*Center for Human Genetics; **Department of Obstetrics and Gynecology and ***Department of Neonatology , University of Leuven, Leuven, Belgium.

Address correspondence to Ingrid Witters, Center for Human Genetics, Herestraat 49, 3000 Leuven, Belgium

Synonyms

Oral-Facial-Digital syndrome type IV (OFD 4; 258860), OFD syndrome, Baraitser-Burn type, OFD syndrome with tibial defects, Baraitser-Burn syndrome.

Definition

Mohr syndrome (OFD2; 252100) is characterized by poly-, syn-, and brachydactyly, lobate tongue with papilliform protuberances, angular form of the alveolar process of the mandible.
Majewski syndrome (Short-Rib-Polydactyly type II; 263520) is characterized by a small thorax with short ribs, and polydactyly.
The Mohr-Majewski compound combines features of OFD2 and Majewski syndrome. It is not yet clear whether this is to be considered as a separate entity or a variable expression of the OFD group (as described in the OFD type IV syndrome) or of the Short-Rib-Polydactyly syndromes.

Case report

A consanguineous Turkish couple, with one healthy daughter, was seen in the second pregnancy at 25 weeks for a fetal skeletal dysplasia with a small, long thorax and mesomelic shortening of the limbs, no polydactyly, and a normal amount of amniotic fluid (fig. 1 ultrasound; fig. 2, MRI).
Karyotype was normal 46, XX.
The parents decided to continue the pregnancy. At 39 weeks the girl was born by caesarean section for fetal distress (weight: 2630 g - 5th centile; length: 47 cm - 5-10th centile; head circumference: 35.4 cm - 90th centile).
On postnatal examination she has a small thorax, short limbs (mainly the lower legs and upper arms), short hands and feet (fig. 8, 9, 10). On her tongue she has two hamartomas (fig. 7). They were removed surgically. She has an irregular alveolar ridge and bilateral retinal colobomas. X-rays show a small long thorax with short ribs (fig. 5, 6), mesomelic shortening of the limbs, short phalanges (fig. 2, 3, 4, 5) and broader metaphyses of the tibiae and femora.
At the age of 10 months she has a developmental score for 2 months, is severely hypotonic and requires tube feeding. Hearing examination (Brainstem Evoked Response Audiometry - BERA) shows no abnormalities. Brain MRI shows no abnormalities.

Figure 1: Prenatal ultrasound with small, long thorax.

Figure 2: Prenatal MRI (25 weeks) with small thorax, short limbs, normal amount of amniotic fluid.

Prenatal videos 1, 2: Normal facial profile with visible polyhydramnios; hyperextension of the fetal head.

Prenatal videos 3, 4: Narrow thorax.

Prenatal videos 5, 6: Short appearance of the fetal legs.

Figures 2, 3, 4, 5, and 6: Postnatal radiograms.

Pictures 7, 8, 9, and 10: Postnatal appearance of the baby - note hamartomas of the tongue, narrow thorax, brachydactyly.

Etymology

The Orofaciodigital syndromes (OFD) are a group of conditions sharing oral, facial and digital anomalies. The classification of OFD is based on the phenotype and the mode of inheritance and counts at least 11 different types. Baraitser suggested the existence of the OFD syndrome type IV, combining features of Majewski type II, Short-Rib-Polydactyly syndrome and Mohr syndrome (OFD type II). The Short-Rib-Polydactyly syndromes (SRPS) are a group of skeletal dysplasias manifested by short-limb dwarfism, short ribs with thoracic dysplasia and polydactyly and counts 4 different types (type I: Saldino-Noonan; type II: Majewski; type III: Naumoff; type IV: Beemer-Langer) with considerable overlap in phenotype and radiological features. Polydactyly is often present, but is not obligatory.

Etiology

The Mohr-Majewski compound (OFD type IV) is an autosomal recessive condition.

Pathogenesis

No genes are known yet to further examine whether Mohr-Majewski syndrome is a separate entity or a variable expression of OFD group of syndromes or the Short-rib polydactyly syndromes.

