Curie 3a street, postal code: 80-210 Gdańsk, Poland
Corresponding author : Dr. Aleksandra Modlinska
Department of Palliative Medicine, Medical University of Gdańsk, Poland, Debinki 2, 80-211 Gdańsk, Poland
Tel: +48 583491573
E-mail: [email protected]
Received: February 19, 2016 Accepted: May 28, 2016 Published: June 03, 2016
Citation: Napieralska M, Modlinska A, Rybkiewicz T, Żuralska R (2016) Cleidocranial Dysplasia in a Mother and her New-born Daughter. J Genet Disor Genet Rep 5:2. doi:10.4172/2327-5790.1000136


Cleidocranial dysplasia is a rare disease with an autosomal dominant inheritance pattern. Abnormalities caused by mutations in the short arm of chromosome 6 affect the skeletal system, mainly the scull, teeth, and clavicles. Symptom variability, from isolated anomalies to full disease manifestation, occurs even among members of the same family. The present work describes a case of disease manifestation in a mother and a newborn, both burdened with cleidocranial dysplasia.

Keywords: Cleidocranial dysplasia; Neonatal care; Hereditary disease


Cleidocranial dysplasia; Neonatal care; Hereditary disease


CCD (Cleidocranial Dysplasia) or Scheuthauer-Marie-Sainton syndrome is a rare disease with an autosomal dominant inheritance pattern (60-70%), but mutations also appear spontaneously in approx. 30-40% of cases [1-5]. CCD was described for the first time in 1897 by French physicians, Pierre Marie and R. Sainton. It was initially referred to as cleidocranial dysostosis [6]. The current name, CCD, has been used since 1967 [1,7].
CCD is a genetically conditioned disease with a wide range of expressions; core-binding factor subunit alpha-1 (CBFA1) mutations cause CCD and the heterozygous loss of function is sufficient to produce the disorder. The phenotype image is very diverse - from isolated dental anomalies to full disease manifestation. Variability occurs even among members of the same family.
This work presents a rare case of CCD in a new born child of a mother who was burdened with the same disorder.

