Fine-Lubinsky syndrome

The signs and symptoms known to occur in people with Fine-Lubinsky syndrome (FLS) are based on reports of the few people who have been diagnosed and described in the medical literature. Numerous features have been reported and many of them vary among affected people. The key signs for diagnosis may include:

• non-synostotic brachycephaly or plagiocephaly (a deformity of the skull that is not due to bone fusion)
• structural brain anomalies
• abnormal electroencephalogram (EEG)
• intellectual disability
• deafness
• ocular (eye) abnormalities (cataracts or glaucoma)
• distinctive facial features (including a high/wide forehead; shallow eye orbits; a flat/round face; low-set, posteriorly-rotated ears; and an abnormally small mouth)
• body asymmetry, which may be present at birth (congenital)^[3]

The cause of Fine-Lubinsky syndrome remains unknown. With the exception of one family report of an affected brother and sister (suggesting an autosomal recessive inheritance pattern), all other cases have been sporadic (occurring in people with no family history of FLS). Additional reports are needed to identify a possible genetic cause of FLS. While karyotypes (pictures of chromosomes) were reportedly normal in affected people, the presence of a very small chromosomal rearrangement (too small to detect with a karyotype) as a possible cause for FLS has not been ruled out.^[4][3]

Almost all people reported to have Fine–Lubinsky syndrome (FLS) have been the only affected people in their families (these cases were sporadic). There has been one report of an affected brother and sister with unaffected parents, suggesting autosomal recessive inheritance.^[5][3] Additional reports are needed to identify a possible genetic cause for the condition.^[3] Parents of a child with FLS should be aware that if the condition is inherited in an autosomal recessive manner, each of their children has a 25% (1 in 4) risk to be affected. Although karyotypes (pictures of chromosomes) have been reported as normal in affected people, the presence of a very small chromosomal rearrangement has not been excluded as a possible cause of FLS.^[3]

In 2009, Corona-Rivera et. al reviewed the signs and symptoms reported in people diagnosed with Fine-Lubinsky syndrome (FLS). They identified key signs for diagnosis as: non-synostotic (without synostosis) brachycephaly (short or broad head) or plagiocephaly (flattening of the head); structural brain anomalies; abnormal EEG; intellectual disability; deafness; ocular (eye) abnormalities including cataracts or glaucoma; distinctive facial features involving high/wide forehead, shallow orbits, flat/round face, low-set posteriorly rotated ears, and microstomia (small mouth); and body asymmetry.^[6]

Due to the rarity of Fine-Lubinsky syndrome (FLS) and the few available reports in the medical literature, the long-term outlook for people with FLS is not well known. People diagnosed with FLS have a variety of signs and symptoms, so the prognosis likely varies depending on the specific symptoms present and the severity in each person.

To our knowledge, the vast majority of reports describe young children less than 2 years of age. However, there is a report of a male with features suggestive of FLS last examined at age 11 (in 1997), and a report of a female last examined at age 20.

The 11 year old male had a long history of dental problems and failed multiple hearing screens throughout childhood, yet a reevaluation at age 9 suggested his hearing was in the normal range. At 11 years old, he had short stature, a small head (microcephaly), and various craniofacial and skeletal findings. He reportedly attended special education classes at the elementary school level. He was able to speak in full sentences and follow multiple-step commands, but his speech was sometimes unintelligible to non-family members.^[7]

The 20 year old female was first seen at 6 months of age and then again at 7.5 years of age. By her 2nd visit her facial features had reportedly changed and had become asymmetric. She had various features including skeletal abnormalities, a history of a cataract and severe deafness, and dental abnormalities. At age 14 she had 22 teeth, was short, and her developmental delay was more obvious. She could read and write but was unable to attend a normal school and her behavior was reportedly immature. At age 20, her distinctive facial features were unchanged, and she had underdeveloped and low-set breasts. She could read and write phonetically but could not understand grammar.^[8]

We are not aware of additional reports in the literature that describe people with FLS later in adulthood; therefore, we do not have information about whether affected people are at risk for new health problems as they age or what the life expectancy might be.