Sonographic findings

The Mohr-Majewski compound (OFD type IV)
- short ribs
- micromelia, short broad tibiae
- cleft lip/palate
- pre- postaxial polydactyly

Implications for targeted examinations

The present patient shows features of Mohr syndrome (tongue hamartomas, irregular alveolar ridge, short hands with brachydactyly) and of Majewski syndrome (small thorax with short ribs, short limbs) but no polydactyly.

The prenatal ultrasound examination was dominated in the present case by the presence of a small thorax and short limbs without polydactyly.

Differential diagnosis

Regarding the prenatal diagnosis of small thorax and short limbs:

• Majewski syndrome; SRPS type II (263520): Small thorax, short ribs, short limbs, polydactyly (pre-and postaxial). Radiological appearance: deficient vertebral ossification, metaphyseal dysplasia, disproportionate shortening of the tibia, normal pelvis;
• Ellis-van Creveld syndrome (225500): narrow chest, short ribs, short limbs, postaxial polydactyly of hands. Radiological appearance: short long bones, smooth rounded metaphyses, vertically short iliac bones, horizontally orientated acetabula with medial/lateral spikes, short ribs, normal vertebrae. Cardiovascular malformations, partial harelip;
• Jeune syndrome (208500): Asphyxiating thoracic dysplasia with narrow long thorax. Radiologically as Ellis-van Creveld but with irregular metaphyses. Polydactyly of hands and feet. Polycystic kidneys with hepatopancreatic fibrosis.

Associated anomalies:

• Mohr syndrome (OFD II):
  Conductive hearing loss;
  Hypertelorism, telecanthus, low nasal bridge, bifid nasal tip;
  Hypertrophied frenula, midline cleft of tongue, tongue nodules, lobulate tongue, high-arched palate, cleft palate, midline cleft lip;
  Absent central incisor;
  Pectus excavatum;
  Wormian bones skull, maxillary hypoplasia;
  Scoliosis;
  Metaphyseal flaring, metaphyseal irregularity;
  Bilateral preaxial polydactyly feet, postaxial polydactyly hands, short hands, fifth finger clinodactyly, brachydactyly, syndactyly;
  Bilateral preaxial polydactyly, partial duplication of hallux, broad cuboid first metatarsal, extra cuneiform bone;
  Porencephaly, hydrocephaly.

• Majewski syndrome (SRPS II):
  Lethal dwarfism identifiable at birth;
  Median cleft lip, cleft-plate;
  Hypoplastic epiglottis, malformed larynx, pulmonary hypoplasia;
  Short ribs;
  Gastrointestinal atresia;
  Ambiguous genitalia, genitourinary atresia, polycystic kidneys, glomerular and renal tubular cysts;
  Pre-postaxial polydactyly, micromelia, hallucal and postaxial polysyndactyly of the feet;
  Pachygyria, hypoplastic cerebellar vermis;
  Hydrops fetalis.

• The Mohr-Majewski compound (OFD IV):
  Short stature;
  Micrognathia, low-set ears;
  Hypertelorism, epicanthal folds;
  High-arched palate, cleft palate, lobulated tongue, tongue nodules, oral frenula;
  Pectus excavatum;
  Short tibiae;
  Preaxial and/or postaxial polydactyly, Brachydactyly, Clinodactyly of hands/feet;
  Cerebral atrophy, porencephaly.

Prognosis

• Patients with Mohr syndrome have normal intelligence in the majority of cases.
• Majewski syndrome is a lethal skeletal dysplasia.
• In cases of the ‘Mohr-Majewski compound' the prognosis is mainly determined by the presence of lung hypoplasia, and cerebral malformations.

Recurrence risk

The Mohr-Majewski compound is an autosomal recessive condition

Management

If on ultrasound a skeletal dysplasia with small thorax is visualized before viability, termination of pregnancy should be offered to the parents.

References