Case Study

Case 1 – child
Female new born from the first pregnancy, born by cesarean section due to risk to the foetus on the 36th week of pregnancy. The child was in good general condition, exhibiting features of hypotrophy: body mass of 1700 g (below the 3rd centile), head circumference of 30 cm. The new born showed features of hypotonia, peripheral cyanosis, transient extremity tremor, and thermoregulatory disorders; no respiratory disorders were observed. The child remained in an incubator until the 8th day of life.
Physical examination by palpation revealed features of malformation of the scull bones with wide cranial sutures and large anterior and posterior fontanelles, 3 cm each (Figure 1), and a small, retracted mandible (Figure 2). Swelling of the hands and feet was observed.
Figure 1: Large fontanelles and wide sutures on palpation (delayed closure of the fontanelles).
Figure 2: Profile view (Case 1).
Additional examinations showed a slight reduction in blood platelets (132 G/ml), hyperbilirubinemia since the first day of life (7.4 mg/dl), and serological collision of the main blood types of the mother and child. Cerebrospinal fluid analysis was normal. Chest x-ray showed abnormal shape of the clavicles with a suspicion of congenital pseudarthrosis of the left clavicle (Figure 3). The malformations in scull structure were confirmed by an x-ray examination - visible open temporal and sagittal sutures; no Wormian bones were found.
Figure 3: Chest X-ray (PA view) of the newborn showing clavicular abnormalities.
Due to premature birth, the clinical condition of the child, and test results, antibiotic therapy (ampicillin, gentamicin) and phototherapy were implemented and continued until fourth day. Partial parenteral nutrition was applied together with gradually extended trophic feeding; enteral feeding was implemented subsequently. Breastfeeding and bottle-feeding were difficult due to the retracted mandible, so the new born was initially fed with the use of a nasogastric tube.
General Movements Assessment according to Prechtl was conducted at approximately one month of life, i.e. on the predicted, estimated normal date of birth. The video recording lasted 25 minutes; a 5 minute-long section was selected. The child’s movement patterns were at a normal level for the postnatal period. The girl calmly changed position and easily calmed down on her own. She reacted to the face of the person conducting the examination with facial expressions. She followed auditory stimuli with her eyes and head. Orofacial reflexes presented normal, quick, and lively reactions. The child failed a head control attempt (traction test in the neurologic examination) . In general assessment, the child exhibited disorders of muscle tone and head position asymmetry. There was a tendency to asymmetrical load of the head toward the right side. The child used the left side reluctantly, quickly returning to the preferred side. During passive position changes, when lied down on the left and right side, the infant extended the overstretched side and shortened the lightened side.
Taking into consideration the clinical picture of the child and the medical history of the girl’s mother, a suspicion of cleidocranial dysplasia (CCD) was put forward. Orthopaedic consultation revealed reduced muscle tone and increased internal rotation of both hip joints; the feet remained in normal position. An orthopaedist diagnosed hip dysplasia (Graf’s Ultrasound Class II A) and osteoarticular disorder and recommended further diagnostics. A neurology consultant confirmed the features of cleidocranial dysplasia. After discharge, further monitoring and care of a neonatologist, paediatrician and physiotherapist was recommended. Due to mother’s decision no genetic examinations were conducted until the day of presented publication.
Case 2 - Newborn’s mother
The family medical history was burdened with the presence of features of cleidocranial dysplasia in the mother. The woman was born by spontaneous labor. She achieved Apgar score of 9 at 1 minute and 10 at 5 minutes after birth. The neonatal period was uneventful. The development was considered normal. The incomplete medical documentation contained information concerning delayed fontanelle closure (4-5th year of life) and the concurrent diagnosis of pseudoarthrosis claviculae dextrae at the age of 6. She was hospitalized several times due to additional impacted teeth requiring surgical dental interventions. At the age of 11, the girl was hospitalized because of right facial nerve paralysis. Cleidocranial dysplasia has been confirmed by a radiological examination (hypoplasia of the right clavicle, persistent frontal suture, spina bifida Th1) and a dental consultation. No genetic examinations were conducted due to the limited capabilities available at the time. A medical examination at the age of 16 includes some anthropometric abnormalities. The height of the girl, 150 cm (less than the 3rd centile), and body mass of 58 kg (50- 75th c) were interpreted as overweight instead of dwarfism. Delayed bone ossification, short stature and increased head circumference with a characteristic scull shape were observed in the following years. The woman suffers from malformation of the right clavicle, dental defects, midfacial hypoplasia, and hypertelorism. Replacement of deciduous teeth by permanent teeth and numerous additional teeth still remain unresolved clinical problem.


