Brachycephaly, Deafness, Cataract, Microstomia, And Mental Retardation

Clinical Features

Fine and Lubinsky (1983) described a 2-year-old boy with psychomotor delay, brachycephaly, flat face, shallow orbits, hypertelorism, small mouth, cleft palate, cataract, deafness, rocker-bottom feet, and hypoplastic scrotum. Preus et al. (1984) studied a 23-month-old boy who exhibited developmental delay, sensorineural hearing loss, mild hypotonia, seizures, submucous cleft palate, and small nose, mouth, and ears. His nose also had a low root, flat bridge, and wide tip, and his ears were low set and posteriorly rotated with a thickened helix. Other features included unilateral cryptorchidism, tapered fingers with bilateral fifth-finger clinodactyly, and inverted left foot with prominent heel. Hand x-rays showed short metacarpals and phalanges of the second, third, and fourth digits, with the third digit most markedly foreshortened. Suthers et al. (1993) reported a 4-year-old boy with similar manifestations (without cleft palate) and abnormal chest (pectus carinatum superiorly and pectus excavatum inferiorly). The reported cases were sporadic.

Holder et al. (2007) reported an African American brother and sister with prominent frontal bones, flat facial profile, small nose, and developmental delay/mental retardation. Other anomalies included marked brachydactyly of fingers and toes, camptodactyly most severely affecting the second fingers, and hypoplastic/dystrophic nails. The boy also had craniosynostosis, microcephaly, shallow orbits, and poor dentition. The girl had sensorineural hearing loss, small mouth, thin upper lip, depressed nasal bridge, and low-set ears. Cytogenetic studies were normal.

Schoner et al. (2008) reported a female fetus at 24 weeks' gestation with Fine-Lubinsky syndrome. Prenatal ultrasound at 22 weeks' gestation showed polyhydramnios, growth retardation, and dysmorphic features including microcephaly, brachycephaly, extremely flat face, cataract, small nose, long philtrum, and microretrognathia, as well as rocker-bottom feet with syndactyly of the toes. Additional features seen on autopsy after elective termination of the pregnancy included narrow downslanting palpebral fissures, bilateral macrocornea, dorsally rotated simple ears, distinct microstomia with thin lips, Pierre-Robin anomaly with U-shaped cleft hard and soft palate, and glossoptosis. X-rays revealed shortening of the skull base, hypoplasia of the facial bones, short clavicles, bilateral costal defect, slender tubular bones, premature ossification centers in the tarsal bones, partial syndactyly of the right second to fourth toes, and deep-set, very short great toes. Schoner et al. (2008) tabulated the features of this patient as well as those of 6 previously reported patients with Fine-Lubinsky syndrome.

Corona-Rivera et al. (2009) reported a patient with Fine-Lubinsky syndrome and reviewed the clinical features of previously published patients. They identified key signs for diagnosis as nonsynostotic brachycephaly or plagiocephaly, structural brain anomalies, abnormal EEG, mental retardation, deafness, ocular abnormalities including cataracts or glaucoma, peculiar facies involving high/wide forehead, shallow orbits, flat/round face, low-set posteriorly rotated ears, and microstomia, and body asymmetry.

Inheritance

Corona-Rivera et al. (2009) noted that all 9 reported patients with Fine-Lubinsky syndrome were sporadic cases born of healthy parents, with reportedly normal karyotypes. However, several of these patients were later found to have a different disorder (see 601088).

Molecular Genetics

Exclusion Studies

Niceta et al. (2015) analyzed the MAF gene (177075) in the African American sibs previously reported by Holder et al. (2007) and in the female fetus described by Schoner et al. (2008) but did not find any mutations.