Genetically conditioned ossification defects are at the basis of CCD. The disease is caused by a mutation in the gene on 6p21 encoding transcription factor CBFA1, i.e. runt-related transcription factor 2 (RUNX2) [4]. RUNX2 (CBFA1) is the only gene in which mutation is known to cause CCD. The RUNX2-related transcription factor is a regulator of bone formation [7-9]. This gene encodes a protein or a transcription factor required for dentinogenesis, differentiation of osteoblasts and maturation of chondrocytes, thus affecting intramembranous as well as endochondral ossification [3,10].
The incidence of CCD is the same for all ethnic groups, races, and both sexes; it occurs approx. once per 1 million births [1,3,5]. The subsequent generations with inherited CCD exhibit relatively milder forms of the disease [3]. The majority of cases are diagnosed - like in the presented case of the child’s mother - during childhood or adolescence, and clinical symptoms vary in intensity. Over 84% of patients exhibit the discussed skeletal symptoms, including maxillary hypoplasia and defects of the clavicle [11]. Delayed closure of the fontanelle and cranial sutures in children and adolescents as well as increased arm mobility in all age groups (ability to move the shoulders close together) are important clinical diagnostic features of CCD [3,9,10].
Even though diagnosis is possible as early as in the 2nd trimester of the prenatal period, it is usually difficult, delayed, or not performed at all due to the ambiguous and diverse phenotypic traits [1,3,5,6]. The phenotype image is very diverse - from isolated dental anomalies to full disease manifestation. Variability occurs even among members of the same family. The patients are usually diagnosed, like in the discussed cases, based on their short stature, clavicular hypoplasia, open fontanelles, and dental disorders [12]. The periods of the highest symptom expression are childhood and adolescence, but characteristic features are present as early as in the neonatal period.
The neonate (Case 1) exhibited phenotypic traits characteristic of CCD. The image of the foetus in prenatal ultrasound was normal, but examinations conducted on individuals burdened with CCD usually reveal hypo mineralization with hypoplasia of the clavicles and/or the scull [3]. The prematurely born girl exhibited features of hypotrophy as well as scull ossification and clavicle development disorders. In the neonatal period, head circumference in children with CCD is usually similar to healthy neonates; however, a deformation occurring during birth as a result of the soft, calcium-deficient scull is a characteristic feature [3,13]. Scull examination shows features of brachycephaly, open fontanelles or their delayed closure, presence of open cranial sutures with visibly bulging frontal and temporal bones resulting from numerous extra bone pieces (Wormian bones) on the circumference of occipital, parietal, and frontal bones [2,13,14]. Scull x-ray of the presented girl did not reveal any Wormian bones, but open temporal and sagittal sutures were visible. The most common craniofacial defects are hypoplasia of the middle section of the face, depressed nasal bridge, high-arched palate, and, like in the case of the child described above, maxillary hypoplasia [14]. The majority of craniofacial defects become clearly visible during adolescence [7].
The clinical presentation of the woman (Case 2) also included delayed bone ossification, hypoplasia of the right clavicle, as well as dental and craniofacial defects. Disorders of the oral cavity constitute one of the main functional and esthetic causes of patient complaints; dental disorders are a characteristic feature of the disease [2,4,8]. Additional teeth and eruption disorders affect approximately 94% of CCD patients [11]. Impacted deciduous teeth, delayed eruption of permanent teeth, and the presence of a large number of impacted additional teeth result in insufficient space between the teeth in the oral cavity and lead to malocclusion [2,15]. A dentist or an orthodontist is frequently the first specialist visited by a patient when worried about delayed teeth eruption or lack of permanent teeth [2,15]. Disorders in deciduous teeth replacement by permanent teeth and numerous additional teeth were the cause of many dental interventions in the discussed case as well (Case 2). The incomplete, subsequent anthropometric examinations pointed to the short stature (below the 3rd centile) and increased head circumference with characteristic scull shape. Defects and ossification disorders of the pelvis constitute an indication for cesarean section in over 50% of women with CCD [5]. The presented new born (Case 1) was also born by cesarean section, but the indications did not include cephalo-pelvic disproportion or any other maternal indications.
CCD is characterized by radiologically confirmed aplasia (10% of cases) or hypoplasia of one (Case 2) or both (Case 1) clavicles [3,12,15]. The absence or hypoplasia of the clavicles in ultrasound, if no other symptoms suggesting other skeletal dysplasias are present, should be considered indicative of CCD [5,9]. A survey study conducted by van Tongel et al. among 36 adult Belgians suffering from CCD provided very interesting results [12]. Despite the fact that 17 patients exhibited complete, bilateral absence of the clavicles, 16 patients - bilateral partial absence, and 3 patients - complete absence on one side and partial on the other, they did not differ in terms of the efficiency of their shoulder girdle in subjective assessment [12]. The neck is usually long and narrow, while the shoulders are visibly lowered. Diagnosis may be facilitated by the assessment of long bone growth in relation to the size of the clavicle. Ossification disorders of the bones forming from connective tissue base, including endochondral ossification, usually lead to height deficiency, but is usually not associated with a disproportionate stature [10]. Less frequent features include hypertelorism, spinal curvature, spina bifida, varus or valgus knees or hips, wide pubic symphysis, ossification disorders of metacarpal and metatarsal bones, as well as hearing disorders [2,10,15]. The psychomotor development of CCD patients is normal in the majority of cases, but there are reports of mental retardation associated with CNS defects [3,9].


Characteristic clinical features, family history, and radiological examination results usually enable to establish a highly probable preliminary diagnosis and to refer the patient for further diagnostics, including genetic tests. CCD patients require the care of an interdisciplinary team and cooperation of different specialists. Orthopaedic monitoring, rehabilitation, as well as orthodontic and dental care reduce the consequences for the skeletal system, and early diagnosis is necessary for the selection of an optimum plan and the achievement of therapeutic benefits improving the quality of life of CCD patients.


The authors would like to thank Neonatal Intensive-Care Unit staff for help with this case.


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